Trial Outcomes & Findings for A Study of Gantenerumab in Participants With Mild Alzheimer Disease (NCT NCT02051608)

NCT ID: NCT02051608

Last Updated: 2023-02-10

Results Overview

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

389 participants

Primary outcome timeframe

First dose up to 4 weeks after the last dose of study drug (up to 249 weeks)

Results posted on

2023-02-10

Participant Flow

Part 1 of the study was conducted at 116 centers in 21 countries and part 2 was conducted at 75 centers in 17 countries.

A total of 389 participants were enrolled out of which 387 were randomized and treated (192 received gantenerumab and 195 received placebo) in part 1 of the study. Of these, a total of 230 participants enrolled into Part 2 of the study: 225 participants received at least one dose of study drug. Participants who had discontinued from Part 1 of the study were not allowed to enroll in Part 2.

Participant milestones

Participant milestones
Measure	Part 1: Placebo Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of study.	Part 1: Gantenerumab Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Double Blind Treatment STARTED	195	192	0	0
Part 1: Double Blind Treatment COMPLETED	134	136	0	0
Part 1: Double Blind Treatment NOT COMPLETED	61	56	0	0
Part 2: Open-label Extension STARTED	0	0	119	111
Part 2: Open-label Extension COMPLETED	0	0	49	50
Part 2: Open-label Extension NOT COMPLETED	0	0	70	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Placebo Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of study.	Part 1: Gantenerumab Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Double Blind Treatment Death	3	3	0	0
Part 1: Double Blind Treatment Adverse Event	2	8	0	0
Part 1: Double Blind Treatment Withdrawal by Subject	42	29	0	0
Part 1: Double Blind Treatment Physician Decision	2	4	0	0
Part 1: Double Blind Treatment Lost to Follow-up	1	2	0	0
Part 1: Double Blind Treatment Protocol Violation	0	1	0	0
Part 1: Double Blind Treatment Non-Compliance	2	4	0	0
Part 1: Double Blind Treatment Other	6	3	0	0
Part 1: Double Blind Treatment Part 1 Terminated by Sponsor	3	2	0	0
Part 2: Open-label Extension Adverse Event	0	0	6	8
Part 2: Open-label Extension Death	0	0	7	4
Part 2: Open-label Extension Lost to Follow-up	0	0	0	1
Part 2: Open-label Extension Non-Compliance	0	0	1	1
Part 2: Open-label Extension Withdrawal by Subject	0	0	39	32
Part 2: Open-label Extension Study Terminated By Sponsor	0	0	0	1
Part 2: Open-label Extension Physician Decision	0	0	8	5
Part 2: Open-label Extension Other	0	0	9	9

Baseline Characteristics

Part 2 of the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Placebo n=195 Participants Participants received matching placebo by SC injection every 4 weeks Q4W up to 100 weeks during Part 1 of study.	Part 1: Gantenerumab n=192 Participants Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=117 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=108 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Total n=612 Participants Total of all reporting groups
Race (NIH/OMB) Asian	23 Participants n=195 Participants • Part 1 of the study.	21 Participants n=192 Participants • Part 1 of the study.	19 Participants n=117 Participants • Part 2 of the study.	19 Participants n=108 Participants • Part 2 of the study.	44 Participants n=387 Participants • Part 1 of the study.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=195 Participants • Part 1 of the study.	1 Participants n=192 Participants • Part 1 of the study.	0 Participants n=117 Participants • Part 2 of the study.	1 Participants n=108 Participants • Part 2 of the study.	1 Participants n=225 Participants • Part 2 of the study.
Age, Continuous	70.1 years STANDARD_DEVIATION 8.6 • n=195 Participants • Part 1 of the study.	69.7 years STANDARD_DEVIATION 8.9 • n=192 Participants • Part 1 of the study.	71.82 years STANDARD_DEVIATION 8.09 • n=117 Participants • Part 2 of the study.	71.01 years STANDARD_DEVIATION 9.31 • n=108 Participants • Part 2 of the study.	71.43 years STANDARD_DEVIATION 8.69 • n=225 Participants • Part 2 of the study.
Sex: Female, Male Female	113 Participants n=195 Participants • Part 1 of the study.	98 Participants n=192 Participants • Part 1 of the study.	69 Participants n=117 Participants • Part 2 of the study.	61 Participants n=108 Participants • Part 2 of the study.	130 Participants n=225 Participants • Part 2 of the study.
Sex: Female, Male Male	82 Participants n=195 Participants • Part 1 of the study.	94 Participants n=192 Participants • Part 1 of the study.	48 Participants n=117 Participants • Part 2 of the study.	47 Participants n=108 Participants • Part 2 of the study.	95 Participants n=225 Participants • Part 2 of the study.
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=195 Participants • Part 1 of the study.	12 Participants n=192 Participants • Part 1 of the study.	9 Participants n=117 Participants • Part 2 of the study.	10 Participants n=108 Participants • Part 2 of the study.	19 Participants n=225 Participants • Part 2 of the study.
Ethnicity (NIH/OMB) Not Hispanic or Latino	178 Participants n=195 Participants • Part 1 of the study.	176 Participants n=192 Participants • Part 1 of the study.	108 Participants n=117 Participants • Part 2 of the study.	96 Participants n=108 Participants • Part 2 of the study.	204 Participants n=225 Participants • Part 2 of the study.
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=195 Participants • Part 1 of the study.	4 Participants n=192 Participants • Part 1 of the study.	0 Participants n=117 Participants • Part 2 of the study.	2 Participants n=108 Participants • Part 2 of the study.	2 Participants n=225 Participants • Part 2 of the study.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=195 Participants • Part 1 of the study.	0 Participants n=192 Participants • Part 1 of the study.	0 Participants n=117 Participants • Part 2 of the study.	0 Participants n=108 Participants • Part 2 of the study.	0 Participants n=225 Participants • Part 2 of the study.
Race (NIH/OMB) Black or African American	2 Participants n=195 Participants • Part 1 of the study.	2 Participants n=192 Participants • Part 1 of the study.	2 Participants n=117 Participants • Part 2 of the study.	2 Participants n=108 Participants • Part 2 of the study.	4 Participants n=225 Participants • Part 2 of the study.
Race (NIH/OMB) White	164 Participants n=195 Participants • Part 1 of the study.	166 Participants n=192 Participants • Part 1 of the study.	94 Participants n=117 Participants • Part 2 of the study.	85 Participants n=108 Participants • Part 2 of the study.	179 Participants n=225 Participants • Part 2 of the study.
Race (NIH/OMB) More than one race	1 Participants n=195 Participants • Part 1 of the study.	0 Participants n=192 Participants • Part 1 of the study.	0 Participants n=117 Participants • Part 2 of the study.	0 Participants n=108 Participants • Part 2 of the study.	0 Participants n=225 Participants • Part 2 of the study.
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=195 Participants • Part 1 of the study.	2 Participants n=192 Participants • Part 1 of the study.	2 Participants n=117 Participants • Part 2 of the study.	1 Participants n=108 Participants • Part 2 of the study.	3 Participants n=225 Participants • Part 2 of the study.

PRIMARY outcome

Timeframe: First dose up to 4 weeks after the last dose of study drug (up to 249 weeks)

Population: The safety-evaluable population consisted of all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=117 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=108 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) SAEs	24.8 Percentage of Participants	38.0 Percentage of Participants
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) AEs	91.5 Percentage of Participants	95.4 Percentage of Participants

PRIMARY outcome

Timeframe: First dose up to last dose (Baseline up to until maximum 5 years)

Population: The safety population consisted of all participants who had received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not. The number of participants analyzed indicates the number of participants evaluated for the outcome measure.

Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for participants previously (in part 1) on Gantenerumab and Placebo. The prevalence of ADA at baseline was calculated as the percentage of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the percentage of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=115 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=106 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)	2.6 Percentage of Participants	2.8 Percentage of Participants

PRIMARY outcome

Timeframe: First dose up to 4 weeks after the last dose in OLE (Up to approximately 249 weeks)

Population: The safety population consisted of all participants who had received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not.

Percentage of participants with adverse events leading to discontinuation from treatment were reported.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=117 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=108 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment	12.0 Percentage of Participants	15.7 Percentage of Participants

SECONDARY outcome

Timeframe: First dose up to last dose (Up to approximately 152 weeks)

Population: The safety population consisted of all participants who received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A serious adverse event is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=195 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=192 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Percentage of Participants With AEs, SAEs SAEs	12.3 Percentage of Participants	12.0 Percentage of Participants
Part 1: Percentage of Participants With AEs, SAEs AEs	80.5 Percentage of Participants	82.8 Percentage of Participants

SECONDARY outcome

Timeframe: First dose up to last dose (Up to approximately 152 weeks)

Population: The safety population consisted of all participants who received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not. The number of participants analyzed indicates the number of participants evaluated for the outcome measure.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=194 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=191 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Percentage of Participants With Treatment Emergent ADAs	3.6 Percentage of Participants	11.5 Percentage of Participants

SECONDARY outcome

Timeframe: Pre-dose: Weeks 4, 8, 12, 24, 48, 72 and Post dose: Day 4

Population: The pharmacokinetic (PK) evaluable population consisted of all participants that were treated with gantenerumab and provided at least 1 post-baseline PK sample. Number analyzed is the number of participants with data available for analyses at the given time-point.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=192 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Day 4	4.11 μg/mL Standard Deviation 2.59	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 4	2.06 μg/mL Standard Deviation 0.89	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 8	3.11 μg/mL Standard Deviation 1.41	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 12	3.35 μg/mL Standard Deviation 1.63	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 24	3.71 μg/mL Standard Deviation 2.13	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 48	7.61 μg/mL Standard Deviation 3.88	—
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints Week 72	7.66 μg/mL Standard Deviation 4.44	—

SECONDARY outcome

Timeframe: First dose up to last dose (Up to approximately 152 weeks)

Population: The safety population consisted of all participants who received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not.

Percentage of participants with adverse events leading to discontinuation from treatment were reported.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=195 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=192 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 1: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment	2.6 Percentage of Participants	6.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Part 1 screening), Week 104

Population: The safety population consisted of all participants who received at least one dose of gantenerumab during the OLE and also had at least one post baseline MRI. The number of participants analyzed indicates the number of participants evaluated for the outcome measure. Number analyzed is the number of participants with data available for analyses at the given time-point.

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analyzed at Week 104 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=52 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=44 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104 Hippocampal Left Volume- Percent Change at Week 104	-11.24 Percent Change Standard Deviation 4.04	-12.10 Percent Change Standard Deviation 4.45
Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104 Hippocampal Right Volume- Percent Change at Week 104	-12.49 Percent Change Standard Deviation 4.03	-11.34 Percent Change Standard Deviation 4.41

SECONDARY outcome

Timeframe: Baseline (Part 1 screening), Week 104

Change from baseline brain volume were analyzed at Week 104 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=54 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=44 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104	-4.89 Percent Change Standard Deviation 1.90	-4.91 Percent Change Standard Deviation 1.58

SECONDARY outcome

Timeframe: Baseline (Part 1 screening), Week 104

Change from baseline in cortical thickness were analyzed at Week 104 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=54 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=44 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Percent Change From Baseline in Cortical Thickness at Week 104	-5.84 Percent Change Standard Deviation 2.33	-5.58 Percent Change Standard Deviation 1.87

SECONDARY outcome

Timeframe: Part 2: Week 104

Ventricular volume were analyzed at Week 104 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=63 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=52 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Ventricular Volume as Measured by MRI at Week 104	86.70 mL Standard Deviation 38.37	86.21 mL Standard Deviation 30.49

SECONDARY outcome

Timeframe: Pre-dose: Weeks 104, 116, 156, 208; Post-dose: Weeks 53, 101

Population: Of the 225 participants in the OLE safety evaluable population, evaluable PK information was available from 223 participants. The PK evaluable population consisted of all participants that were treated with gantenerumab and provided at least 1 post-baseline PK sample. Number analysed is the number of participants with data available for analyses at the given time-point.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=223 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 53	80.6 μg/mL Standard Deviation 38.4	—
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 101	89.1 μg/mL Standard Deviation 33.6	—
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 104	43.5 μg/mL Standard Deviation 22.4	—
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 116	3.66 μg/mL Standard Deviation 2.29	—
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 156	45.2 μg/mL Standard Deviation 22.5	—
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints Week 208	55.8 μg/mL Standard Deviation 37.9	—

SECONDARY outcome

Timeframe: Baseline, Week 156

Population: The safety population consisted of all participants who had received at least one dose of study drug, regardless of whether the participants withdrew prematurely or not. The number of participants analysed indicates the number of participants evaluated for the outcome measure.

Brain amyloid load over time was assessed using a Florbetapir \[F18\] injection, a positron emission tomography (PET) radioligand selective to amyloid. Analysis was conducted in a subset of participants who signed consent to participate in the PET substudy. Amyloid PET burden was measured in a composite region of interest (ROI) by using standardized uptake value ratio (SUVR) mapped to the centiloid scale. The composite region was composed of the following six bilateral regions: frontal lobe, parietal lobe, temporal lobe, posterior cingulate cortex, anterior cingulate cortex. The reference region used to normalize the composite region was the cerebellar cortex. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans.

Outcome measures

Outcome measures
Measure	Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg n=13 Participants Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.	Part 2 (OLE Treatment): Gantenerumab up to 1200 mg n=8 Participants Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants	-81.01 Score on a scale Standard Deviation 47.08	-84.93 Score on a scale Standard Deviation 28.38

Serious events: 53 serious events

Other events: 147 other events

Deaths: 11 deaths

Part 1: Gantenerumab

Serious events: 61 serious events

Other events: 159 other events

Deaths: 8 deaths

Part 2 (OLE Treatment): Placebo Switched to Gantenerumab up to 1200 mg

Serious events: 29 serious events

Other events: 94 other events

Deaths: 5 deaths

Part 2 (OLE Treatment): Gantenerumab up to 1200 mg

Serious events: 41 serious events

Other events: 91 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

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