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)

NCT ID: NCT05256134

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-19
• Study Completion Date: 2023-03-13

Brief Summary

A study to evaluate the efficacy and safety of gantenerumab in amyloid-positive, cognitively unimpaired participants at risk for or at the earliest stages of AD. The planned number of participants for this study is approximately 1200 participants randomized in a 1:1 ratio to receive either gantenerumab or placebo (600 participants randomized to gantenerumab and 600 participants randomized to placebo).

Conditions

Alzheimers Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Gantenerumab

Gantenerumab will be administered as subcutaneous (SC) injection with gradual uptitration.

Group Type: EXPERIMENTAL

Gantenerumab

Intervention Type: DRUG

Gantenerumab will be administered as per the dosing schedule described in the Arm description.

Placebo

Placebo will be administered as SC injection with gradual uptitration.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered as per the dosing schedule described in the Arm description.

Interventions

Gantenerumab

Gantenerumab will be administered as per the dosing schedule described in the Arm description.

Intervention Type: DRUG

Placebo

Placebo will be administered as per the dosing schedule described in the Arm description.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Banner Alzheimer?s Institute

Phoenix, Arizona, United States

Banner Sun Health Research Insitute

Sun City, Arizona, United States

Banner Alzheimer's Institute

Tucson, Arizona, United States

California Neuroscience Research Medical Group, Inc

Sherman Oaks, California, United States

JEM Research LLC

Atlantis, Florida, United States

Visionary Investigators Network - Neurology Aventura

Aventura, Florida, United States

Bradenton Research Center

Bradenton, Florida, United States

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Neuropsychiatric Research; Center of Southwest Florida

Fort Myers, Florida, United States

ClinCloud, LLC

Maitland, Florida, United States

K2 Medical Research, LLC

Maitland, Florida, United States

Optimus U Corp

Miami, Florida, United States

Renstar Medical Research

Ocala, Florida, United States

Charter Research - Winter Park/Orlando

Orlando, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

Alzheimer's Research and Treatment Center

Stuart, Florida, United States

Charter Research - Lady Lake/The Villages

The Villages, Florida, United States

Alzheimer?s Research and Treatment Center

Wellington, Florida, United States

Premiere Research Institute

West Palm Beach, Florida, United States

Center for Advanced Research & Education

Gainesville, Georgia, United States

Great Lakes Clinical Trials

Chicago, Illinois, United States

Via Christi Research

Wichita, Kansas, United States

Tandem Clinical Research, LLC

Marrero, Louisiana, United States

Quest Research Institute

Farmington Hills, Michigan, United States

University of Nebraska Medical Center; Dept of Neurological Sciences

Omaha, Nebraska, United States

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, United States

Velocity Clinical Research

East Syracuse, New York, United States

Alzheimer's Memory Center

Matthews, North Carolina, United States

Ohio State University; College of Medicine

Columbus, Ohio, United States

Senior Adults Specialty Research

Austin, Texas, United States

Kerwin Medical Center

Dallas, Texas, United States

Re:Cognition Health

Fairfax, Virginia, United States

Instituto Kremer

Córdoba, , Argentina

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales, Australia

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, Australia

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, Australia

Okanagan Clinical Trials

Kelowna, British Columbia, Canada

True North Clinical Research-Halifax

Halifax, Nova Scotia, Canada

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, Canada

Toronto Memory Program

Toronto, Ontario, Canada

Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica

Rome, Lazio, Italy

IRCCS Ospedale San Raffaele; U.O. di Neurologia

Milan, Lombardy, Italy

IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA

Pozzilli, Molise, Italy

AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica

Perugia, Umbria, Italy

KLIMED

Bia?ystok, , Poland

NZOZ Vitamed

Bydgoszcz, , Poland

NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

Późna, , Poland

Senior Sp. Z O.O. Poradnia Psychogeriatryczna

Sopot, , Poland

Centrum Medyczne Euromedis Sp. z o.o.

Szczecin, , Poland

NZOZ WCA

Wroc?aw, , Poland

Dong-A University Hospital

Busan, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Konkuk University Medical Center

Seoul, , South Korea

Hospital Quiron de Madrid; Servicio de Neurologia

Pozuelo de Alarcón, Madrid, Spain

BARCELONABETA BRAIN RESEARCH CENTER (BBRC); FUNDACIÓN PASQUAL MARAGALL, Servicio de Neurologia

Barcelona, , Spain

Fundación ACE; Servicio de Neurología

Barcelona, , Spain

Hospital Virgen del Rocío; Servicio de Neurología

Seville, , Spain

Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry

Mölndal, , Sweden

KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54

Stockholm, , Sweden

Re-Cognition

Birmingham, , United Kingdom

University of Exeter; College of Medicine and Health

Exeter, , United Kingdom

Panthera Biopartners Sheffield

Sheffield, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; Argentina; Australia; Canada; Italy; Poland; South Korea; Spain; Sweden; United Kingdom

References

Bauer A, Rabe C, Schiffman C, Rose F, Respondek G, Gullotta F, Schlieker L, Jethwa A, Schrurs I, Manuilova E, Ostrowitzki S, Bittner T. Blood-based pre-screening in the SKYLINE secondary prevention Ph3 gantenerumab study. Alzheimers Dement. 2025 Oct;21(10):e70676. doi: 10.1002/alz.70676.

Reference Type: DERIVED

PMID: 41085131 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021-001184-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WN42444

Identifier Type: -

Identifier Source: org_study_id