A Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer’s Disease

Phase 1

Conditions: Alzheimer's Disease (AD)
MedDRA version: 20.0Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0Level: PTClassification code 10074616Term: Prodromal Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-001384-87-DE

Lead Sponsor: 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: 192

Inclusion Criteria

• Age 50-90 years old
• Probable AD dementia or prodromal AD
• Availability of a reliable study partner who accepts to participate in study procedure throughout the study duration
• Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory
• Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination score >= 22 and Clinical Dementia Rating global score of 0.5 or 1.0, as well as a clinical dementia rating memory domain score >= 0.5
• If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment
• Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche sponsored non-interventional
studies
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug
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 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 151

Exclusion Criteria

• Any evidence of a condition other than AD that may affect cognition
• History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
• Uncontrolled hypertension
• Unstable or clinically significant cardiovascular, kidney or liver disease
• History or presence of clinically evident cerebrovascular disease, posterior reversible encephalopathy syndrome, any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent, in the opinion of the investigator, with a transient ischemic attack
• History of severe, clinically significant CNS trauma, history or presence of intracranial mass that could potentially impair cognition
• Any contraindications to brain magnetic resonance imaging
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
• History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
• History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
• At risk for suicide in the opinion of the investigator
• Alcohol and/or substance abuse or dependence within the past 2 years

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 pharmacodynamic (PD) effect of a once a week (Q1W) dosing regimen of gantenerumab on brain amyloid load as determined by positron emission tomography (PET) imaging in participants with early (prodromal to mild) AD;Secondary Objective: • To evaluate caregiver overall satisfaction and confidence<br>• To assess the safety of gantenerumab in participants with early (prodromal to mild) AD<br>• To characterize the pharmacokinetic profile of gantenerumab using a new titration scheme and especially at the Q1W dosing frequency<br>• To assess the PD effect of the dosing frequency on brain amyloid;Primary end point(s): The change from baseline to Week 104 in deposited amyloid as measured by brain amyloid PET Centiloid levels;Timepoint(s) of evaluation of this end point: From baseline (screening amyloid PET) to Week 104

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Responses to Caregiver questionnaire up to Week 104<br>2. Nature, frequency, severity, and timing of adverse events and serious adverse events<br>3. Physical examinations, vital signs, blood tests, ECGs, and Columbia?Suicide Severity Rating Scale<br>4. Nature, frequency, severity, and timing of MRI findings: amyloid-related imaging abnormalities-edema/effusion; amyloid-related imaging abnormalities-hemosiderin deposition<br>5. Nature, frequency, severity, and timing of injection site reactions<br>6. Presence of anti-drug antibody (ADAs) during the study relative to the presence of ADAs at baseline<br>7. Plasma concentration of gantenerumab at specified timepoints<br>8.The influence of dosing frequency information on the performance of a quantitative PK-PD model developed based on PK and PET from this and previous studies<br>;Timepoint(s) of evaluation of this end point: 1. Up to Week 104<br>2-7. Baseline up to end of study (Week 120)<br>8. At Week 104

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