Trial Outcomes & Findings for A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Including a Placebo-Treated Non-Carrier Cohort (NCT NCT01998841)

Results Overview

API ADAD Composite Cognitive Test is a combination of tests, most sensitive to detect cognitive decline \& progression. API ADAD Composite Cognitive Test total score were computed from: Consortium to Establish a Registry for AD (CERAD) Word List: Recall (score range=0-10); Multilingual Naming Test (score range=0-15); Mini-Mental State Examination (MMSE) for orientation to time (score range=0-5); CERAD Constructional Praxis (measure of visuospatial ability) (score range=0-11); Raven's Progressive Matrices (measure of nonverbal fluid reasoning \& visuospatial abilities), Set A (score range=0-12). ADAD-API Cognitive Composite Test total score = \[(Multilingual Naming Test Score/15)+(MMSE Score/5)+(Raven's Progressive Matrices Score/12)+(CERAD Word List Recall Score/10)+(CERAD Constructional Praxis Score/11)\]\*20. Total score ranges=0-100. Higher score=better results. Annualized rate of change in API ADAD Composite Cognitive Test was estimated using random coefficient regression model.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

252 participants

Primary outcome timeframe

Baseline up to approximately Week 416

Results posted on

2024-07-30

Participant Flow

Participants who were carriers and non-carriers of presenilin 1 (PSEN1) E280A mutation of autosomal-dominant Alzheimer's disease (ADAD) took part in the study at four investigative sites in Colombia from 20 December 2013 to 08 August 2023.

252 participants were enrolled to receive their assigned treatment. Study consisted of 2 periods: Study Period A \& B. Participants who completed Study Period A had an option to continue treatment in Study Period B. 74 participants from Crenezumab - Mutation Carriers arm, 73 from Placebo - Mutation Carrier arm, and 72 from Placebo - Non-Carriers of Mutation arm choose to continue treatment in Period B.

Participant milestones

Participant milestones
Measure	Study Period A: Crenezumab - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 milligrams (mg), subcutaneously (SC), every two weeks (Q2W), or 60 milligrams per kilograms (mg/kg), intravenously (IV), every four weeks (Q4W), for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carrier Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo SC, Q2W, or IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Non-Carriers of Mutation Participants who were non-carriers of PSEN1 E280A mutation, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Study Period B: Crenezumab Participants who were PSEN1 E280A mutation carriers and who completed treatment with crenezumab or placebo in Period A were given an option to continue receiving crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in Period B for up to 51 weeks.	Study Period B: Placebo Participants who were non-carriers of PSEN1 E280A mutation and who received crenezumab matching placebo in Period A were given the option to continue receiving crenezumab matching placebo SC, Q2W or IV, Q4W in Study Period B, for up to 51 weeks.
Study Period A STARTED	85	84	83	0	0
Study Period A COMPLETED	79	78	80	0	0
Study Period A NOT COMPLETED	6	6	3	0	0
Study Period B STARTED	0	0	0	147	72
Study Period B COMPLETED	0	0	0	140	70
Study Period B NOT COMPLETED	0	0	0	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Study Period A: Crenezumab - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 milligrams (mg), subcutaneously (SC), every two weeks (Q2W), or 60 milligrams per kilograms (mg/kg), intravenously (IV), every four weeks (Q4W), for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carrier Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo SC, Q2W, or IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Non-Carriers of Mutation Participants who were non-carriers of PSEN1 E280A mutation, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Study Period B: Crenezumab Participants who were PSEN1 E280A mutation carriers and who completed treatment with crenezumab or placebo in Period A were given an option to continue receiving crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in Period B for up to 51 weeks.	Study Period B: Placebo Participants who were non-carriers of PSEN1 E280A mutation and who received crenezumab matching placebo in Period A were given the option to continue receiving crenezumab matching placebo SC, Q2W or IV, Q4W in Study Period B, for up to 51 weeks.
Study Period A Reason Not Disclosed to Prevent Genetic Unblinding	6	6	3	0	0
Study Period B Reason Not Disclosed to Prevent Genetic Unblinding	0	0	0	7	2

Baseline Characteristics

A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Including a Placebo-Treated Non-Carrier Cohort

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Period A: Crenezumab - Mutation Carrier n=85 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Non-Carriers of Mutation n=83 Participants Participants who were non-carriers of PSEN1 E280A mutation, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Total n=252 Participants Total of all reporting groups
Age, Continuous	36.8 years STANDARD_DEVIATION 5.3 • n=5 Participants	36.9 years STANDARD_DEVIATION 6.3 • n=7 Participants	43.3 years STANDARD_DEVIATION 7.2 • n=5 Participants	39.0 years STANDARD_DEVIATION 7.0 • n=4 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	59 Participants n=7 Participants	57 Participants n=5 Participants	160 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants	92 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	85 Participants n=5 Participants	84 Participants n=7 Participants	83 Participants n=5 Participants	252 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	6 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized White	37 Participants n=5 Participants	40 Participants n=7 Participants	35 Participants n=5 Participants	112 Participants n=4 Participants
Race/Ethnicity, Customized More than one race	25 Participants n=5 Participants	24 Participants n=7 Participants	33 Participants n=5 Participants	82 Participants n=4 Participants
Race/Ethnicity, Customized Others	13 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	37 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately Week 416

Population: Modified Intent-to-Treat (mITT) population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

API ADAD Composite Cognitive Test is a combination of tests, most sensitive to detect cognitive decline \& progression. API ADAD Composite Cognitive Test total score were computed from: Consortium to Establish a Registry for AD (CERAD) Word List: Recall (score range=0-10); Multilingual Naming Test (score range=0-15); Mini-Mental State Examination (MMSE) for orientation to time (score range=0-5); CERAD Constructional Praxis (measure of visuospatial ability) (score range=0-11); Raven's Progressive Matrices (measure of nonverbal fluid reasoning \& visuospatial abilities), Set A (score range=0-12). ADAD-API Cognitive Composite Test total score = \[(Multilingual Naming Test Score/15)+(MMSE Score/5)+(Raven's Progressive Matrices Score/12)+(CERAD Word List Recall Score/10)+(CERAD Constructional Praxis Score/11)\]\*20. Total score ranges=0-100. Higher score=better results. Annualized rate of change in API ADAD Composite Cognitive Test was estimated using random coefficient regression model.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in the Autosomal-Dominant Alzheimer's Disease (API ADAD) Composite Cognitive Test Total Score	-1.10 points on scale per year Standard Error 0.29	-1.42 points on scale per year Standard Error 0.29

PRIMARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

FCSRT assesses immediate \& delayed verbal episodic memory, using Controlled Learning to optimize encoding specificity for more effective recall. Participants were to remember a list of 16 items presented on cards. Participant's task was to learn \& attempt a free recall of the items, followed by a semantically cued recall of items not spontaneously produced during free recall. There were a total of three learning trials, each preceded by 20 seconds of interfering cognitive task. For first two trials, participants were reminded of any item not recalled in cued recall. Free recall (score range: 0-48) \& cued recall (score range: 0-64) assessment occurred immediately, after each of three learning trials, \& after a delay of approx. 30 minutes. Higher scores indicate better performance. FCSRT Cueing Index=(FCSRT Total Free Recall score-FCSRT Total Recall score)/(FCSRT Total Free Recall score-48). Score range for FCSRT Cueing Index is 0-1, with higher score=better results.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in an Episodic Memory Measure: Free and Cued Selective Reminding Task (FCSRT) Cueing Index	-0.03 points on scale per year Standard Error 0.004	-0.04 points on scale per year Standard Error 0.004

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Time to progression was calculated from the time at baseline to first confirmed diagnosis of progression from preclinical AD to MCI or from preclinical AD to dementia due to AD whichever occurred first. Preclinical AD was defined as participants who were at certain risk of developing AD dementia but did not have overt symptoms and did not meet criteria for MCI or dementia.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Time to Progression From Preclinical AD to Mild Cognitive Impairment (MCI) Due to AD or From Preclinical AD to Dementia Due to AD	NA days Median, upper and lower limit of 95% confidence interval (CI) were not estimable due to insufficient number of participants with events.	NA days Interval 2622.0 to Median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Time to progression was defined as the time at baseline to first increase in the CDR global score i.e., score of \> zero on the CDR Global scale. The standard CDR global scale describes five degrees of impairment in performance on each of six categories of cognitive functioning, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the six categories of function was synthesized into one global rating of dementia with a score ranging from 0 to 3 (0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia). A higher score indicates a greater degree of impairment.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Time to Progression to Non-zero in CDR Scale Global Score	2759.0 days Interval 2391.0 to Upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA days Interval 2395.0 to Median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

The CDR-SB is a rater administered scale and impairment is scored in the following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. Annualized rate of change in CDR Scale - SOB was calculated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in the CDR Scale - Sum of Boxes (SOB)	0.30 points on scale per year Standard Error 0.06	0.33 points on scale per year Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

RBANS is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS comprised of 12 subtests which generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. RBANS Total Score = Index Score based on the (Index Score for Immediate Memory + Index Score for Visuospatial/Constructional + Index Score for Language + Index Score for Attention + Index Score for Delayed Memory). Index scores and total scores range from 40-160. A higher score indicates better cognitive functioning. Annualized rate of change in RBANS was calculated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in a Measure of Overall Neurocognitive Functioning: RBANS	-0.23 points on scale per year Standard Error 0.21	-0.40 points on scale per year Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Amyloid deposition in brain is one of the defining neuropathologic findings of AD. Cerebral amyloid burden \& effect of crenezumab on cerebral amyloid were assessed using 18F- Florbetapir PET. Florbetapir exhibits high affinity specific binding to amyloid plaques, which allows for a measurement of the relative amyloid burden as the ratio of the standard uptake values (SUVR) in a cortical composite region of interest (including the frontal, temporal, parietal, and cingulate cortices with a subcortical white matter reference region). Annualized rate of change in cerebral fibrillar amyloid accumulation was calculated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in Mean Cerebral Fibrillar Amyloid Accumulation Using Florbetapir Positron Emission Tomography (PET)	0.017 SUVR per year Standard Error 0.001	0.017 SUVR per year Standard Error 0.001

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Regional CMRgl and the effect of crenezumab on regional CMRgl was assessed using FDG-PET. FDG PET evaluates the regional brain metabolic rates for glucose as a sensitive, in vivo metabolic index of brain function. Regional CMRgl was derived from FDG PET images using an empirically predefined statistical ROI (sROI) known to be preferentially affected by CMRgl decline in participants with AD. Results are reported as standardized uptake value ratios. Annualized rate of change in CMRgI was calculated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in Regional Cerebral Metabolic Rate of Glucose (CMRgI) Using Fluorine-18-Labeled 2-Deoxyglucose (FDG)-PET in a Predefined ROI	-0.012 SUVR per year Standard Error 0.002	-0.015 SUVR per year Standard Error 0.002

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Cerebral atrophy correlates closely with the gradual cognitive decline in AD and can be visualized by MRI. The change in brain atrophy after treatment with crenezumab was measured by volumetric measurements using MRI which measures volumes of the key brain structures-hippocampus, ventricles, and other brain structures-and compares the volumes to standard norms based on the age, gender and cranial volume. The regions of interest for atrophy measurement included whole brain, bilateral hippocampus, and bilateral ventricles. The annualized rate of change in brain atrophy was calculated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in Brain Atrophy Measured by Volumetric Measurements Using Magnetic Resonance Imaging (MRI) Whole Brain	-721.91 cubic millimeter (mm^3)/year Standard Error 65.33	-829.69 cubic millimeter (mm^3)/year Standard Error 65.42
Period A: Annualized Rate of Change in Brain Atrophy Measured by Volumetric Measurements Using Magnetic Resonance Imaging (MRI) Bilateral Hippocampus	-92.62 cubic millimeter (mm^3)/year Standard Error 12.25	-102.22 cubic millimeter (mm^3)/year Standard Error 12.27
Period A: Annualized Rate of Change in Brain Atrophy Measured by Volumetric Measurements Using Magnetic Resonance Imaging (MRI) Bilateral Ventricles	808.16 cubic millimeter (mm^3)/year Standard Error 150.14	788.25 cubic millimeter (mm^3)/year Standard Error 150.29

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoint.

CSF biomarker tTau has been considered as a general marker of neurodegeneration. CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific pTau species, is thought to be a marker for progressive cellular degeneration in AD. Annualized rate of change in tTau and pTau was estimated using RCRM.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=48 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=42 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in Tau-Based Cerebral Spinal Fluid (CSF) Biomarkers (Total Tau (tTau) and Phospho-tau (pTau) tTau	4.91 picograms per milliliters (pg/mL)/year Standard Error 2.16	6.88 picograms per milliliters (pg/mL)/year Standard Error 2.19
Period A: Annualized Rate of Change in Tau-Based Cerebral Spinal Fluid (CSF) Biomarkers (Total Tau (tTau) and Phospho-tau (pTau) pTau	0.84 picograms per milliliters (pg/mL)/year Standard Error 0.32	1.34 picograms per milliliters (pg/mL)/year Standard Error 0.33

SECONDARY outcome

Timeframe: From Baseline up to approximately Week 416

Population: Safety population included all randomized participants who received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. An SAE is any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s); considered a significant medical event by the investigator. Pooled data has been reported for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=251 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants with SAEs	56 Participants	—
Period A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants with AEs	251 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to approximately Week 416

Population: Safety population included all randomized participants who received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Participants who withdrew from the study due to AEs are reported here. Pooled data has been reported for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=251 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Number of Participants Who Withdrew From the Study Treatment Due to AEs	1 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to approximately Week 416

Population: Safety population included all randomized participants who received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status.

AE=any unfavorable \& unintended sign, symptom/disease temporally associated with use of an investigational product/other protocol-imposed intervention, regardless of attribution. Amyloid-related imaging abnormalities (ARIA)=spectrum of image abnormalities detected on MRI. Two types of ARIAs reported are: Amyloid-related Imaging Abnormalities-Edema/Effusion (ARIA-E)=MRI alterations thought to represent vasogenic edema (VE) \& related extravasated fluid phenomena, \& Amyloid-related Imaging Abnormalities-Hemosiderin Deposition (ARIA-H)=MRI alterations attributable to microhemorrhages (microbleeds \[MBs\]) \& leptomeningeal hemosiderosis. Cerebral macrohemorrhages were read on MRI scans. Occurrence of pneumonia were verified by imaging (e.g., chest X-ray). Other AESIs were drug induced liver injury \& suspected transmission of infectious agent via medicinal products. Pooled data has been reported for this outcome measure to maintain blinding of participant's mutation status \& treatment group.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=251 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) ARIA-H	6 Participants	—
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) ARIA-E	1 Participants	—
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) Cerebral Macrohemorrhage	0 Participants	—
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) Drug Induced Liver Injury	1 Participants	—
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) Suspected Transmission of Infectious Agents via a Medicinal Product	0 Participants	—
Period A: Number of Participants With Adverse Events of Special Interest (AESIs) Pneumonia	0 Participants	—

SECONDARY outcome

Timeframe: Baseline (Day 1) up to approximately Week 416

Population: Safety population included all randomized participants who received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Infusion and injection-related reactions were defined as any AEs that occurred during or within 24 hours after the study drug injection or infusion. Pooled data has been reported for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=251 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Number of Participants Injection Reactions and Infusion-related Reaction (IRRs) Injection Reaction	92 Participants	—
Period A: Number of Participants Injection Reactions and Infusion-related Reaction (IRRs) Infusion Related Reaction	70 Participants	—

SECONDARY outcome

Timeframe: Baseline up to approximately Week 260

Population: Safety population included all randomized participants who received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status.

The number of participants with positive results for ADA against crenezumab at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" during the study period. Treatment-induced ADA = a participant with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Number of Participants With Anti-Crenezumab Antibodies	5 Participants	—

SECONDARY outcome

Timeframe: Predose: Baseline (Day 1), Weeks 104 and 260; early termination visit and unscheduled visit (up to approximately Week 416)

Population: PK-evaluable population included all safety-evaluable participants with at least 1 plasma sample, provided sufficient dosing information (dose and dosing time) is available. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=36 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration Baseline (Day 1)	NA micrograms per milliliters (µg/ml) Geometric Coefficient of Variation NA The data was not evaluable as the samples were below lower limit of quantification (BLLQ).	—
Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration Week 104	0.198 micrograms per milliliters (µg/ml) Geometric Coefficient of Variation 81.6	—
Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration Week 260	0.311 micrograms per milliliters (µg/ml) Geometric Coefficient of Variation 214.6	—
Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration Early Termination Visit	0.238 micrograms per milliliters (µg/ml) Geometric Coefficient of Variation 190.4	—
Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration Unscheduled Visit	2.23 micrograms per milliliters (µg/ml) Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 12, 16, 17, 26, 38, 52, 78, 104, 128, 130, 156, 180, 182, 208, 232, 234, 260, 284, 312, 336, 364, 388, early termination visit and unscheduled visit (up to approximately Week 416)

Population: PK-evaluable population included all safety-evaluable participants with at least 1 plasma sample, provided sufficient dosing information (dose and dosing time) is available. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Serum Crenezumab Concentration Baseline (Day 1)	NA µg/ml Geometric Coefficient of Variation NA The data was not evaluable as the samples were BLLQ.	—
Period A: Serum Crenezumab Concentration Week 4	69.2 µg/ml Geometric Coefficient of Variation 39.1	—
Period A: Serum Crenezumab Concentration Week 12	93.9 µg/ml Geometric Coefficient of Variation 51.8	—
Period A: Serum Crenezumab Concentration Week 16	85.8 µg/ml Geometric Coefficient of Variation 37.2	—
Period A: Serum Crenezumab Concentration Week 17	114 µg/ml Geometric Coefficient of Variation 37.3	—
Period A: Serum Crenezumab Concentration Week 26	96.5 µg/ml Geometric Coefficient of Variation 86.3	—
Period A: Serum Crenezumab Concentration Week 38	98.0 µg/ml Geometric Coefficient of Variation 121.6	—
Period A: Serum Crenezumab Concentration Week 52	82.9 µg/ml Geometric Coefficient of Variation 285.3	—
Period A: Serum Crenezumab Concentration Week 78	75.9 µg/ml Geometric Coefficient of Variation 777.0	—
Period A: Serum Crenezumab Concentration Week 104	86.2 µg/ml Geometric Coefficient of Variation 680.2	—
Period A: Serum Crenezumab Concentration Week 128	124 µg/ml Geometric Coefficient of Variation 28.6	—
Period A: Serum Crenezumab Concentration Week 130	72.3 µg/ml Geometric Coefficient of Variation 1514.9	—
Period A: Serum Crenezumab Concentration Week 156	80.7 µg/ml Geometric Coefficient of Variation 1445.4	—
Period A: Serum Crenezumab Concentration Week 180	56.1 µg/ml Geometric Coefficient of Variation 3140.6	—
Period A: Serum Crenezumab Concentration Week 182	85.5 µg/ml Geometric Coefficient of Variation 1135.4	—
Period A: Serum Crenezumab Concentration Week 208	94.3 µg/ml Geometric Coefficient of Variation 983.0	—
Period A: Serum Crenezumab Concentration Week 232	69.4 µg/ml Geometric Coefficient of Variation 3990.1	—
Period A: Serum Crenezumab Concentration Week 234	62.3 µg/ml Geometric Coefficient of Variation 2724.2	—
Period A: Serum Crenezumab Concentration Week 260	101 µg/ml Geometric Coefficient of Variation 1417.7	—
Period A: Serum Crenezumab Concentration Week 284	131 µg/ml Geometric Coefficient of Variation 690.6	—
Period A: Serum Crenezumab Concentration Week 312	116 µg/ml Geometric Coefficient of Variation 645.0	—
Period A: Serum Crenezumab Concentration Week 336	117 µg/ml Geometric Coefficient of Variation 544.7	—
Period A: Serum Crenezumab Concentration Week 364	227 µg/ml Geometric Coefficient of Variation 38.2	—
Period A: Serum Crenezumab Concentration Week 388	162 µg/ml Geometric Coefficient of Variation 79.8	—
Period A: Serum Crenezumab Concentration Early Termination Visit	223 µg/ml Geometric Coefficient of Variation 135.5	—
Period A: Serum Crenezumab Concentration Unscheduled	98.4 µg/ml Geometric Coefficient of Variation NA Since only 1 participant was analyzed, the geometric coefficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: Baseline up to approximately Week 416

Population: mITT population included all randomized participants who were mutation carriers and were treated with any amount of study drug.

Amyloid beta is a peptide fragment of the amyloid precursor protein. The annualized rate of change in plasma concentration of Aβ1-40 and Aβ1-42 were estimated using a linear mixed effects model with random intercept and slope.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period A: Annualized Rate of Change in Plasma Concentrations of Amyloid Beta 1(Aβ1)-40 and Amyloid Peptide Beta 42 (Aβ1-42) Aβ1-40	6836.37 (pg/mL)/year Standard Error 236.49	-686.18 (pg/mL)/year Standard Error 234.84
Period A: Annualized Rate of Change in Plasma Concentrations of Amyloid Beta 1(Aβ1)-40 and Amyloid Peptide Beta 42 (Aβ1-42) Aβ1-42	509.44 (pg/mL)/year Standard Error 17.74	-46.59 (pg/mL)/year Standard Error 17.61

SECONDARY outcome

Timeframe: From Day 1 (Period B) up to 67 weeks

Population: Safety population included all randomized participants who received at least 1 dose of study drug in Study Period B; participants are grouped according to the actual treatment received.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. An SAE is any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s); considered a significant medical event by the investigator. During Study Period B, after the results of Study Period A were available, participants had an option to learn their mutation carrier status. Since all participants did not choose to learn their mutation status, pooled data has been presented for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group assigned.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=219 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period B: Number of Participants With AEs and SAEs Participants with AEs	219 Participants	—
Period B: Number of Participants With AEs and SAEs Participants with SAEs	12 Participants	—

SECONDARY outcome

Timeframe: From Day 1 (Period B) up to 67 weeks

Population: Safety population included all randomized participants who received at least 1 dose of study drug in Study Period B; participants are grouped according to the actual treatment received.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. During Study Period B, after the results of Study Period A were available, participants had an option to learn their mutation carrier status. Since all participants did not choose to learn their mutation status, pooled data has been presented for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group assigned.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=219 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period B: Number of Participants Who Withdraw From the Study Treatment Due to AEs	0 Participants	—

SECONDARY outcome

Timeframe: From Day 1 (Period B) up to 67 weeks

Population: Safety population included all randomized participants who received at least 1 dose of study drug in Study Period B; participants are grouped according to the actual treatment received.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. ARIA are a spectrum of image abnormalities detected on MRI. The two types of ARIA reported will include: ARIA-E: refers to the MRI alterations thought to represent VE and related extravasated fluid phenomena, and ARIA-H: refers to the MRI alterations attributable to MBs and leptomeningeal hemosiderosis. Cerebral macrohemorrhages will be read on MRI scans. Occurrence of pneumonia will be verified by imaging (e.g., chest X-ray). During Study Period B, after the results of Study Period A were available, participants had an option to learn their mutation carrier status. Since all participants did not choose to learn their mutation status, pooled data has been presented for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group assigned.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=219 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia Pneumonia	1 Participants	—
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia ARIA-H	0 Participants	—
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia ARIA-E	0 Participants	—
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia Cerebral Macrohemorrhage	0 Participants	—
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia Drug Induced Liver Injury	0 Participants	—
Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia Suspected Transmission of Infectious Agents via a Medicinal Product	0 Participants	—

SECONDARY outcome

Timeframe: From Day 1 (Period B) up to 67 weeks

Population: Safety population included all randomized participants who received at least 1 dose of study drug in Study Period B; participants are grouped according to the actual treatment received.

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Infusion and injection-related reactions are defined as any AEs that occurred during or within 24 hours after the study drug injection or infusion. During Study Period B, after the results of Study Period A were available, participants had an option to learn their mutation carrier status. Since all participants did not choose to learn their mutation status, pooled data has been presented for this outcome measure in order to maintain blinding of the participant's mutation status and treatment group assigned.

Outcome measures

Outcome measures
Measure	Study Period A: Crenezumab - Mutation Carrier n=219 Participants Participants who were PSEN1 E280A mutation carriers, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.
Period B: Number of Participants With Injection Reactions and IRRs Injection Reaction	1 Participants	—
Period B: Number of Participants With Injection Reactions and IRRs Infusion Related Reaction	12 Participants	—

Adverse Events

Study Period A: Crenezumab - Mutation Carriers

Serious events: 23 serious events

Other events: 84 other events

Deaths: 0 deaths

Study Period A: Placebo - Mutation Carriers

Serious events: 21 serious events

Other events: 84 other events

Deaths: 0 deaths

Study Period A: Placebo - Non-Carriers of Mutation

Serious events: 12 serious events

Other events: 83 other events

Deaths: 0 deaths

Study Period A: Combined Blinded

Serious events: 56 serious events

Other events: 251 other events

Deaths: 0 deaths

Study Period B: Crenezumab

Serious events: 9 serious events

Other events: 95 other events

Deaths: 0 deaths

Study Period B: Placebo

Serious events: 3 serious events

Other events: 54 other events

Deaths: 0 deaths

Study Period B: Combined Blinded

Serious events: 12 serious events

Other events: 149 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Study Period A: Crenezumab - Mutation Carriers n=84 participants at risk Participants with PSEN1 E280A mutation, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 participants at risk Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo SC, Q2W, or IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Non-Carriers of Mutation n=83 participants at risk Participants who were non-carriers of PSEN1 E280A mutation, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Study Period A: Combined Blinded n=251 participants at risk All participants who were carriers and non-carriers of PSEN1 E280A mutation and who received either crenezumab placebo 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, or crenezumab matching for a minimum of 260 weeks during Period A are represented in this arm together for the purpose of maintaining blinding for participant's mutation status and treatment group.	Study Period B: Crenezumab n=147 participants at risk Participants who were PSEN1 E280A mutation carriers and who completed treatment with crenezumab or placebo in Period A were given an option to continue receiving crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in Period B for up to 51 weeks.	Study Period B: Placebo n=72 participants at risk Participants who were non-carriers of PSEN1 E280A mutation and who received crenezumab matching placebo in Period A were given an option to continue receiving crenezumab matching placebo SC, Q2W or IV, Q4W in Study Period B, for up to 51 weeks.	Study Period B: Combined Blinded n=219 participants at risk All participants who were carriers and non-carriers of PSEN1 E280A mutation and who received either crenezumab 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, or crenezumab matching placebo for up to 51 weeks during Period B are represented in this arm together for the purpose of maintaining blinding for participant's mutation status and treatment group.
Infections and infestations Infections and infestations	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	4.8% 12/251 • Number of events 13 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	2.3% 5/219 • Number of events 5 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	2.8% 7/251 • Number of events 7 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.91% 2/219 • Number of events 4 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	1.6% 4/251 • Number of events 4 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.91% 2/219 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Nervous system disorders Nervous system disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	1.2% 3/251 • Number of events 3 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	3.2% 8/251 • Number of events 8 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Psychiatric disorders Psychiatric disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	2.0% 5/251 • Number of events 6 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Renal and urinary disorders Renal and urinary disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	2.8% 7/251 • Number of events 7 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Reproductive system and breast disorders Reproductive system and breast disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	1.6% 4/251 • Number of events 4 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Social circumstances Social circumstances	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.40% 1/251 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Cardiac disorders Cardiac disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	1.6% 4/251 • Number of events 4 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Gastrointestinal disorders Gastrointestinal disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	1.2% 3/251 • Number of events 3 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.91% 2/219 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
General disorders General disorders and administration site conditions	27.4% 23/84 • Number of events 30 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	25.0% 21/84 • Number of events 22 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	14.5% 12/83 • Number of events 14 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.80% 2/251 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	6.1% 9/147 • Number of events 18 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	4.2% 3/72 • Number of events 5 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Blood and lymphatic system disorders Blood and lymphatic system disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.40% 1/251 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Congenital, familial and genetic disorders Congenital, familial and genetic disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.40% 1/251 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Endocrine disorders Endocrine disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.40% 1/251 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Hepatobiliary disorders Hepatobiliary disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.40% 1/251 • Number of events 2 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Metabolism and nutrition disorders Metabolism and nutrition disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/251 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/251 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Vascular disorders Vascular disorders	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/84 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/83 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/251 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.46% 1/219 • Number of events 1 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.

Other adverse events

Other adverse events
Measure	Study Period A: Crenezumab - Mutation Carriers n=84 participants at risk Participants with PSEN1 E280A mutation, received crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Mutation Carriers n=84 participants at risk Participants who were PSEN1 E280A mutation carriers, received crenezumab matching placebo SC, Q2W, or IV, Q4W, for a minimum of 260 weeks during Period A.	Study Period A: Placebo - Non-Carriers of Mutation n=83 participants at risk Participants who were non-carriers of PSEN1 E280A mutation, received crenezumab matching placebo, SC, Q2W or IV, Q4W for a minimum of 260 weeks during Period A.	Study Period A: Combined Blinded n=251 participants at risk All participants who were carriers and non-carriers of PSEN1 E280A mutation and who received either crenezumab placebo 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, or crenezumab matching for a minimum of 260 weeks during Period A are represented in this arm together for the purpose of maintaining blinding for participant's mutation status and treatment group.	Study Period B: Crenezumab n=147 participants at risk Participants who were PSEN1 E280A mutation carriers and who completed treatment with crenezumab or placebo in Period A were given an option to continue receiving crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in Period B for up to 51 weeks.	Study Period B: Placebo n=72 participants at risk Participants who were non-carriers of PSEN1 E280A mutation and who received crenezumab matching placebo in Period A were given an option to continue receiving crenezumab matching placebo SC, Q2W or IV, Q4W in Study Period B, for up to 51 weeks.	Study Period B: Combined Blinded n=219 participants at risk All participants who were carriers and non-carriers of PSEN1 E280A mutation and who received either crenezumab 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W, or crenezumab matching placebo for up to 51 weeks during Period B are represented in this arm together for the purpose of maintaining blinding for participant's mutation status and treatment group.
Blood and lymphatic system disorders Blood and lymphatic system disorders	16.7% 14/84 • Number of events 25 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	10.7% 9/84 • Number of events 12 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	9.6% 8/83 • Number of events 13 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	12.4% 31/251 • Number of events 50 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Cardiac disorders Cardiac disorders	9.5% 8/84 • Number of events 12 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.1% 11/84 • Number of events 13 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	7.2% 6/83 • Number of events 8 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	10.0% 25/251 • Number of events 33 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Ear and labyrinth disorders Ear and labyrinth disorders	17.9% 15/84 • Number of events 18 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	11.9% 10/84 • Number of events 21 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	24.1% 20/83 • Number of events 25 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	17.9% 45/251 • Number of events 64 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Endocrine disorders Endocrine disorders	6.0% 5/84 • Number of events 5 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	9.5% 8/84 • Number of events 8 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	6.0% 5/83 • Number of events 5 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	7.2% 18/251 • Number of events 18 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Gastrointestinal disorders Gastrointestinal disorders	65.5% 55/84 • Number of events 141 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	71.4% 60/84 • Number of events 152 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	65.1% 54/83 • Number of events 144 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	66.1% 166/251 • Number of events 437 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.6% 20/147 • Number of events 25 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	15.3% 11/72 • Number of events 11 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	14.2% 31/219 • Number of events 36 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
General disorders General disorders and administration site conditions	46.4% 39/84 • Number of events 82 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	46.4% 39/84 • Number of events 100 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	51.8% 43/83 • Number of events 91 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	48.2% 121/251 • Number of events 273 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Infections and infestations Infections and infestations	100.0% 84/84 • Number of events 772 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	96.4% 81/84 • Number of events 839 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	100.0% 83/83 • Number of events 854 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	98.8% 248/251 • Number of events 2465 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	31.3% 46/147 • Number of events 66 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	40.3% 29/72 • Number of events 44 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	34.2% 75/219 • Number of events 110 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	71.4% 60/84 • Number of events 185 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	69.0% 58/84 • Number of events 190 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	65.1% 54/83 • Number of events 161 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	69.3% 174/251 • Number of events 536 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	15.6% 23/147 • Number of events 33 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.9% 10/72 • Number of events 11 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	25.6% 33/129 • Number of events 44 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Investigations Investigations	20.2% 17/84 • Number of events 21 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	17.9% 15/84 • Number of events 20 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	20.5% 17/83 • Number of events 33 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	19.5% 49/251 • Number of events 74 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Metabolism and nutrition disorders Dyslipidaemia	41.7% 35/84 • Number of events 57 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	26.2% 22/84 • Number of events 31 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	38.6% 32/83 • Number of events 47 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	35.5% 89/251 • Number of events 135 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	5.4% 8/147 • Number of events 9 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	8.3% 6/72 • Number of events 6 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	6.4% 14/219 • Number of events 15 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	76.2% 64/84 • Number of events 177 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	77.4% 65/84 • Number of events 220 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	79.5% 66/83 • Number of events 284 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	77.7% 195/251 • Number of events 681 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	11.6% 17/147 • Number of events 19 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	26.4% 19/72 • Number of events 23 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	16.4% 36/219 • Number of events 42 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Nervous system disorders Nervous system disorders	78.6% 66/84 • Number of events 297 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	83.3% 70/84 • Number of events 311 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	74.7% 62/83 • Number of events 309 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	78.9% 198/251 • Number of events 917 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	18.4% 27/147 • Number of events 45 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	19.4% 14/72 • Number of events 18 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	18.7% 41/219 • Number of events 63 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Psychiatric disorders Psychiatric disorders	51.2% 43/84 • Number of events 109 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	52.4% 44/84 • Number of events 111 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	53.0% 44/83 • Number of events 105 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	52.2% 131/251 • Number of events 325 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	14.3% 21/147 • Number of events 27 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	5.6% 4/72 • Number of events 5 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	11.4% 25/219 • Number of events 32 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Renal and urinary disorders Renal and urinary disorders	21.4% 18/84 • Number of events 28 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	17.9% 15/84 • Number of events 21 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	14.5% 12/83 • Number of events 15 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	17.9% 45/251 • Number of events 64 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Reproductive system and breast disorders Reproductive system and breast disorders	28.6% 24/84 • Number of events 56 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	41.7% 35/84 • Number of events 82 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	47.0% 39/83 • Number of events 100 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	39.0% 98/251 • Number of events 238 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.6% 20/147 • Number of events 23 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.9% 10/72 • Number of events 11 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.7% 30/219 • Number of events 34 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	17.9% 15/84 • Number of events 20 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	20.2% 17/84 • Number of events 23 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	26.5% 22/83 • Number of events 24 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	21.5% 54/251 • Number of events 67 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	45.2% 38/84 • Number of events 91 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	48.8% 41/84 • Number of events 75 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	57.8% 48/83 • Number of events 93 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	50.6% 127/251 • Number of events 259 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	5.4% 8/147 • Number of events 10 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	9.7% 7/72 • Number of events 7 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	6.8% 15/219 • Number of events 17 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Vascular disorders Vascular disorders	17.9% 15/84 • Number of events 17 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	23.8% 20/84 • Number of events 26 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	21.7% 18/83 • Number of events 23 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	21.1% 53/251 • Number of events 66 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Eye disorders Eye disorders	23.8% 20/84 • Number of events 25 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	11.9% 10/84 • Number of events 17 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	16.9% 14/83 • Number of events 17 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	17.5% 44/251 • Number of events 59 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	6.0% 5/84 • Number of events 6 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	13.1% 11/84 • Number of events 11 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	14.5% 12/83 • Number of events 13 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	11.2% 28/251 • Number of events 30 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/147 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/72 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.	0.00% 0/219 • Period A: Baseline up to approximately 416 weeks; Period B: Day 1 (Period B) up to 67 weeks. To protect the mutation status in Periods A & B, for deaths & SAEs: data are reported in each arm under system organ class (SOC) of General Disorders & participant level data are reported in Combined Blinded arms only. All arms were considered to be at Risk for all deaths/SAEs although participant level data are reported in Combined blinded arms only. Data for OAEs are reported under SOC's for all arms. Safety population used for Period A\&B. Period A= 1 participant excluded from safety population for not meeting 1 of the eligibility criteria prior to treatment start. During Period B, after Period A results were available, participants had an option to learn their mutation status. All participants did not choose to learn their mutation status. Hence, pooled data has been presented to maintain blinding of participant's mutation status \& treatment assignment. OAEs=Other Adverse Events.

Additional Information

Medical Communications

Hoffmann-La Roche

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
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Restriction type: OTHER