Scarlet Road

CompletedPhase 3Results posted

A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment

Lead sponsor

Hoffmann-La Roche

Asset

Gantenerumab

Listed sites

139

Recruiting sites

Enrollment

799

actual

Study population

Alzheimer’s disease

Key I/E criteria

•prodromal AD•MMSE 24•Study partner/caregiver required

Primary endpoints

•Clinical Dementia Rating-Sum of Boxes (CDR-SB)•Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2010-019895-66

NCT IDNCT01224106

Org study IDWN25203

Timeline

Milestones

Study first posted2010-10-19estimated

Study start2010-11-30actual

Primary completion2020-09-10actual

Study completion2020-09-10actual

Last update posted2021-12-13actual

Results first posted2021-12-13actual

Assets

Drug assets

Gantenerumab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Adult participants, 50-85 years of age

•Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors

•Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion

•Has had sufficient education or work experience to exclude mental retardation

•Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of

•Screening Mini Mental State Exam (MMSE) score of 24 or above

Additional inclusion criteria for sub study:

•Able and willing to travel to PET imaging center and complete the planned scanning sessions

•Past and planned exposure to ionizing radiation not exceeding safe and permissible levels

Exclusion criteria

•Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning

•A history of stroke

•A documented history of transient ischemic attack within the last 12 months

•History of schizophrenia, schizoaffective or bipolar disorder

•Currently meets criteria for major depression

•Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)

Additional exclusion criteria for sub study:

•Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months

•Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203

•Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits

Endpoints (56)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Memory

Neuroimaging

Safety / tolerability / PK

Other (unclassified)

Function / daily living

Behavior / neuropsychiatric

Amyloid biomarkers

Global cognition

14 endpoints

Primary/protocol endpoint

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/registry result

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=104 Participants	1.19	1.68
Gantenerumab 105 mg (Parts 1 and 2)n=105 Participants	1.41	2.02
Gantenerumab 225 mg (Parts 1 and 2)n=100 Participants	1.47	1.89

Effect Size-0.04495% CI-0.248 - 0.161p0.6744Mixed Models Analysis

Effect Size-0.08595% CI-0.304 - 0.135p0.4494Mixed Models Analysis

Secondary/protocol endpoint

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=105 Participants	3.68	6.64
Gantenerumab 105 mg (Parts 1 and 2)n=104 Participants	3.52	6.28
Gantenerumab 225 mg (Parts 1 and 2)n=100 Participants	3.97	6.89

Effect Size0.03595% CI-0.179 - 0.250p0.7458Mixed Models Analysis

Effect Size0.04295% CI-0.191 - 0.275p0.723Mixed Models Analysis

Secondary/registry result

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=104 Participants	-2.31	3.23
Gantenerumab 105 mg (Parts 1 and 2)n=105 Participants	-2.46	3.68
Gantenerumab 225 mg (Parts 1 and 2)n=99 Participants	-2.25	3.31

Secondary/registry result

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=21 Participants	5.8	7.3
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=51 Participants	8.9	9.7

Secondary/registry result

Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=21 Participants	3.3	2.4
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=52 Participants	2.8	3.0

Secondary/registry result

Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=21 Participants	8.0	8.2
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=51 Participants	10.4	10.6

Secondary/registry result

Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=22 Participants	-4.3	4.3
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=53 Participants	-4.7	4.6

Memory

10 endpoints

Secondary/protocol endpoint

Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Secondary/registry result

Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (mean), Z-Score	Standard deviation
Placebo (Parts 1 and 2)n=90 Participants	-1.72	2.99
Gantenerumab 105 mg (Parts 1 and 2)n=87 Participants	-1.37	2.74
Gantenerumab 225 mg (Parts 1 and 2)n=80 Participants	-1.4	3.11
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)n=73 Participants	-1.93	3.08

Secondary/registry result

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=100 Participants	-4.05	8.73
Gantenerumab 105 mg (Parts 1 and 2)n=102 Participants	-4.11	8.57
Gantenerumab 225 mg (Parts 1 and 2)n=97 Participants	-6.42	8.45
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)n=79 Participants	-4.05	8.68

Secondary/registry result

Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=104 Participants	0.1	0.29
Gantenerumab 105 mg (Parts 1 and 2)n=105 Participants	0.18	0.36
Gantenerumab 225 mg (Parts 1 and 2)n=100 Participants	0.14	0.33
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)n=83 Participants	0.1	0.31

Secondary/registry result

Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=22 Participants	-7.7	9.3
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=51 Participants	-4.1	8.3

Secondary/registry result

Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=21 Participants	0.6	0.6
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=52 Participants	0.5	0.6

Function / daily living

4 endpoints

Secondary/protocol endpoint

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/protocol endpoint

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Secondary/registry result

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=105 Participants	3.59	4.93
Gantenerumab 105 mg (Parts 1 and 2)n=104 Participants	4.89	6.2
Gantenerumab 225 mg (Parts 1 and 2)n=99 Participants	4.03	5.75
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)n=84 Participants	3.6	4.93

Effect Size-0.19195% CI-0.407 - 0.025p0.0825Mixed Models Analysis

Effect Size0.04395% CI-0.19 - 0.276p0.7171Mixed Models Analysis

Secondary/registry result

Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=22 Participants	8.1	5.3
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=52 Participants	6.8	6.8

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a Scale	Standard deviation
Placebo (Parts 1 and 2)n=103 Participants	0.6	3.22
Gantenerumab 105 mg (Parts 1 and 2)n=105 Participants	0.39	2.57
Gantenerumab 225 mg (Parts 1 and 2)n=99 Participants	0.34	2.84
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)n=82 Participants	0.72	3.35

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

percent change from baseline, improvement

Secondary/registry result

Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage Change	Standard deviation
Placebo (Parts 1 and 2)p-tau (Week 104)n=72 Participants	2.77	20.69
t-tau (Week 104)n=72 Participants	3.43	19.95
Abeta (Week 104)n=69 Participants	4.87	36.14
Gantenerumab 105 mg (Parts 1 and 2)p-tau (Week 104)n=71 Participants	-4.78	11.9
t-tau (Week 104)n=71 Participants	-1.36	12.89
Abeta (Week 104)n=64 Participants	2.45	24.57
Gantenerumab 225 mg (Parts 1 and 2)p-tau (Week 104)n=66 Participants	-7.34	10.09
t-tau (Week 104)n=66 Participants	-2.12	11.01
Abeta (Week 104)n=65 Participants	15.2	45.24
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)p-tau (Week 104)n=56 Participants	2.84	23.19
t-tau (Week 104)n=56 Participants	3.46	22.32
Abeta (Week 104)n=56 Participants	4.3	39.31

p0.9734Mixed Models Analysis

Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.

p0.0629Mixed Models Analysis

Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.

p0.0084Mixed Models Analysis

Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.

p0.0003Mixed Models Analysis

Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.

p0.0903Mixed Models Analysis

Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.

p0.0434Mixed Models Analysis

Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.

Neuroimaging

8 endpoints

Secondary/protocol endpoint

Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 156

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)

Time frame:Baseline, Week 152

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

percent change from baseline, improvement

Secondary/registry result

Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage Change	Standard deviation
Placebo (Parts 1 and 2)HRV (Week 104)n=131 Participants	-7.61	4.03
HLV (Week 104)n=131 Participants	-7.8	4.28
Gantenerumab 105 mg (Parts 1 and 2)HRV (Week 104)n=124 Participants	-7.52	3.96
HLV (Week 104)n=124 Participants	-7.76	3.74
Gantenerumab 225 mg (Parts 1 and 2)HRV (Week 104)n=119 Participants	-7.34	3.84
HLV (Week 104)n=119 Participants	-7.27	3.78
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)HRV (Week 104)n=107 Participants	-7.7	4.01
HLV (Week 104)n=107 Participants	-8.12	4.19

Secondary/registry result

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 156

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage Change	Standard deviation
Placebo (Parts 1 and 2)Cerebellum gray (Week 156)n=6 Participants	6.26	9.1
Whole Cerebellum (Week 156)n=6 Participants	5.41	7.13
Composite White Matter (Week 156)n=6 Participants	2.75	3.18
Subcortical White Matter (Week 156)n=6 Participants	4.83	4.95
Pons (Week 156)n=6 Participants	1.72	2.51
Composite Reference (Week 156)n=6 Participants	4.5	3.48
Gantenerumab 105 mg (Parts 1 and 2)Cerebellum gray (Week 156)n=4 Participants	2.7	10.59
Whole Cerebellum (Week 156)n=4 Participants	2.07	8.65
Composite White Matter (Week 156)n=4 Participants	-0.87	2.95
Subcortical White Matter (Week 156)n=4 Participants	1.69	4.45
Pons (Week 156)n=4 Participants	-2.83	3.39
Composite Reference (Week 156)n=4 Participants	1.19	5.63
Gantenerumab 225 mg (Parts 1 and 2)Cerebellum gray (Week 156)n=10 Participants	-8.36	9.11
Whole Cerebellum (Week 156)n=10 Participants	-8.44	8.06
Composite White Matter (Week 156)n=10 Participants	-4.86	6.35
Subcortical White Matter (Week 156)n=10 Participants	-0.42	8.26
Pons (Week 156)n=10 Participants	-6.99	5.65
Composite Reference (Week 156)n=10 Participants	-6.75	6.1
Placebo Match Gantenerumab 225 mg (Parts 1 and 2)Cerebellum gray (Week 156)n=4 Participants	5.95	11.13
Whole Cerebellum (Week 156)n=4 Participants	5.17	8.66
Composite White Matter (Week 156)n=4 Participants	3.07	2.07
Subcortical White Matter (Week 156)n=4 Participants	4.59	0.55
Pons (Week 156)n=4 Participants	2.1	2.73
Composite Reference (Week 156)n=4 Participants	4.46	4.49

Secondary/registry result

Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)

Time frame:Baseline, Week 152

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage Change	Standard deviation
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])HRV (Week 152)n=18 Participants	16.7	8.4
HLV (Week 152)n=18 Participants	16.2	13.0
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])HRV (Week 152)n=51 Participants	16.1	8.2
HLV (Week 152)n=51 Participants	18.0	8.9

Secondary/registry result

Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage Change	Standard deviation
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])Cerebellum gray (Week 156)n=2 Participants	-0.2	0.2
Composite Reference (Week 156)n=2 Participants	-41.4	29.9

Safety / tolerability / PK

8 endpoints

Primary/protocol endpoint

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)

Time frame:Baseline up until a maximum of 5 years

event count, event

Primary/registry result

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)

Time frame:Baseline up until a maximum of 5 years

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])AEsn=49 Participants	46	-
SAEsn=49 Participants	18	-
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])AEsn=105 Participants	100	-
SAEsn=105 Participants	28	-

Secondary/protocol endpoint

Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)

Time frame:Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101

concentration, descriptive

Secondary/protocol endpoint

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)

Time frame:Baseline up until a maximum of 4.5 years

event count, event

Secondary/protocol endpoint

Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)

Time frame:Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101

concentration, descriptive

Secondary/registry result

Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)

Time frame:Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101

concentration, descriptive

Posted result

Group	Value (mean), µg/ml (micrograms per milliliter)	Standard deviation
Gantenerumab 105 mg (Parts 1 and 2)Week 1 (Post-Dose)n=239 Participants	3.56	2.36
Week 8 (Pre-Dose)n=237 Participants	2.87	1.84
Week 20 (Pre-Dose)n=228 Participants	3.7	2.15
Week 44 (Pre-Dose)n=212 Participants	4.08	2.44
Week 53 (Post-Dose)n=195 Participants	6.77	3.94
Week 68 (Pre-Dose)n=165 Participants	3.95	2.35
Week 100 (Pre-Dose)n=98 Participants	4.35	2.34
Week 101 (Post-Dose)n=95 Participants	7.32	3.53
Gantenerumab 225 mg (Parts 1 and 2)Week 1 (Post-Dose)n=227 Participants	7.4	4.28
Week 8 (Pre-Dose)n=225 Participants	5.92	3.16
Week 20 (Pre-Dose)n=220 Participants	7.66	4.14
Week 44 (Pre-Dose)n=199 Participants	8.22	4.51
Week 53 (Post-Dose)n=185 Participants	15	9.34
Week 68 (Pre-Dose)n=155 Participants	8.91	4.86
Week 100 (Pre-Dose)n=86 Participants	9.4	4.69
Week 101 (Post-Dose)n=77 Participants	16.63	7.96

Secondary/registry result

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)

Time frame:Baseline up until a maximum of 4.5 years

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebo (Parts 1 and 2)AEsn=266 Participants	250	-
SAEsn=266 Participants	55	-
Gantenerumab 105 mg (Parts 1 and 2)AEsn=271 Participants	241	-
SAEsn=271 Participants	48	-
Gantenerumab 225 mg (Parts 1 and 2)AEsn=260 Participants	240	-
SAEsn=260 Participants	46	-

Secondary/registry result

Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)

Time frame:Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101

concentration, descriptive

Posted result

Group	Value (mean), µg/ml (micrograms per milliliter)	Standard deviation
Gantenerumab 1200 mg (Part 3 Open-Label Extension [OLE])Week 64 (Pre-Dose)n=99 Participants	33.0	21.7
Week 100 (Pre-Dose)n=89 Participants	39.2	22.7
Week 101 (Post-Dose)n=88 Participants	80.5	37.8
Week 104 (Pre-Dose)n=91 Participants	40.5	22.5
Week 136 (Pre-Dose)n=83 Participants	45.2	22.4
Week 156 (Pre-Dose)n=93 Participants	39.6	28.2
Week 208 (Pre-Dose)n=26 Participants	37.1	29.2

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

time to event, event

Secondary/protocol endpoint/low confidence

Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)

Time frame:Baseline up until a maximum of 4.5 years

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Time to Onset of Dementia at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

time to event, event

Secondary/protocol endpoint/low confidence

Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)

Time frame:Baseline up until a maximum of 5 years

threshold achievement, improvement

Secondary/registry result/low confidence

Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)

Time frame:Baseline, Week 104

time to event, event

Posted result

Group	Value (median), Days	Reported bounds
Placebo (Parts 1 and 2)n=91 Participants	63.64	-56.63 - 69.82
Gantenerumab 105 mg (Parts 1 and 2)n=95 Participants	62.98	-56.00 - 69.16
Gantenerumab 225 mg (Parts 1 and 2)n=91 Participants	70.64	-63.34 - 76.75

Secondary/registry result/low confidence

Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)

Time frame:Baseline up until a maximum of 4.5 years

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
Placebo (Parts 1 and 2)Baseline ADAsn=259 Participants	5.8	-
Treatment Emergent ADAsn=259 Participants	5.0	-
Gantenerumab 105 mg (Parts 1 and 2)Baseline ADAsn=266 Participants	7.5	-
Treatment Emergent ADAsn=258 Participants	7.0	-
Gantenerumab 225 mg (Parts 1 and 2)Baseline ADAsn=256 Participants	5.5	-
Treatment Emergent ADAsn=250 Participants	6.4	-

Secondary/registry result/low confidence

Time to Onset of Dementia at Week 156 (OLE Phase)

Time frame:Baseline, Week 156

time to event, event

Posted result

Group	Value (median), Days	Reported bounds
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])n=3 Participants	38.18	-9.90 - 66.97
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])n=14 Participants	50.82	-32.04 - 66.87

Secondary/registry result/low confidence

Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)

Time frame:Baseline up until a maximum of 5 years

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])Baseline ADAsn=49 Participants	2.0	-
Treatment Emergent ADAsn=46 Participants	2.2	-
Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])Baseline ADAsn=104 Participants	5.8	-
Treatment Emergent ADAsn=102 Participants	2.9	-

Publications (5)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.