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)

JRCT ID: jRCT2031220468

Registered date:28/11/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Preclinical AD
• Date of first enrollment: 30/01/2023
• Target sample size: 24
• Countries of recruitment: Argentina,Japan,Australia,Japan,Canada,Japan,Italy,Japan,Korea,Japan,Poland,Japan,Spain,Japan,Sweden,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

Primary Outcome

Efficacy
Change from Baseline to Year 4 in Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) Score

Secondary Outcome

Safety, Efficacy, Phamacokinetics, Phamacodynamics, Other
1. Time from Randomization to Clinical Progression to Mild Cognitive Impairment (MCI) or Dementia due to AD
2. Time to Onset of Confirmed Clinical Progression
3. Change from Baseline to Year 4 in the A-IADL-Q-SV, CFIa, CDR-SB
4. Number of Participants with AEs, SAEs and AESIs
5. Number of Participants with Anti-Drug Antibodies (ADAs)
6. Change in Brain Amyloid, Tau Load Over Time in a Subset of Partcipants
7. Change in Cerebrospinal Fluid (CSF) Abeta 1-42, 1-40, NfL, pTau, tTau Over Time in a Subset of Participants
8. Change in Blood Abeta 1-42, 1-40, NfL, pTau Over Time
9. Change in Whole Brain, Ventricle, Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)

Key inclusion & exclusion criteria

• Age minimum: >= 60age old
• Age maximum: <= 80age old
• Gender: Both

Include 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.

Exclude 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 of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder.
- History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.
- 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.

Related Information

• Primary Sponsor: Gesine Respondek, M.D.
• Secondary ID(s): NCT05256134