SKYLINE

TerminatedPhase 3Results posted

A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease (AD)

A Phase III, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease

Lead sponsor

Hoffmann-La Roche

Asset

Gantenerumab

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criterion

•Study partner/caregiver required

Primary endpoint

•Mini-Mental State Examination (MMSE)

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 number2021-001184-25

NCT IDNCT05256134

Org study IDWN42444

Timeline

Milestones

Study first posted2022-02-25actual

Study start2022-04-19actual

Primary completion2023-03-13actual

Study completion2023-03-13actual

Results first posted2024-07-09actual

Last update posted2025-06-12actual

Assets

Drug assets

Gantenerumab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Key Inclusion Criteria:

•Willing and able to comply with the study protocol and complete all aspects of the study [including cognitive and functional assessments, physical and neurological examinations, MRI, CSF collection, genotyping, and positron emission tomography (PET) imaging].

•Cognitively unimpaired with a screening clinical dementia rating global score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) >=80.

•Evidence of cerebral amyloid accumulation.

•Participants who have an available person (referred to as a "study partner").

•Fluent in the language of the tests used at the study site.

•Adequate visual and auditory acuity, sufficient to perform neuropsychological testing (eye glasses and hearing aids are permitted).

•Agreed not to participate in other interventional research studies for the duration of this trial.

•For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 17 weeks after the final dose of study treatment

Exclusion criteria

•Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD.

•Clinical diagnosis of mild cognitive impairment (MCI), prodromal AD, or any form of dementia.

•History or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage.

•History or presence of posterior reversible encephalopathy syndrome.

•History of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening.

•History of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) central nervous system (CNS) trauma (e.g., cerebral contusion).

•History or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits.

•Infections that may affect brain function or a history of infections that resulted in neurologic sequelae [e.g., human immunodeficiency virus (HIV), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis].

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

•At risk for suicide.

•History of alcohol and/or substance abuse or dependence.

•History or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure.

•Within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction).

•Uncontrolled hypertension.

•Chronic kidney disease, indicated by creatinine clearance <30 mL/min.

•Confirmed and unexplained impaired hepatic function.

•History of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection that has not been adequately treated.

•History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.

•Systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications.

•Current COVID-19 infection.

•Evidence of folic acid or vitamin B-12 deficiency.

•Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening.

•Any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening.

•Typical/Atypical anti-psychotic medications or neuroleptic medications.

•Anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization.

•Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists are exclusionary at screening.

•Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab.

•Impaired coagulation.

•Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients.

•Participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility.

•Participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.

Endpoints (52)

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

Tau biomarkers

Neuroimaging

Memory

Neurodegeneration biomarkers

Other (unclassified)

Behavior / neuropsychiatric

Disease progression

Safety / tolerability / PK

Global cognition

8 endpoints

Primary/protocol endpoint

Change From Baseline in PACC-5 Score

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

Change From Baseline in PACC-5 Score

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=12 Participants	-0.052	0.5790
Gantenerumabn=13 Participants	-0.119	0.6038

Secondary/protocol endpoint

Time to Onset of Confirmed Clinical Progression

Time frame:Randomization to early termination Visit (up to 225 days from start of treatment)

time to event, event

Secondary/protocol endpoint

Change From Baseline in the Cognitive Function Instrument Acute (CFIa) Participant Version

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

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

change from baseline, improvement

Secondary/registry result

Time to Onset of Confirmed Clinical Progression

Time frame:Randomization to early termination Visit (up to 225 days from start of treatment)

time to event, event

Posted result

Group	Value (median), weeks	Reported bounds
Placebon=12 Participants	NA	-NA - NA
Gantenerumabn=13 Participants	NA	-NA - NA

Secondary/registry result

Change From Baseline in the Cognitive Function Instrument Acute (CFIa) Participant Version

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=12 Participants	0.3	4.52
Gantenerumabn=11 Participants	0.9	4.70

Secondary/registry result

Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

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

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=12 Participants	0.29	0.498
Gantenerumabn=10 Participants	-0.05	0.158

Memory

4 endpoints

Secondary/protocol endpoint

Change From Baseline in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in the CFIa Study Partner Version

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Secondary/registry result

Change From Baseline in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=12 Participants	-1.3	3.93
Gantenerumabn=11 Participants	-0.4	1.29

Secondary/registry result

Change From Baseline in the CFIa Study Partner Version

Time frame:Baseline to early termination visit (up to 225 days from start of treatment)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=12 Participants	-0.8	3.24
Gantenerumabn=10 Participants	0.2	5.14

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Number of Participants With Post-baseline Suicidal Behaviors and Ideations as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Secondary/registry result

Number of Participants With Post-baseline Suicidal Behaviors and Ideations as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebon=12 Participants	1	-
Gantenerumabn=11 Participants	0	-

Disease progression

2 endpoints

Secondary/protocol endpoint

Time From Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia Due to AD

Time frame:Randomization to early termination Visit (up to 225 days from start of treatment)

categorical status, descriptive

Secondary/registry result

Time From Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia Due to AD

Time frame:Randomization to early termination Visit (up to 225 days from start of treatment)

categorical status, descriptive

Posted result

Group	Value (median), weeks	Reported bounds
Placebon=12 Participants	NA	-NA - NA
Gantenerumabn=13 Participants	NA	-NA - NA

Amyloid biomarkers

12 endpoints

Secondary/protocol endpoint

Number of Participants With Magnetic Resonance Imaging (MRI) Findings: Amyloid-related Imaging Abnormalities - Edema/Effusion (ARIA-E) and ARIA-Hemosiderin Deposition (ARIA-H)

Time frame:Day 1 to early termination visit (up to 248 days from start of treatment)

event count, event

Secondary/protocol endpoint

Change in Brain Amyloid Load Over Time as Measured by Amyloid Positron Emission Tomography (PET) in a Subset of Participants

Time frame:Baseline

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Amyloid (A) Peptide Beta (β): Aβ 1-42 Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/protocol endpoint

Change in CSF Amyloid Peptide: Aβ 1-40 Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Number of Participants With Magnetic Resonance Imaging (MRI) Findings: Amyloid-related Imaging Abnormalities - Edema/Effusion (ARIA-E) and ARIA-Hemosiderin Deposition (ARIA-H)

Time frame:Day 1 to early termination visit (up to 248 days from start of treatment)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboARIA-En=12 Participants	0	-
ARIA-Hn=12 Participants	0	-
GantenerumabARIA-En=13 Participants	0	-
ARIA-Hn=13 Participants	1	-

Secondary/registry result

Change in Brain Amyloid Load Over Time as Measured by Amyloid Positron Emission Tomography (PET) in a Subset of Participants

Time frame:Baseline

Amyloid PET Centiloid

change from baseline, improvement

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Amyloid (A) Peptide Beta (β): Aβ 1-42 Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in CSF Amyloid Peptide: Aβ 1-40 Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Other/protocol endpoint

Change in Blood Aβ 1-42 Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Other/protocol endpoint

Change in Blood Aβ 1-40 Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Other_pre_specified/registry result

Change in Blood Aβ 1-42 Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Other_pre_specified/registry result

Change in Blood Aβ 1-40 Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Tau biomarkers

8 endpoints

Secondary/protocol endpoint

Change in Brain Tau Load Over Time as Measured by Tau PET in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/protocol endpoint

Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/protocol endpoint

Change in CSF Total Tau (tTau) Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in Brain Tau Load Over Time as Measured by Tau PET in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in CSF Total Tau (tTau) Over Time in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Other/protocol endpoint

Change in Blood pTau Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Other_pre_specified/registry result

Change in Blood pTau Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

change from baseline, improvement

Neurodegeneration biomarkers

4 endpoints

Secondary/protocol endpoint

Change in CSF Neurofilament Light (NFL) Over Time in a Subset of Participants

Time frame:Baseline

Neurofilament light (NfL)

change from baseline, improvement

Secondary/registry result

Change in CSF Neurofilament Light (NFL) Over Time in a Subset of Participants

Time frame:Baseline

Neurofilament light (NfL)

change from baseline, improvement

Other/protocol endpoint

Change in Blood NFL Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

Neurofilament light (NfL)

change from baseline, improvement

Other_pre_specified/registry result

Change in Blood NFL Over Time in All Participants

Time frame:Baseline to safety follow-up visit (up to 310 days from start of treatment)

Neurofilament light (NfL)

change from baseline, improvement

Neuroimaging

6 endpoints

Secondary/protocol endpoint

Change in Whole Brain Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/protocol endpoint

Change in Total Ventricular Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/protocol endpoint

Change in Hippocampal Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in Whole Brain Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in Total Ventricular Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Secondary/registry result

Change in Hippocampal Volume Over Time as Determined by MRI in a Subset of Participants

Time frame:Baseline

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Secondary/registry result

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboAEsn=12 Participants	6	-
SAEsn=12 Participants	0	-
AESIsn=12 Participants	0	-
GantenerumabAEsn=13 Participants	5	-
SAEsn=13 Participants	0	-
AESIsn=13 Participants	0	-

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Number of Participants With Anti-Drug Antibodies (ADAs) to Gantenerumab

Time frame:Day 1 to early termination visit (up to 216 days from start of treatment)

event count, event

Secondary/protocol endpoint/low confidence

Number of Participants With Injection-site Reactions (ISRs)

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Secondary/registry result/low confidence

Number of Participants With Anti-Drug Antibodies (ADAs) to Gantenerumab

Time frame:Day 1 to early termination visit (up to 216 days from start of treatment)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Gantenerumabn=13 Participants	0	-

Secondary/registry result/low confidence

Number of Participants With Injection-site Reactions (ISRs)

Time frame:Day 1 to safety follow-up visit (up to 310 days from start of treatment)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebon=12 Participants	0	-
Gantenerumabn=13 Participants	1	-

Publications (2)

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.