A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer’s Disease
- Conditions
- Alzheimer's Disease (AD)MedDRA version: 20.0Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-001184-25-ES
- Lead Sponsor
- Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1200
Main Study
? Participants who:
- Are age 60-80 years (inclusive) at the time of signing the ICF
- Cognitively unimpaired with a screening Clinical Dementia Rating Global Score (CDR-GS) of 0, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index (DMI) >=80
- Show evidence of cerebral amyloid accumulation
- Have an available person (referred to as a study partner” throughout the protocol) who: a) Has frequent and sufficient contact with the participant, and is willing and able to provide accurate information regarding the participant’s cognitive and functional abilities, signs the necessary ICF(s), and has sufficient cognitive capacity to accurately report on the participant’s cognitive and functional abilities; b) Is in sufficiently good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the duration of the study; c) Is fluent in the language of the tests used at the study site; d) Every effort should be made to have same study partner participate throughout the duration of the study
- Are fluent in the language of the tests used at the study site
- Have adequate visual and auditory acuity, sufficient to perform neuropsychological testing
- Have agreed not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study drug
- Have 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 during the treatment period and for at least 17 weeks after the final dose of study Treatment
Optional Blood-Based Biomarker Prescreening Procedure
? Participants who:
- Are age 60-80 years (inclusive) at the time of signing the Blood-Based Biomarker Prescreening Informed Consent Form (ICF)
- Do not have a known clinical diagnosis of cognitive impairment, MCI, prodromal AD, or any form of dementia
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900
Exclusions Related to central nervous system (CNS) Disorders
Participants who:
- Show any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD
- Have a clinical diagnosis of MCI, prodromal AD, or any form of dementia
- Have a history or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, intracerebral macrohemorrhage, or posterior reversible encephalopathy syndrome
- Have a history of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack or severe, clinically significant CNS trauma
- Have a history or presence of intracranial mass lesion that could potentially impair cognition or lead to progressive neurological deficits
- Have infections that may affect brain function or a history of infections that resulted in neurologic sequelae
- Have a history of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder
- Are at risk for suicide
- Have had history of alcohol and/or substance abuse or dependence
Exclusions Related to Imaging Findings
Participants who:
- According to the MRI central reader, show MRI evidence of any of the following:
* >1 lacunar infarcts
* Any territorial infarct >1 cm3
* Any white matter lesion that corresponds to an Overall
Fazekas score of 3
- Have a combined number of microbleeds and areas of leptomeningeal hemosiderosis on the MRI of >5
- Have a presence of any other significant cerebral abnormalities
- Are not able to tolerate MRI procedures or have a contraindication to MRI
Exclusions Related to Cardiovascular Disease
Participants who:
- Have a history or presence of clinically significant systemic vascular disease or atrial fibrillation
- Experienced unstable or clinically significant cardiovascular disease
- Have a history or presence of heart failure
- Have had uncontrolled hypertension
Exclusions Related to Hepatic and Renal Disorders
Participants who:
- Have chronic kidney disease or confirmed and unexplained impaired hepatic function
Exclusions Related to Infections and Immune Disorders
Participants who:
- Have a history of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection or spirochete infection of the CNS
- Have a history or presence of systemic autoimmune disorders
- Have systemic immunosuppression or immunomodulation
- Have current COVID-19 infection
Exclusions Related to Metabolic and Endocrine Disorders
Participants who:
- Have abnormal thyroid function
- Show evidence of folic acid deficiency or vitamin B-12 deficiency
- Have a screening hemoglobin A1c (HbA1c) >8% or poorly controlled insulin-dependent diabetes with hypoglycemic episodes
Exclusions Related to Medications
? Any previous administration of:
- Gantenerumab
- Active immunotherapy (vaccine) that is being evaluated to prevent or postpone cognitive decline
- Passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline
? Any other investigational treatment within 5 half-lives or 6 months
? Any previous administration of sodium oligomannate (GV-971)
? Any previous treatment with medications specifically intended to treat symptoms related to Parkinson’s disease or any other neurodegenerative disorder
? Anticonvulsant medications, typical and atypical anti-psychotic or neuroleptic medications, anticoagulation medications
? Psychedelic drugs and substa
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: ? To evaluate the efficacy of gantenerumab compared with control on cognition;Secondary Objective: ? To evaluate the efficacy of gantenerumab compared with control on clinical progression based on time from randomization to clinical progression to mild cognitive impairment (MCI) or dementia and time to onset of confirmed clinical progression<br>? To evaluate the efficacy of gantenerumab compared with control on cognition and/or function<br>? To evaluate the safety of gantenerumab compared with placebo<br>? To evaluate biomarkers of pharmacodynamics of gantenerumab compared with control;Primary end point(s): 1. Change from baseline to Year 4 in the Preclinical Alzheimer’s Cognitive Composite-5 (PACC-5) score;Timepoint(s) of evaluation of this end point: 1. Baseline to Year 4
- Secondary Outcome Measures
Name Time Method