Trial Outcomes & Findings for Tau Positron Emission Tomography (PET) Longitudinal Substudy Associated With: Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers in the Treatment of Autosomal-Dominant Alzheimer's Disease (NCT NCT03977584)

Last Updated: 2024-03-15

Results Overview

Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using \[18F\]GTP1 Tau PET. The annualized rate of change in tau burden from the first \[18F\]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Baseline up to Week 149

Results posted on

2024-03-15

Participant Flow

This sub-study enrolled participants from the main study: NCT01998841, who consented to participate in it. Participants took part in this sub-study from 10 Jun 2019 to 19 Apr 2022.

114 participants enrolled in this sub-study.

Participant milestones

Participant milestones
Measure	Crenezumab - Mutation Carriers Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 milligrams (mg), subcutaneously (SC), every two weeks (Q2W), or 60 milligrams per kilograms (mg/kg), intravenously (IV), every four weeks (Q4W) in the main study (NCT01998841) received up to three intravenous (IV) injections of \[\^18F\] Genentech Tau Probe 1 (GTP1) and underwent a tau positron emission tomography (PET) scan after each IV injection of \[\^18F\]GTP1.	Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Placebo - Non-Carriers of Mutation Participants who were non-carriers of PSEN1 E280A mutation and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.
Overall Study STARTED	44	39	31
Overall Study COMPLETED	42	39	27
Overall Study NOT COMPLETED	2	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Crenezumab - Mutation Carriers Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 milligrams (mg), subcutaneously (SC), every two weeks (Q2W), or 60 milligrams per kilograms (mg/kg), intravenously (IV), every four weeks (Q4W) in the main study (NCT01998841) received up to three intravenous (IV) injections of \[\^18F\] Genentech Tau Probe 1 (GTP1) and underwent a tau positron emission tomography (PET) scan after each IV injection of \[\^18F\]GTP1.	Placebo - Mutation Carriers Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Placebo - Non-Carriers of Mutation Participants who were non-carriers of PSEN1 E280A mutation and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.
Overall Study Reason not disclosed to prevent genetic unblinding	2	0	4

Baseline Characteristics

Tau Positron Emission Tomography (PET) Longitudinal Substudy Associated With: Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers in the Treatment of Autosomal-Dominant Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crenezumab - Mutation Carriers n=44 Participants Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Placebo - Mutation Carriers n=39 Participants Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Placebo - Non-Carriers of Mutation n=31 Participants Participants who were non-carriers of PSEN1 E280A mutation and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Total n=114 Participants Total of all reporting groups
Age, Continuous	36.0 years STANDARD_DEVIATION 5.5 • n=5 Participants	36.7 years STANDARD_DEVIATION 7.3 • n=7 Participants	41.8 years STANDARD_DEVIATION 8.0 • n=5 Participants	37.8 years STANDARD_DEVIATION 7.2 • n=4 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	29 Participants n=7 Participants	23 Participants n=5 Participants	73 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	41 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	44 Participants n=5 Participants	39 Participants n=7 Participants	31 Participants n=5 Participants	114 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 Race · American Indian or Alaska Native	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	17 Participants n=5 Participants	22 Participants n=7 Participants	14 Participants n=5 Participants	53 Participants n=4 Participants
Race/Ethnicity, Customized Race · Multiple	15 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	35 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	4 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Race · Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 149

Population: Modified Intent-to-Treat (mITT) population included all mutation carrier participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Crenezumab - Mutation Carriers n=44 Participants Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three intravenous (IV) injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Placebo - Mutation Carriers n=39 Participants Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.
Annualized Rate of Change in Tau Burden	0.0124 SUVR per year Standard Error 0.00752	0.0254 SUVR per year Standard Error 0.00768

Adverse Events

Combined Blinded

Serious events: 9 serious events

Other events: 110 other events

Deaths: 0 deaths

Crenezumab - Mutation Carriers

Serious events: 4 serious events

Other events: 43 other events

Deaths: 0 deaths

Pooled Placebo

Serious events: 5 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Combined Blinded n=114 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 matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Crenezumab - Mutation Carriers n=44 participants at risk Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\] GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Pooled Placebo n=70 participants at risk Carriers and non-carriers of PSEN1 E280A mutation who received matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841), received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	1.8% 2/114 • Number of events 2 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Gastrointestinal disorders Gastrointestinal disorders	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
General disorders General disorders and administration site conditions	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	9.1% 4/44 • Number of events 5 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	7.1% 5/70 • Number of events 5 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Infections and infestations Infections and infestations	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Psychiatric disorders Psychiatric disorders	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Renal and urinary disorders Renal and urinary disorders	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Reproductive system and breast disorders Reproductive system and breast disorders	0.88% 1/114 • Number of events 1 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/44 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	0.00% 0/39 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.

Other adverse events

Other adverse events
Measure	Combined Blinded n=114 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 matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Crenezumab - Mutation Carriers n=44 participants at risk Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three IV injections of \[\^18F\] GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.	Pooled Placebo n=70 participants at risk Carriers and non-carriers of PSEN1 E280A mutation who received matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841), received up to three IV injections of \[\^18F\]GTP1 and underwent a tau PET scan after each IV injection of \[\^18F\]GTP1.
Infections and infestations Infections and infestations	78.9% 90/114 • Number of events 201 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	81.8% 36/44 • Number of events 67 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	77.1% 54/70 • Number of events 134 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	45.6% 52/114 • Number of events 128 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	50.0% 22/44 • Number of events 58 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	42.9% 30/70 • Number of events 70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	42.1% 48/114 • Number of events 70 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	45.5% 20/44 • Number of events 30 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	40.0% 28/70 • Number of events 40 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Nervous system disorders Nervous system disorders	36.8% 42/114 • Number of events 78 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	36.4% 16/44 • Number of events 32 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	37.1% 26/70 • Number of events 46 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Psychiatric disorders Psychiatric disorders	28.1% 32/114 • Number of events 46 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	22.7% 10/44 • Number of events 17 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	31.4% 22/70 • Number of events 29 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Gastrointestinal disorders Gastrointestinal disorders	26.3% 30/114 • Number of events 42 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	34.1% 15/44 • Number of events 22 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	21.4% 15/70 • Number of events 20 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
General disorders General disorders and administration site conditions	17.5% 20/114 • Number of events 25 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	13.6% 6/44 • Number of events 9 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	20.0% 14/70 • Number of events 16 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Reproductive system and breast disorders Reproductive system and breast disorders	15.8% 18/114 • Number of events 22 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	9.1% 4/44 • Number of events 5 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	20.0% 14/70 • Number of events 17 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Metabolism and nutrition disorders Metabolism and nutrition disorders	12.3% 14/114 • Number of events 16 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	13.6% 6/44 • Number of events 6 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	11.4% 8/70 • Number of events 10 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	12.3% 14/114 • Number of events 16 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	13.6% 6/44 • Number of events 8 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	11.4% 8/70 • Number of events 8 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Renal and urinary disorders Renal and urinary disorders	11.4% 13/114 • Number of events 14 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	13.6% 6/44 • Number of events 6 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	10.0% 7/70 • Number of events 8 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	11.4% 13/114 • Number of events 14 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	11.4% 5/44 • Number of events 6 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.	11.4% 8/70 • Number of events 8 • Up to Week 149 Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.

Additional Information

BN40199

Hoffmann-La Roche

Phone: 888-662-6728 (U.S. Only)

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.
Publication restrictions are in place

Restriction type: OTHER