Clinical trial NCT05256134: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Alzheimers Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-02-25
Enrollment: 25
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Key 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.

Primary outcomes:
measure: Change From Baseline in PACC-5 Score
timeFrame: Baseline to early termination visit (up to 225 days from start of treatment)
Secondary outcomes:
measure: Time From Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia Due to AD
timeFrame: Randomization to early termination Visit (up to 225 days from start of treatment)
measure: Time to Onset of Confirmed Clinical Progression
timeFrame: Randomization to early termination Visit (up to 225 days from start of treatment)
measure: Change From Baseline in the Amsterdam Instrumental Activities of Daily Living Questionnaire Short Version (A-IADL-Q-SV)
timeFrame: Baseline to early termination visit (up to 225 days from start of treatment)
measure: Change From Baseline in the Cognitive Function Instrument Acute (CFIa) Participant Version
timeFrame: Baseline to early termination visit (up to 225 days from start of treatment)
measure: Change From Baseline in the CFIa Study Partner Version
timeFrame: Baseline to early termination visit (up to 225 days from start of treatment)
measure: Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
timeFrame: Baseline to early termination visit (up to 225 days from start of treatment)
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
timeFrame: Day 1 to safety follow-up visit (up to 310 days from start of treatment)
measure: Number of Participants With Anti-Drug Antibodies (ADAs) to Gantenerumab
timeFrame: Day 1 to early termination visit (up to 216 days from start of treatment)
measure: Number of Participants With Magnetic Resonance Imaging (MRI) Findings: Amyloid-related Imaging Abnormalities - Edema/Effusion (ARIA-E) and ARIA-Hemosiderin Deposition (ARIA-H)
timeFrame: Day 1 to early termination visit (up to 248 days from start of treatment)
measure: Number of Participants With Injection-site Reactions (ISRs)
timeFrame: Day 1 to safety follow-up visit (up to 310 days from start of treatment)
measure: Number of Participants With Post-baseline Suicidal Behaviors and Ideations as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Day 1 to safety follow-up visit (up to 310 days from start of treatment)
measure: Change in Brain Amyloid Load Over Time as Measured by Amyloid Positron Emission Tomography (PET) in a Subset of Participants
timeFrame: Baseline
measure: Change in Brain Tau Load Over Time as Measured by Tau PET in a Subset of Participants
timeFrame: Baseline
measure: Change in Cerebrospinal Fluid (CSF) Amyloid (A) Peptide Beta (β): Aβ 1-42 Over Time in a Subset of Participants
timeFrame: Baseline
measure: Change in CSF Amyloid Peptide: Aβ 1-40 Over Time in a Subset of Participants
timeFrame: Baseline
measure: Change in CSF Neurofilament Light (NFL) Over Time in a Subset of Participants
timeFrame: Baseline
measure: Change in CSF Phosphorylated Tau (pTau) Over Time in a Subset of Participants
timeFrame: Baseline
measure: Change in CSF Total Tau (tTau) Over Time in a Subset of Participants
timeFrame: Baseline
measure: Change in Whole Brain Volume Over Time as Determined by MRI in a Subset of Participants
timeFrame: Baseline
measure: Change in Total Ventricular Volume Over Time as Determined by MRI in a Subset of Participants
timeFrame: Baseline
measure: Change in Hippocampal Volume Over Time as Determined by MRI in a Subset of Participants
timeFrame: Baseline
Other outcomes:
measure: Change in Blood Aβ 1-42 Over Time in All Participants
timeFrame: Baseline to safety follow-up visit (up to 310 days from start of treatment)
measure: Change in Blood Aβ 1-40 Over Time in All Participants
timeFrame: Baseline to safety follow-up visit (up to 310 days from start of treatment)
measure: Change in Blood NFL Over Time in All Participants
timeFrame: Baseline to safety follow-up visit (up to 310 days from start of treatment)
measure: Change in Blood pTau Over Time in All Participants
timeFrame: Baseline to safety follow-up visit (up to 310 days from start of treatment)
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer?s Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Insitute
state: Arizona
city: Tucson
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc
state: California
city: Atlantis
country: United States
facility: JEM Research LLC
state: Florida
city: Aventura
country: United States
facility: Visionary Investigators Network - Neurology Aventura
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research; Center of Southwest Florida
state: Florida
city: Maitland
country: United States
facility: ClinCloud, LLC
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research, LLC
state: Florida
city: Miami
country: United States
facility: Optimus U Corp
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park/Orlando
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Stuart
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: The Villages
country: United States
facility: Charter Research - Lady Lake/The Villages
state: Florida
city: Wellington
country: United States
facility: Alzheimer?s Research and Treatment Center
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Gainesville
country: United States
facility: Center for Advanced Research & Education
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Wichita
country: United States
facility: Via Christi Research
state: Kansas
city: Marrero
country: United States
facility: Tandem Clinical Research, LLC
state: Louisiana
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center; Dept of Neurological Sciences
state: Nebraska
city: Springfield
country: United States
facility: The Cognitive and Research Center of New Jersey
state: New Jersey
city: East Syracuse
country: United States
facility: Velocity Clinical Research
state: New York
city: Matthews
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University; College of Medicine
state: Ohio
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Fairfax
country: United States
facility: Re:Cognition Health
state: Virginia
city: Córdoba
country: Argentina
facility: Instituto Kremer
city: Macquarie Park
country: Australia
facility: KaRa Institute of Neurological Diseases
state: New South Wales
city: Heidelberg West
country: Australia
facility: Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
state: Victoria
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Foundation
state: Western Australia
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research-Halifax
state: Nova Scotia
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Roma
country: Italy
facility: Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica
state: Lazio
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele; U.O. di Neurologia
state: Lombardia
city: Pozzilli
country: Italy
facility: IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
state: Molise
city: Perugia
country: Italy
facility: AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica
state: Umbria
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Bia?ystok
country: Poland
facility: KLIMED
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Pozna?
country: Poland
facility: NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
city: Sopot
country: Poland
facility: Senior Sp. Z O.O. Poradnia Psychogeriatryczna
city: Szczecin
country: Poland
facility: Centrum Medyczne Euromedis Sp. z o.o.
city: Wroc?aw
country: Poland
facility: NZOZ WCA
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid; Servicio de Neurologia
state: Madrid
city: Barcelona
country: Spain
facility: BARCELONABETA BRAIN RESEARCH CENTER (BBRC); FUNDACIÓN PASQUAL MARAGALL, Servicio de Neurologia
city: Barcelona
country: Spain
facility: Fundación ACE; Servicio de Neurología
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío; Servicio de Neurología
city: Mölndal
country: Sweden
facility: Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
city: Stockholm
country: Sweden
facility: KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
city: Birmingham
country: United Kingdom
facility: Re-Cognition
city: Exeter
country: United Kingdom
facility: University of Exeter; College of Medicine and Health
city: Sheffield
country: United Kingdom
facility: Panthera Biopartners Sheffield
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: