TerminatedPhase 3Results posted

Efficacy and Safety Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease

Lead sponsor

Hoffmann-La Roche

Asset

Gantenerumab

Listed sites

172

Recruiting sites

Enrollment

1,053

actual

Study population

Alzheimer’s disease

Key I/E criteria

•prodromal AD•Amyloid biomarker required (PET/CSF)•Tau biomarker required (PET/CSF)•MMSE ≥22•Study partner/caregiver required

Primary endpoint

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

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 number2017-001364-38

NCT IDNCT03444870

Org study IDWN29922

Timeline

Milestones

Study first posted2018-02-23actual

Study start2018-06-06actual

Primary completion2022-12-28actual

Study completion2023-02-17actual

Last update posted2024-01-30actual

Results first posted2024-01-30actual

Assets

Drug assets

Gantenerumab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Key Inclusion criteria:

•Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment)

•Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid PET scan

•Demonstrated abnormal memory function

•MMSE score greater than or equal to 22 (≥ 22)

•Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0

•Availability of a reliable study partner who accepts to participate in study procedures throughout the 2 years duration of study

•If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening and until randomization

•For enrollment in the China extension, patients must have residence in mainland China, Hong Kong, or Taiwan and be of Chinese ancestry

•For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

Exclusion criteria

•Any evidence of a condition other than AD that may affect cognition

•History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder

•History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function

•History or presence of clinically evident cerebrovascular disease

•History or presence of posterior reversible encephalopathy syndrome

•History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack

•History of severe, clinically significant CNS trauma

•History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition

•Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae

•History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits

•At risk for suicide in the opinion of the investigator

•Alcohol and/or substance abuse or dependants in past 2 years

•Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

•Any contraindications to brain MRI

•Unstable or clinically significant cardiovascular, kidney or liver disease

•Uncontrolled hypertension

•Unstable or clinically significant cardiovascular disease

•Abnormal thyroid function

•Patients with evidence of folic acid deficiency

Exclusion for Open-Label Extension (OLE):

•Discontinued from study treatment during the double-blind treatment period

•Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment

•Participation in the OLE deemed inappropriate by the investigator

•Presence of ARIA-E findings at the Week 116 MRI scan

Endpoints (76)

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

Amyloid biomarkers

Global cognition

Other (unclassified)

Function / daily living

Memory

Behavior / neuropsychiatric

Tau biomarkers

Neurodegeneration biomarkers

Executive function / language

Safety / tolerability / PK

Global cognition

12 endpoints

Primary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB

Time frame:Baseline, Week 116

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

change from baseline, improvement

Primary/protocol endpoint

China Extension: DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB

Time frame:Baseline, Week 116

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

change from baseline, improvement

Primary/registry result

DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB

Time frame:Baseline, Week 116

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

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=485 Participants	3.65	0.16
Global - DBT Period: Gantenerumabn=499 Participants	3.35	0.14

Difference in adjusted mean-0.3195% CI-0.66 - 0.05p0.0954ANCOVA

Primary/registry result

China Extension: DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB

Time frame:Baseline, Week 116

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

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score

Time frame:Baseline, Week 116

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog13 Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score

Time frame:Baseline, Week 116

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=480 Participants	9.82	0.57
Global - DBT Period: Gantenerumabn=497 Participants	8.57	0.47

Difference in adjusted mean-1.2595% CI-2.52 - 0.02p0.0544ANCOVA

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score

Time frame:Baseline, Week 116

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=485 Participants	-5.18	0.25
Global - DBT Period: Gantenerumabn=499 Participants	-4.86	0.23

Difference in adjusted mean0.3295% CI-0.28 - 0.93p0.2904ANCOVA

Secondary/registry result

China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog13 Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/registry result

China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score

Time frame:Baseline, Week 116

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Memory

8 endpoints

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Change From Baseline to Week 116 in the Coding (DSST) Subtest

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=481 Participants	8.42	0.52
Global - DBT Period: Gantenerumabn=498 Participants	7.44	0.43

Difference in adjusted mean-0.9795% CI-2.14 - 0.20p0.1036ANCOVA

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest

Time frame:Baseline, Week 116

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=480 Participants	-6.47	0.64
Global - DBT Period: Gantenerumabn=498 Participants	-6.27	0.54

Difference in adjusted mean0.2095% CI-1.35 - 1.74p0.8030ANCOVA

Secondary/registry result

China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score

Time frame:Baseline, Week 116

ADAS-Cog

change from baseline, improvement

Secondary/registry result

China - DBT Period: Change From Baseline to Week 116 in the Coding (DSST) Subtest

Time frame:Baseline, Week 116

change from baseline, improvement

Executive function / language

2 endpoints

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score

Time frame:Baseline, Week 116

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=481 Participants	-3.46	0.31
Global - DBT Period: Gantenerumabn=499 Participants	-3.53	0.30

Difference in adjusted mean-0.0795% CI-0.79 - 0.65p0.8468ANCOVA

Function / daily living

10 endpoints

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score

Time frame:Baseline, Week 116

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score

Time frame:Baseline, Week 116

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Change From Baseline to Week 116 in FAQ Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score

Time frame:Baseline, Week 116

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=479 Participants	-12.32	0.68
Global - DBT Period: Gantenerumabn=497 Participants	-11.21	0.60

Difference in adjusted mean1.1195% CI-0.48 - 2.70p0.1729ANCOVA

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score

Time frame:Baseline, Week 116

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=479 Participants	8.13	0.33
Global - DBT Period: Gantenerumabn=498 Participants	7.28	0.30

Difference in adjusted mean-0.8695% CI-1.68 - -0.03p0.0425ANCOVA

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score

Time frame:Baseline, Week 116

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=479 Participants	-10.80	0.56
Global - DBT Period: Gantenerumabn=497 Participants	-9.80	0.51

Difference in adjusted mean1.0095% CI-0.34 - 2.34p0.1439ANCOVA

Secondary/registry result

China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score

Time frame:Baseline, Week 116

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

China - DBT Period: Change From Baseline to Week 116 in FAQ Score

Time frame:Baseline, Week 116

change from baseline, improvement

Behavior / neuropsychiatric

6 endpoints

Secondary/protocol endpoint

DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/protocol endpoint

China - DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Secondary/protocol endpoint

OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Secondary/registry result

DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: PlaceboSuicidal Ideation: Passiven=467 Participants	13	-
Suicidal Ideation: Active-Nonspecificn=467 Participants	1	-
Suicidal Ideation: Active-Method, But No Intent or Plann=467 Participants	6	-
Suicidal Ideation: Active-Method and Intent, But No Plann=467 Participants	2	-
Suicidal Ideation: Active-Method, Intent, and Plann=467 Participants	2	-
Suicidal Ideation: No Eventn=467 Participants	443	-
Suicidal Behavior: Interrupted Attemptn=467 Participants	0	-
Suicidal Behavior: No Eventn=467 Participants	467	-
Self-injurious Behavior Without Suicidal Intent: No Eventn=467 Participants	467	-
Global - DBT Period: GantenerumabSuicidal Ideation: Passiven=489 Participants	17	-
Suicidal Ideation: Active-Nonspecificn=489 Participants	3	-
Suicidal Ideation: Active-Method, But No Intent or Plann=489 Participants	3	-
Suicidal Ideation: Active-Method and Intent, But No Plann=489 Participants	0	-
Suicidal Ideation: Active-Method, Intent, and Plann=489 Participants	0	-
Suicidal Ideation: No Eventn=489 Participants	466	-
Suicidal Behavior: Interrupted Attemptn=489 Participants	1	-
Suicidal Behavior: No Eventn=489 Participants	488	-
Self-injurious Behavior Without Suicidal Intent: No Eventn=489 Participants	489	-

Secondary/registry result

China - DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
China Extension - DBT Period: PlaceboSuicidal Ideation: Passiven=25 Participants	1	-
Suicidal Ideation: Active-Nonspecific (no method, intent, or plan)n=25 Participants	0	-
Suicidal Ideation: Active-Method and intent, but no plann=25 Participants	1	-
Suicidal Ideation: No Eventn=25 Participants	23	-
Suicidal Behavior: No Eventn=25 Participants	25	-
Self-injurious Behavior Without Suicidal Intent: No eventn=25 Participants	25	-
China Extension - DBT Period: GantenerumabSuicidal Ideation: Passiven=30 Participants	1	-
Suicidal Ideation: Active-Nonspecific (no method, intent, or plan)n=30 Participants	1	-
Suicidal Ideation: Active-Method and intent, but no plann=30 Participants	0	-
Suicidal Ideation: No Eventn=30 Participants	28	-
Suicidal Behavior: No Eventn=30 Participants	30	-
Self-injurious Behavior Without Suicidal Intent: No eventn=30 Participants	30	-

Secondary/registry result

OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - OLE Period: Placebo (DBT) to GantenerumabSuicidal Ideation: Active-Method, but no intent or plann=6 Participants	0	-
Suicidal Ideation: No Eventn=6 Participants	6	-
Suicidal Behavior: No Eventn=6 Participants	6	-
Self-injurious Behavior Without Suicidal Intent: No eventn=6 Participants	6	-
Global - OLE Period: Gantenerumab (DBT) to GantenerumabSuicidal Ideation: Active-Method, but no intent or plann=19 Participants	1	-
Suicidal Ideation: No Eventn=19 Participants	18	-
Suicidal Behavior: No Eventn=19 Participants	19	-
Self-injurious Behavior Without Suicidal Intent: No eventn=19 Participants	19	-

Amyloid biomarkers

14 endpoints

Secondary/protocol endpoint

DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/protocol endpoint

DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants

Time frame:Baseline, Week 116

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Secondary/protocol endpoint

China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Secondary/protocol endpoint

OLE Period: Number of Participants With at Least One ARIA-H MRI Finding

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Secondary/protocol endpoint

OLE Period: Number of Participants With at Least One ARIA-E MRI Finding

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Secondary/registry result

DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: Placebon=476 Participants	5	-
Global - DBT Period: Gantenerumabn=497 Participants	105	-

Secondary/registry result

DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: Placebon=476 Participants	6	-
Global - DBT Period: Gantenerumabn=497 Participants	40	-

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants

Time frame:Baseline, Week 116

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard error
Global - DBT Period: Placebon=41 Participants	9.06	3.046
Global - DBT Period: Gantenerumabn=49 Participants	-57.38	2.841

Difference in adjusted means-66.4495% CI-74.71 - -58.16p<.0001Mixed Model for Repeated Measures

Secondary/registry result

China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
China Extension - DBT Period: Placebon=33 Participants	1	-
China Extension - DBT Period: Gantenerumabn=35 Participants	4	-

Secondary/registry result

China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
China Extension - DBT Period: Placebon=33 Participants	0	-
China Extension - DBT Period: Gantenerumabn=35 Participants	1	-

Secondary/registry result

OLE Period: Number of Participants With at Least One ARIA-H MRI Finding

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - OLE Period: Placebo (DBT) to Gantenerumabn=9 Participants	1	-
Global - OLE Period: Gantenerumab (DBT) to Gantenerumabn=20 Participants	1	-

Secondary/registry result

OLE Period: Number of Participants With at Least One ARIA-E MRI Finding

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - OLE Period: Placebo (DBT) to Gantenerumabn=9 Participants	3	-
Global - OLE Period: Gantenerumab (DBT) to Gantenerumabn=20 Participants	2	-

Tau biomarkers

6 endpoints

Secondary/protocol endpoint

DBT Period: Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Total Tau (tTau)

Time frame:Baseline, Week 116

percent change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)

Time frame:Baseline, Week 116

percent change from baseline, improvement

Secondary/registry result

DBT Period: Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants

Time frame:Baseline, Week 116

change from baseline, improvement

Posted result

Group	Value (mean), SUVR	Standard error
Global - DBT Period: PlaceboROI: Temporal Composite Regionn=29 Participants	0.12	0.018
ROI: Medial Temporal Composite Region [not including the Hippocampus]n=29 Participants	0.08	0.014
ROI: Frontal Loben=29 Participants	0.08	0.012
ROI: Parietal Loben=29 Participants	0.09	0.020
Global - DBT Period: GantenerumabROI: Temporal Composite Regionn=48 Participants	0.13	0.014
ROI: Medial Temporal Composite Region [not including the Hippocampus]n=48 Participants	0.09	0.011
ROI: Frontal Loben=48 Participants	0.08	0.009
ROI: Parietal Loben=48 Participants	0.09	0.016

Difference in adjusted mean0.0195% CI-0.04 - 0.05p0.7816Mixed Model for Repeated Measures

Difference in adjusted means0.0195% CI-0.03 - 0.05p0.6203Mixed Model for Repeated Measures

Difference in adjusted means0.0095% CI-0.03 - 0.03p0.7754Mixed Model for Repeated Measures

Difference in adjusted means0.0095% CI-0.05 - 0.05p0.9022Mixed Model for Repeated Measures

Secondary/registry result

DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Total Tau (tTau)

Time frame:Baseline, Week 116

percent change from baseline, improvement

Posted result

Group	Value (geometric_mean), percent change in tTau	Reported bounds
Global - DBT Period: Placebon=84 Participants	3.2	--1.74 - 8.37
Global - DBT Period: Gantenerumabn=91 Participants	-16.6	--20.40 - -12.54

p<.001ANCOVA

Secondary/registry result

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)

Time frame:Baseline, Week 116

percent change from baseline, improvement

Posted result

Group	Value (geometric_mean), percent change in pTau-181	Reported bounds
Global - DBT Period: Placebon=84 Participants	1.1	--3.76 - 6.20
Global - DBT Period: Gantenerumabn=89 Participants	-25.2	--28.65 - -21.49

p<.001ANCOVA

Neurodegeneration biomarkers

4 endpoints

Secondary/protocol endpoint

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)

Time frame:Baseline, Week 116

Neurofilament light (NfL)

percent change from baseline, improvement

Secondary/protocol endpoint

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin

Time frame:Baseline, Week 116

percent change from baseline, improvement

Secondary/registry result

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)

Time frame:Baseline, Week 116

Neurofilament light (NfL)

percent change from baseline, improvement

Posted result

Group	Value (geometric_mean), percent change in NFL	Reported bounds
Global - DBT Period: Placebon=85 Participants	15.8	-9.67 - 22.32
Global - DBT Period: Gantenerumabn=93 Participants	12.1	-6.41 - 18.11

p0.396ANCOVA

Secondary/registry result

DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin

Time frame:Baseline, Week 116

percent change from baseline, improvement

Posted result

Group	Value (geometric_mean), percent change in neurogranin	Reported bounds
Global - DBT Period: Placebon=84 Participants	-0.6	--5.93 - 5.05
Global - DBT Period: Gantenerumabn=93 Participants	-22.3	--26.28 - -18.13

p<.001ANCOVA

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

DBT Period: Number of Participants With at Least One Adverse Event (AE)

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/registry result

DBT Period: Number of Participants With at Least One Adverse Event (AE)

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: Placebon=481 Participants	423	-
Global - DBT Period: Gantenerumabn=503 Participants	454	-

Other (unclassified)

12 endpoints

Secondary/protocol endpoint/low confidence

DBT Period: Number of Participants With Injection-Site Reactions

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/protocol endpoint/low confidence

DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Secondary/protocol endpoint/low confidence

China - DBT Period: Change From Baseline to Week 116 in VFT Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/protocol endpoint/low confidence

China - DBT Period: Number of Participants With at Least One AE

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Secondary/protocol endpoint/low confidence

China - DBT Period: Number of Participants With Injection-Site Reactions

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Secondary/protocol endpoint/low confidence

OLE Period: Number of Participants With at Least One AEs

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Secondary/registry result/low confidence

DBT Period: Number of Participants With Injection-Site Reactions

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: Placebon=481 Participants	43	-
Global - DBT Period: Gantenerumabn=503 Participants	94	-

Secondary/registry result/low confidence

DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - DBT Period: Gantenerumabn=489 Participants	10	-

Secondary/registry result/low confidence

China - DBT Period: Change From Baseline to Week 116 in VFT Score

Time frame:Baseline, Week 116

change from baseline, improvement

Secondary/registry result/low confidence

China - DBT Period: Number of Participants With at Least One AE

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
China Extension - DBT Period: Placebon=33 Participants	17	-
China Extension - DBT Period: Gantenerumabn=35 Participants	24	-

Secondary/registry result/low confidence

China - DBT Period: Number of Participants With Injection-Site Reactions

Time frame:From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
China Extension - DBT Period: Placebon=33 Participants	0	-
China Extension - DBT Period: Gantenerumabn=35 Participants	0	-

Secondary/registry result/low confidence

OLE Period: Number of Participants With at Least One AEs

Time frame:From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Global - OLE Period: Placebo (DBT) to Gantenerumabn=9 Participants	8	-
Global - OLE Period: Gantenerumab (DBT) to Gantenerumabn=20 Participants	16	-

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.