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Clinical Trial Results:
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients

Summary
EudraCT number	2013-003390-95
Trial protocol	GB DE SE ES PT IT NL BE HU FI BG DK FR
Global end of trial date	16 Apr 2021

Results information
Results version number	v2(current)
This version publication date	22 Jul 2022
First version publication date	25 Apr 2022
Other versions	v1
Version creation reason	Correction of full data set Updated pre-assignment details, updated overall number of participants analysed, timeframe, and unit of measure in the endpoint.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

WN28745

ISRCTN number

US NCT number

NCT02051608

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 Apr 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Apr 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the effect of subcutaneous Gantenerumab on cognition and function in mild Alzheimer’s disease.

Protection of trial subjects

All study subjects were required to sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Mar 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 9

Country: Number of subjects enrolled

Argentina: 7

Country: Number of subjects enrolled

Belgium: 4

Country: Number of subjects enrolled

Canada: 34

Country: Number of subjects enrolled

Switzerland: 4

Country: Number of subjects enrolled

Germany: 16

Country: Number of subjects enrolled

Denmark: 14

Country: Number of subjects enrolled

Spain: 31

Country: Number of subjects enrolled

Finland: 4

Country: Number of subjects enrolled

France: 15

Country: Number of subjects enrolled

United Kingdom: 18

Country: Number of subjects enrolled

Hungary: 5

Country: Number of subjects enrolled

Italy: 19

Country: Number of subjects enrolled

Japan: 21

Country: Number of subjects enrolled

Korea, Republic of: 22

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

Portugal: 6

Country: Number of subjects enrolled

Russian Federation: 28

Country: Number of subjects enrolled

Sweden: 14

Country: Number of subjects enrolled

Turkey: 13

Country: Number of subjects enrolled

United States: 95

Worldwide total number of subjects

387

EEA total number of subjects

136

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

105

From 65 to 84 years

273

85 years and over

Subject disposition

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Recruitment details

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

Screening details

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

Period 1 title

Part 1: Double Blind Treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Part 1: Placebo

Arm description

Participants received matching placebo by SC injection Q4W up to 100 weeks during Part 1 of the study.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received gantenerumab matching placebo SC injection Q4W.

Part 1: Gantenerumab

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Gantenerumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received gantenerumab SC injection Q4W.

Number of subjects in period 1	Part 1: Placebo	Part 1: Gantenerumab
Started	195	192
Completed	134	136
Not completed	61	56
Physician decision	2	4
Non-Compliance	2	4
Part 1 Terminated by Sponsor	3	2
Death	3	3
Not specified	6	3
Adverse event	2	8
Lost to follow-up	1	2
Withdrawal by subject	42	29
Protocol deviation	-	1

Period 2 title

Part 2: Open-label Extension

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Gantenerumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received gantenerumab SC injection Q4W

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

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Gantenerumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received gantenerumab SC injection Q4W

Number of subjects in period 2 ^[1]	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Started	119	111
Completed	49	50
Not completed	70	61
Physician decision	8	5
Non-Compliance	1	1
Study Terminated By Sponsor	-	1
Death	7	4
Not specified	9	9
Adverse event	6	8
Withdrawal by subjects	39	32
Lost to follow-up	-	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: A total of 230 participants were enrolled in OLE. Of these, 225 were treated in OLE phase.

Baseline characteristics

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Reporting group title

Part 1: Placebo

Reporting group description

Participants received matching placebo by SC injection Q4W up to 100 weeks during Part 1 of the study.

Reporting group title

Part 1: Gantenerumab

Reporting group description

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.

Reporting group values	Part 1: Placebo	Part 1: Gantenerumab	Total
Number of subjects	195	192	387
Age categorical
Units: Participants
Age Continuous
Units: years
arithmetic mean (standard deviation)	70.1 ( 8.6 )	69.7 ( 8.9 )	-
Sex: Female, Male
Units: Participants
Female	113	98	211
Male	82	94	176
Ethnicity
Units: Subjects
Hispanic or Latino	11	12	23
Not Hispanic or Latino	178	176	354
Unknown or Not Reported	6	4	10
Race
Units: Subjects
Asian	23	21	44
Black or African American	2	2	4
Native Hawaiian or other Pacific Islander	0	1	1
White	164	166	330
More than one race	1	0	1
Unknown or Not Reported	5	2	7
American Indian or Alaska Native	0	0	0

Subject analysis set title

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

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Part 2 (OLE): Gantenerumab up to 1200 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Part 2 (OLE): Gantenerumab 1200 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who had received placebo or gantenerumab 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.

Subject analysis sets values	Part 2 (OLE): Placebo switched to Gantenerumab up to 1200 mg	Part 2 (OLE): Gantenerumab up to 1200 mg	Part 2 (OLE): Gantenerumab 1200 mg
Number of subjects	117	108	223
Age categorical
Units: Participants
Age Continuous
Units: years
arithmetic mean (standard deviation)	71.82 ( 8.09 )	71.01 ( 9.31 )	( )
Sex: Female, Male
Units: Participants
Female	69	61
Male	48	47
Ethnicity
Units: Subjects
Hispanic or Latino	9	10
Not Hispanic or Latino	108	96
Unknown or Not Reported	0	2
Race
Units: Subjects
Asian	19	19
Black or African American	2	2
Native Hawaiian or other Pacific Islander	0	1
White	94	85
More than one race	0	0
Unknown or Not Reported	2	1
American Indian or Alaska Native	0	0

End points

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Reporting group title

Part 1: Placebo

Reporting group description

Participants received matching placebo by SC injection Q4W up to 100 weeks during Part 1 of the study.

Reporting group title

Part 1: Gantenerumab

Reporting group description

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.

Reporting group title

Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg

Reporting group description

Reporting group title

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

Reporting group description

Subject analysis set title

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

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Part 2 (OLE): Gantenerumab up to 1200 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Part 2 (OLE): Gantenerumab 1200 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs)

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End point title

Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs) ^[1]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	117	108
Units: Percentage of Participants
number (not applicable)
AEs	91.5	95.4
SAEs	24.8	38.0

No statistical analyses for this end point

Primary: Part 2: Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs)

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End point title

Part 2: Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs) ^[2]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	115 ^[3]	106 ^[4]
Units: Percentage of Participants
number (not applicable)	2.6	2.8

Notes
[3] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[4] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Primary: Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment

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End point title

Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment ^[5]

End point description

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

End point type

Primary

End point timeframe

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

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	117	108
Units: Percentage of Participants
number (not applicable)	12.0	15.7

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants With AEs, SAEs

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End point title

Part 1: Percentage of Participants With AEs, SAEs

End point description

End point type

Secondary

End point timeframe

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

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	195	192
Units: Percentage of Participants
number (not applicable)
AEs	80.5	82.8
SAEs	12.3	12.0

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Treatment-emergent ADAs

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End point title

Part 1: Percentage of Participants with Treatment-emergent ADAs

End point description

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 Gantenerumab and Placebo groups. 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.

End point type

Secondary

End point timeframe

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

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	194 ^[6]	191 ^[7]
Units: Percentage of Participants
number (not applicable)	3.6	11.5

Notes
[6] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[7] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints

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End point title

Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints ^[8]

End point description

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

End point type

Secondary

End point timeframe

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

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses were performed

End point values	Part 1: Gantenerumab
Number of subjects analysed	192
Units: μg/mL
arithmetic mean (standard deviation)
Day 4 (n=183)	4.11 ( 2.59 )
Week 4 (n=190)	2.06 ( 0.89 )
Week 8 (n=188)	3.11 ( 1.41 )
Week 12 (n=184)	3.35 ( 1.63 )
Week 24 (n=177)	3.71 ( 2.13 )
Week 48 (n=137)	7.61 ( 3.88 )
Week 72 (n=79)	7.66 ( 4.44 )

No statistical analyses for this end point

Secondary: Part 1: Percentage of Participants with Adverse Events Leading to Discontinuation of Treatment

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End point title

Part 1: Percentage of Participants with Adverse Events Leading to Discontinuation of Treatment

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	195	192
Units: Percentage of Participants
number (not applicable)	2.6	6.8

No statistical analyses for this end point

Secondary: Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104

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End point title

Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104

End point description

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging. 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. Number analyzed is the number of participants with data available for analyses at the given time-point.

End point type

Secondary

End point timeframe

Baseline (Part 1 screening), Week 104

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	52 ^[9]	44 ^[10]
Units: Percent Change
arithmetic mean (standard deviation)
HLV- Percent Change at Week 104 (n=50, n=43)	-11.24 ( 4.04 )	-12.10 ( 4.45 )
HRV- Percent Change at Week 104 (n=52, n=44)	-12.49 ( 4.03 )	-11.34 ( 4.41 )

Notes
[9] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[10] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104

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End point title

Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104

End point description

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

End point type

Secondary

End point timeframe

Baseline (Part 1 screening), Week 104

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	54 ^[11]	44 ^[12]
Units: Percent Change
arithmetic mean (standard deviation)	-4.89 ( 1.90 )	-4.91 ( 1.58 )

Notes
[11] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[12] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 2: Percent Change From Baseline in Cortical Thickness at Week 104

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End point title

Part 2: Percent Change From Baseline in Cortical Thickness at Week 104

End point description

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

End point type

Secondary

End point timeframe

Baseline (Part 1 screening), Week 104

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	54 ^[13]	44 ^[14]
Units: Percent Change
arithmetic mean (standard deviation)	-5.84 ( 2.33 )	-5.58 ( 1.87 )

Notes
[13] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[14] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 2: Ventricular Volume as Measured by MRI at Week 104

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End point title

Part 2: Ventricular Volume as Measured by MRI at Week 104

End point description

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

End point type

Secondary

End point timeframe

Part 2: Week 104

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	63 ^[15]	52 ^[16]
Units: mL
arithmetic mean (standard deviation)	86.70 ( 38.37 )	86.21 ( 30.49 )

Notes
[15] - The number of participants analysed indicates the number of participants evaluated for the endpoint.
[16] - The number of participants analysed indicates the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints

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End point title

Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints

End point description

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. “n” = number analysed is the number of participants with data available for analyses at the given time-point.

End point type

Secondary

End point timeframe

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

End point values	Part 2 (OLE): Gantenerumab 1200 mg
Number of subjects analysed	223 ^[17]
Units: μg/mL
arithmetic mean (standard deviation)
Week 53 (n=128)	80.6 ( 38.4 )
Week 101 (n=111)	89.1 ( 33.6 )
Week 104 (n=141)	43.5 ( 22.4 )
Week 116 (n=15)	3.66 ( 2.29 )
Week 156 (n=80)	45.2 ( 22.5 )
Week 208 (n=48)	55.8 ( 37.9 )

Notes
[17] - The number of participants analysed indicated the number of participants evaluated for the endpoint.

No statistical analyses for this end point

Secondary: Part 2: Change from Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants

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End point title

Part 2: Change from Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants

End point description

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. Safety population.

End point type

Secondary

End point timeframe

Baseline, Week 156

End point values	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Number of subjects analysed	13 ^[18]	8 ^[19]
Units: Score on a scale
arithmetic mean (standard deviation)	-81.01 ( 47.08 )	-84.93 ( 28.38 )

Notes
[18] - Participants who had discontinued from Part 1 of the study were not allowed to enroll in Part 2.
[19] - Participants who had discontinued from Part 1 of the study were not allowed to enroll in Part 2.

No statistical analyses for this end point

Other pre-specified: Part 1: Mean Change from Baseline in Alzheimer's Disease Activity Scale-Cognitive Subscale 13 (ADAS-Cog13) Scores at Week 104

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End point title

Part 1: Mean Change from Baseline in Alzheimer's Disease Activity Scale-Cognitive Subscale 13 (ADAS-Cog13) Scores at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[20]	0 ^[21]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[20] - For part 1, the efficacy endpoints became exploratory in nature.
[21] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104

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End point title

Part 1: Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[22]	0 ^[23]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[22] - For part 1, the efficacy endpoints became exploratory in nature.
[23] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percentage Change From Baseline in Total Tau (t-tau) in CSF at Week 104

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End point title

Part 1: Percentage Change From Baseline in Total Tau (t-tau) in CSF at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[24]	0 ^[25]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[24] - For part 1, the efficacy endpoints became exploratory in nature.
[25] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percentage Change From Baseline in Abeta 1-42 levels in CSF at Week 104

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End point title

Part 1: Percentage Change From Baseline in Abeta 1-42 levels in CSF at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[26]	0 ^[27]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[26] - For part 1, the efficacy endpoints became exploratory in nature.
[27] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percentage Change From Baseline in phosphorylated tau [p-tau] in CSF at Week 104

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End point title

Part 1: Percentage Change From Baseline in phosphorylated tau [p-tau] in CSF at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[28]	0 ^[29]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[28] - For part 1, the efficacy endpoints became exploratory in nature.
[29] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percent Change From Baseline in Hippocampal Volume at Week 104

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End point title

Part 1: Percent Change From Baseline in Hippocampal Volume at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[30]	0 ^[31]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[30] - For part 1, the efficacy endpoints became exploratory in nature.
[31] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percent Change From Baseline in Whole Brain Volume at Week 104

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End point title

Part 1: Percent Change From Baseline in Whole Brain Volume at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[32]	0 ^[33]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[32] - For part 1, the efficacy endpoints became exploratory in nature.
[33] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percent Change From Baseline in Cortical Thickness at Week 104

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End point title

Part 1: Percent Change From Baseline in Cortical Thickness at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[34]	0 ^[35]
Units: Percent Change
arithmetic mean (standard deviation)	( )	( )

Notes
[34] - For part 1, the efficacy endpoints became exploratory in nature.
[35] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Ventricular Volume as Measured by MRI at Week 104

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End point title

Part 1: Ventricular Volume as Measured by MRI at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[36]	0 ^[37]
Units: ml
arithmetic mean (standard deviation)	( )	( )

Notes
[36] - For part 1, the efficacy endpoints became exploratory in nature.
[37] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104

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End point title

Part 1: Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[38]	0 ^[39]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[38] - For part 1, the efficacy endpoints became exploratory in nature.
[39] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in CDR Sum of Boxes (SB) at Week 104

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End point title

Part 1: Change From Baseline in CDR Sum of Boxes (SB) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[40]	0 ^[41]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[40] - For part 1, the efficacy endpoints became exploratory in nature.
[41] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104

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End point title

Part 1: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[42]	0 ^[43]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[42] - For part 1, the efficacy endpoints became exploratory in nature.
[43] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in NPI Domain Score at Week 104

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End point title

Part 1: Change From Baseline in NPI Domain Score at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[44]	0 ^[45]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[44] - For part 1, the efficacy endpoints became exploratory in nature.
[45] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104

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End point title

Part 1: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[46]	0 ^[47]
Units: Units on the Scale
arithmetic mean (standard deviation)	( )	( )

Notes
[46] - For part 1, the efficacy endpoints became exploratory in nature.
[47] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104

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End point title

Part 1: Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[48]	0 ^[49]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[48] - For part 1, the efficacy endpoints became exploratory in nature.
[49] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104

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End point title

Part 1: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[50]	0 ^[51]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[50] - For part 1, the efficacy endpoints became exploratory in nature.
[51] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change from Baseline in Dependence Scale (DS) at Week 104

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End point title

Part 1: Change from Baseline in Dependence Scale (DS) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[52]	0 ^[53]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[52] - For part 1, the efficacy endpoints became exploratory in nature.
[53] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Lite) Scale at Week 104

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End point title

Part 1: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Lite) Scale at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[54]	0 ^[55]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[54] - For part 1, the efficacy endpoints became exploratory in nature.
[55] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104

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End point title

Part 1: Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[56]	0 ^[57]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[56] - For part 1, the efficacy endpoints became exploratory in nature.
[57] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Time to Clinical Decline

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End point title

Part 1: Time to Clinical Decline

End point description

End point type

Other pre-specified

End point timeframe

Baseline up to Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[58]	0 ^[59]
Units: Weeks
median (full range (min-max))	( to )	( to )

Notes
[58] - For part 1, the efficacy endpoints became exploratory in nature.
[59] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104

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End point title

Part 1: Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104

End point description

End point type

Other pre-specified

End point timeframe

Baseline, Week 104

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[60]	0 ^[61]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[60] - For part 1, the efficacy endpoints became exploratory in nature.
[61] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Other pre-specified: Part 1: Percentage of participants with ADAS-Cog Response

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End point title

Part 1: Percentage of participants with ADAS-Cog Response

End point description

End point type

Other pre-specified

End point timeframe

Baseline up to Week 152

End point values	Part 1: Placebo	Part 1: Gantenerumab
Number of subjects analysed	0 ^[62]	0 ^[63]
Units: Units on the scale
arithmetic mean (standard deviation)	( )	( )

Notes
[62] - For part 1, the efficacy endpoints became exploratory in nature.
[63] - For part 1, the efficacy endpoints became exploratory in nature.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 52 weeks after the last dose of study drug (up to 7 years)

Adverse event reporting additional description

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

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Part 1: Placebo

Reporting group description

Participants received matching placebo by SC injection Q4W up to 100 weeks during Part 1 of the study.

Reporting group title

Part 1: Gantenerumab

Reporting group description

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.

Reporting group title

Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg

Reporting group description

Reporting group title

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

Reporting group description

Serious adverse events	Part 1: Placebo	Part 1: Gantenerumab	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Total subjects affected by serious adverse events
subjects affected / exposed	53 / 195 (27.18%)	61 / 192 (31.77%)	29 / 117 (24.79%)	41 / 108 (37.96%)
number of deaths (all causes)	11	8	8	5
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebellar tumour
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Colon cancer
subjects affected / exposed	2 / 195 (1.03%)	0 / 192 (0.00%)	2 / 117 (1.71%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Invasive lobular breast carcinoma
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Ovarian epithelial cancer
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of pharynx
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm rupture
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Giant cell arteritis
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cyst
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic shock
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung infiltration
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillar hypertrophy
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Affective disorder
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aggression
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Agitation
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychotic symptom
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide threat
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Electrocardiogram abnormal
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest injury
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Comminuted fracture
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	3 / 195 (1.54%)	5 / 192 (2.60%)	0 / 117 (0.00%)	3 / 108 (2.78%)
occurrences causally related to treatment / all	0 / 3	0 / 5	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	1 / 195 (0.51%)	2 / 192 (1.04%)	1 / 117 (0.85%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	1 / 117 (0.85%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Jaw fracture
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Optic nerve injury
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	2 / 195 (1.03%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	2 / 195 (1.03%)	2 / 192 (1.04%)	1 / 117 (0.85%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	1 / 2	1 / 2	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Traumatic intracranial haemorrhage
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 195 (0.00%)	3 / 192 (1.56%)	0 / 117 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 195 (0.51%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Myocardial infarction
subjects affected / exposed	2 / 195 (1.03%)	1 / 192 (0.52%)	1 / 117 (0.85%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 1
Nervous system disorders
ARIA-E
subjects affected / exposed	2 / 195 (1.03%)	2 / 192 (1.04%)	2 / 117 (1.71%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	2 / 2	3 / 3	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ARIA-H
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain stem infarction
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haematoma
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral venous sinus thrombosis
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Dementia Alzheimer's type
subjects affected / exposed	2 / 195 (1.03%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Dementia of the Alzheimer's type, with delusions
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 195 (0.51%)	2 / 192 (1.04%)	1 / 117 (0.85%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	1 / 1	0 / 2	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukoencephalopathy
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neurotoxicity
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychomotor hyperactivity
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 195 (1.03%)	2 / 192 (1.04%)	1 / 117 (0.85%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	2 / 195 (1.03%)	0 / 192 (0.00%)	2 / 117 (1.71%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertebral artery dissection
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertebrobasilar stroke
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Ocular hypertension
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulum intestinal haemorrhagic
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Enteritis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Faeces discoloured
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendiceal abscess
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colonic abscess
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periodontitis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	1 / 117 (0.85%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 195 (1.54%)	1 / 192 (0.52%)	2 / 117 (1.71%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	3 / 195 (1.54%)	0 / 192 (0.00%)	3 / 117 (2.56%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Shunt infection
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis bacterial
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	3 / 195 (1.54%)	3 / 192 (1.56%)	3 / 117 (2.56%)	2 / 108 (1.85%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 195 (0.51%)	0 / 192 (0.00%)	0 / 117 (0.00%)	0 / 108 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 195 (0.00%)	1 / 192 (0.52%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 195 (0.00%)	2 / 192 (1.04%)	0 / 117 (0.00%)	1 / 108 (0.93%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1: Placebo	Part 1: Gantenerumab	Part 2 (OLE treatment): Placebo switched to Gant to 1200 mg	Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	147 / 195 (75.38%)	159 / 192 (82.81%)	94 / 117 (80.34%)	91 / 108 (84.26%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	12 / 195 (6.15%)	16 / 192 (8.33%)	5 / 117 (4.27%)	8 / 108 (7.41%)
occurrences all number	15	21	7	9
Fall
subjects affected / exposed	28 / 195 (14.36%)	35 / 192 (18.23%)	16 / 117 (13.68%)	22 / 108 (20.37%)
occurrences all number	44	69	25	41
Skin abrasion
subjects affected / exposed	6 / 195 (3.08%)	12 / 192 (6.25%)	3 / 117 (2.56%)	5 / 108 (4.63%)
occurrences all number	7	17	3	10
Vascular disorders
Hypertension
subjects affected / exposed	13 / 195 (6.67%)	13 / 192 (6.77%)	4 / 117 (3.42%)	5 / 108 (4.63%)
occurrences all number	13	15	4	5
Nervous system disorders
ARIA-E
subjects affected / exposed	32 / 195 (16.41%)	42 / 192 (21.88%)	29 / 117 (24.79%)	30 / 108 (27.78%)
occurrences all number	42	70	35	51
ARIA-H
subjects affected / exposed	30 / 195 (15.38%)	36 / 192 (18.75%)	19 / 117 (16.24%)	23 / 108 (21.30%)
occurrences all number	39	42	23	27
Dizziness
subjects affected / exposed	18 / 195 (9.23%)	17 / 192 (8.85%)	13 / 117 (11.11%)	6 / 108 (5.56%)
occurrences all number	24	26	13	6
Headache
subjects affected / exposed	29 / 195 (14.87%)	22 / 192 (11.46%)	15 / 117 (12.82%)	12 / 108 (11.11%)
occurrences all number	38	44	18	24
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	49 / 195 (25.13%)	52 / 192 (27.08%)	48 / 117 (41.03%)	44 / 108 (40.74%)
occurrences all number	284	322	281	280
Oedema peripheral
subjects affected / exposed	2 / 195 (1.03%)	10 / 192 (5.21%)	1 / 117 (0.85%)	8 / 108 (7.41%)
occurrences all number	2	11	1	9
Pyrexia
subjects affected / exposed	4 / 195 (2.05%)	7 / 192 (3.65%)	2 / 117 (1.71%)	6 / 108 (5.56%)
occurrences all number	4	9	2	8
Gastrointestinal disorders
Constipation
subjects affected / exposed	14 / 195 (7.18%)	16 / 192 (8.33%)	6 / 117 (5.13%)	0 / 108 (0.00%)
occurrences all number	15	20	7	15
Diarrhoea
subjects affected / exposed	23 / 195 (11.79%)	11 / 192 (5.73%)	11 / 117 (9.40%)	8 / 108 (7.41%)
occurrences all number	27	18	14	13
Nausea
subjects affected / exposed	15 / 195 (7.69%)	10 / 192 (5.21%)	3 / 117 (2.56%)	4 / 108 (3.70%)
occurrences all number	24	11	9	4
Vomiting
subjects affected / exposed	11 / 195 (5.64%)	14 / 192 (7.29%)	6 / 117 (5.13%)	6 / 108 (5.56%)
occurrences all number	16	18	11	7
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	9 / 195 (4.62%)	12 / 192 (6.25%)	4 / 117 (3.42%)	5 / 108 (4.63%)
occurrences all number	9	12	4	5
Psychiatric disorders
Agitation
subjects affected / exposed	13 / 195 (6.67%)	18 / 192 (9.38%)	9 / 117 (7.69%)	8 / 108 (7.41%)
occurrences all number	16	21	10	9
Anxiety
subjects affected / exposed	13 / 195 (6.67%)	13 / 192 (6.77%)	5 / 117 (4.27%)	6 / 108 (5.56%)
occurrences all number	13	14	5	6
Depression
subjects affected / exposed	17 / 195 (8.72%)	13 / 192 (6.77%)	8 / 117 (6.84%)	2 / 108 (1.85%)
occurrences all number	17	14	8	2
Insomnia
subjects affected / exposed	12 / 195 (6.15%)	15 / 192 (7.81%)	7 / 117 (5.98%)	5 / 108 (4.63%)
occurrences all number	15	16	8	5
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	14 / 195 (7.18%)	13 / 192 (6.77%)	8 / 117 (6.84%)	7 / 108 (6.48%)
occurrences all number	15	23	8	10
Back pain
subjects affected / exposed	20 / 195 (10.26%)	17 / 192 (8.85%)	8 / 117 (6.84%)	5 / 108 (4.63%)
occurrences all number	21	19	9	5
Neck pain
subjects affected / exposed	6 / 195 (3.08%)	2 / 192 (1.04%)	6 / 117 (5.13%)	1 / 108 (0.93%)
occurrences all number	6	2	6	1
Infections and infestations
Bronchitis
subjects affected / exposed	10 / 195 (5.13%)	10 / 192 (5.21%)	6 / 117 (5.13%)	5 / 108 (4.63%)
occurrences all number	13	11	9	6
Influenza
subjects affected / exposed	8 / 195 (4.10%)	14 / 192 (7.29%)	4 / 117 (3.42%)	10 / 108 (9.26%)
occurrences all number	10	19	4	12
Nasopharyngitis
subjects affected / exposed	27 / 195 (13.85%)	23 / 192 (11.98%)	13 / 117 (11.11%)	11 / 108 (10.19%)
occurrences all number	35	31	14	15
Upper respiratory tract infection
subjects affected / exposed	20 / 195 (10.26%)	7 / 192 (3.65%)	10 / 117 (8.55%)	3 / 108 (2.78%)
occurrences all number	30	12	13	5
Urinary tract infection
subjects affected / exposed	17 / 195 (8.72%)	18 / 192 (9.38%)	11 / 117 (9.40%)	7 / 108 (6.48%)
occurrences all number	20	28	13	14

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Oct 2014

A. Protocol was amended to allow for higher doses of gantenerumab to be examined in an open-label extension and the positron emission tomography (PET) substudy protocol was amended to reflect these changes and to allow subjects participating in the PET substudy to continue their yearly PET scans according to the open label schedule. B. Overview section was updated to explain overall changes. C. Update was made in rationale of study to explain the need for up-titration. D. Study design was updated to allow for transition into open label. Also, to update the number of subjects, treatment allocation and to delete the arterial blood sampling. E. Number of subjects and inclusion criteria was updated F. Schedule of Assessment and Procedures was updated. G. Need for an additional scan was updated in preparation and administration of the radioligand. H. Warnings and precautions, sample size information and overall statistical plan was updated. I. Ongoing review of the PET data by Sponsor included in interim review of study results.

27 Oct 2015

A. Protocol body was updated to clarify Part 1 from Part 2. B. Protocol was amended to allow for higher doses of gantenerumab to be examined in an open-label extension and to achieve higher dosing using an APOE ε4-based titration schedule and corresponding magnetic resonance imaging monitoring. C. Screening examination and eligibility screening form were updated. D. Update was made to reflect the abbreviated rescreening visit can be combined with baseline visit as long as all procedures required at screening and Baseline are performed. E. Serology requirements for the screening and re-screening visits were specified. F. Schedule of assessments was updated. G. Roche reporting requirements were updated.

02 Dec 2017

A. Protocol was amended to allow subjects the option to continue receiving open-label gantenerumab until the end of 2020. B. The number of studies in which gantenerumab is investigated were updated in background on Gantenerumab. C. The period of review for independent data monitoring committee has been clarified. D. The Cardiac-PET substudy has been updated to reflect updated status. E. Update was made to reflect MMSE is the only efficacy outcome measure assessed during additional years of part 2. F. Removed the cardiac PET substudy because the substudy has been stopped. G. Pharmacokinetic sampling in case of amyloid-related imaging abnormality findings has been clarified. H. Medical monitor information has been updated to reflect the change in Medical Monitor. I. The reporting of the term “sudden death” has been updated. J. Event reporting for hospitalization has been clarified. K. The process for reviewing and handling protocol deviations has been updated. L. Appendix 2 has been updated to indicate assessments collected during the additional years of OLE.

28 Feb 2020

A. Protocol was amended to allow participants who complete dosing visits in study WN28745 to enroll in an OLE study (WN41874) without any unnecessary dosing gap, and to enable the use of leftover plasma samples, collected for PK and ADA analysis, for exploratory biomarker research. B. Update was made to clarify that amyloid-related imaging abnormalities (both edema/effusion and hemosiderin depositions) and injection-site reactions are identified risks for gantenerumab and to enable participants to enroll in study WN41874 (open-label rollover study) to continue to receive gantenerumab for 2 more years. Participants who enroll in study WN41874 will not undergo follow-up assessments 16 weeks after their last dose (Follow–Up 2 visit). C. Positron emission tomography tracers used in the substudies associated in this substudy are included as investigational medicinal products (IMPs) or non-IMPs. D. Update was made to enable the use of leftover plasma samples, collected for PK and ADA analysis, for exploratory biomarker research and to clarify the timing of follow-up visits for Part 1 versus Part 2. E. Medical Monitor contact information was updated. F. Documents to be used for reference safety information for the PET tracers have been specified. G. Appendix 2 has been corrected to clarify that treatment is not to be administered at the Follow-Up 1 visit. H. Appendix 2 has been updated to add an optional lumbar puncture at Week 104 for all participants.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

As the participants transitioned early to OLE, most participants did not reach the primary analysis timepoint (Week 104). Hence, the efficacy endpoints for Part 1 became exploratory in nature.

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Clinical trials

Clinical Trial Results: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs)

Primary: Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs)

Primary: Part 2: Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs)

Primary: Part 2: Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs)

Primary: Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment

Primary: Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment

Secondary: Part 1: Percentage of Participants With AEs, SAEs

Secondary: Part 1: Percentage of Participants With AEs, SAEs

Secondary: Part 1: Percentage of Participants with Treatment-emergent ADAs

Secondary: Part 1: Percentage of Participants with Treatment-emergent ADAs

Secondary: Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints

Secondary: Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints

Secondary: Part 1: Percentage of Participants with Adverse Events Leading to Discontinuation of Treatment

Secondary: Part 1: Percentage of Participants with Adverse Events Leading to Discontinuation of Treatment

Secondary: Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104

Secondary: Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104

Secondary: Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104

Secondary: Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104

Secondary: Part 2: Percent Change From Baseline in Cortical Thickness at Week 104

Secondary: Part 2: Percent Change From Baseline in Cortical Thickness at Week 104

Secondary: Part 2: Ventricular Volume as Measured by MRI at Week 104

Secondary: Part 2: Ventricular Volume as Measured by MRI at Week 104

Secondary: Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints

Secondary: Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints

Secondary: Part 2: Change from Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants

Secondary: Part 2: Change from Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants

Other pre-specified: Part 1: Mean Change from Baseline in Alzheimer's Disease Activity Scale-Cognitive Subscale 13 (ADAS-Cog13) Scores at Week 104

Other pre-specified: Part 1: Mean Change from Baseline in Alzheimer's Disease Activity Scale-Cognitive Subscale 13 (ADAS-Cog13) Scores at Week 104

Other pre-specified: Part 1: Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104

Other pre-specified: Part 1: Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104

Other pre-specified: Part 1: Percentage Change From Baseline in Total Tau (t-tau) in CSF at Week 104

Other pre-specified: Part 1: Percentage Change From Baseline in Total Tau (t-tau) in CSF at Week 104

Other pre-specified: Part 1: Percentage Change From Baseline in Abeta 1-42 levels in CSF at Week 104

Other pre-specified: Part 1: Percentage Change From Baseline in Abeta 1-42 levels in CSF at Week 104

Other pre-specified: Part 1: Percentage Change From Baseline in phosphorylated tau [p-tau] in CSF at Week 104

Other pre-specified: Part 1: Percentage Change From Baseline in phosphorylated tau [p-tau] in CSF at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Hippocampal Volume at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Hippocampal Volume at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Whole Brain Volume at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Whole Brain Volume at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Cortical Thickness at Week 104

Other pre-specified: Part 1: Percent Change From Baseline in Cortical Thickness at Week 104

Other pre-specified: Part 1: Ventricular Volume as Measured by MRI at Week 104

Other pre-specified: Part 1: Ventricular Volume as Measured by MRI at Week 104

Other pre-specified: Part 1: Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104

Other pre-specified: Part 1: Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104

Other pre-specified: Part 1: Change From Baseline in CDR Sum of Boxes (SB) at Week 104

Other pre-specified: Part 1: Change From Baseline in CDR Sum of Boxes (SB) at Week 104

Other pre-specified: Part 1: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104

Other pre-specified: Part 1: Change From Baseline in NPI Domain Score at Week 104

Other pre-specified: Part 1: Change From Baseline in NPI Domain Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104

Other pre-specified: Part 1: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104

Other pre-specified: Part 1: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104

Other pre-specified: Part 1: Change from Baseline in Dependence Scale (DS) at Week 104

Other pre-specified: Part 1: Change from Baseline in Dependence Scale (DS) at Week 104

Other pre-specified: Part 1: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Lite) Scale at Week 104

Other pre-specified: Part 1: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Lite) Scale at Week 104

Other pre-specified: Part 1: Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104

Other pre-specified: Part 1: Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104

Other pre-specified: Part 1: Time to Clinical Decline

Other pre-specified: Part 1: Time to Clinical Decline

Other pre-specified: Part 1: Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104

Other pre-specified: Part 1: Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104

Other pre-specified: Part 1: Percentage of participants with ADAS-Cog Response

Other pre-specified: Part 1: Percentage of participants with ADAS-Cog Response

Clinical Trial Results:
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients