Overview

This trial is active, not recruiting.

Condition alzheimer's disease
Treatments florbetapir, gantenerumab, placebo
Phase phase 3
Sponsor Hoffmann-La Roche
Start date March 2014
End date July 2018
Trial size 389 participants
Trial identifier NCT02051608, 2013-003390-95, WN28745

Summary

This multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab in patients with mild Alzheimer disease. Patients will be randomized to receive either gantenerumab subcutaneously every 4 weeks or placebo subcutaneously every 4 weeks. Approved Alzheimer medication is allowed if on stable dose for 3 months prior to screening.

A positron emission tomography (PET) imaging substudy will be conducted within the main study. Eligible patients who provide separate informed consent will undergo up to four PET imaging scans using the radioligand florbetapir as a pharmacodynamic measure of changes in brain amyloid load over time. The substudy's target sample size is 100 patients in each arm of the main study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double-blind
Primary purpose treatment
Arm
(Experimental)
gantenerumab
SC q4w up to Week 100
(Experimental)
florbetapir Amyvid
intravenous injection of florbetapir [Amyvid™] up to 370 MBq (10 mCi) of florbetapir and imaging for up to 15 minutes per PET scan conducted at screening and on 3 subsequent timepoints per protocol
(Placebo Comparator)
placebo
SC q4w

Primary Outcomes

Measure
PET imaging substudy: Change in brain amyloid load over time using florbetapir
time frame: from baseline to Week 104
Mean change in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores
time frame: from baseline to Week 104
Mean change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores
time frame: from baseline to Week 104

Secondary Outcomes

Measure
Change in biomarkers (t-tau, p-tau, Abeta 1-42 levels) in cerebral spinal fluid
time frame: from baseline to Week 104
Change in MRI volumetry, assessed on structural MRI
time frame: from baseline to Week 104
Change in Clinical Dementia Rating (CDR-SB/CDR-GS)
time frame: from baseline to Week 104
Change in neuropsychiatric behavior: Neuropsychiatric Inventory (NPI) total and domain scores
time frame: from baseline to Week 104
Change in cognition: MMSE total score
time frame: from baseline to Week 104
Safety: Incidence of adverse events, serious adverse events and treatment discontinuations
time frame: 152 weeks
Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB)
time frame: from baseline to Week 104

Eligibility Criteria

Male or female participants from 50 years up to 90 years old.

Inclusion Criteria: - Adult patients, 50 to 90 years of age, inclusive - Clinical diagnosis of probable mild Alzheimer disease (AD) based on NINCDS/ADRDA criteria whether or not receiving AD approved medication - CSF result consistent with the presence of amyloid pathology - Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient contact with the patient, and is able to provide accurate information regarding the patient's cognitive and functional abilities - Fluency in the language of the tests used at the study site - Willingness and ability to complete all aspects of the study - Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted) - If currently receiving approved medications for AD, the dosing regimen must have been stable for 3 months prior to screening - Agreement not to participate in other research studies for the duration of this trial and its associated substudies Exclusion Criteria: - Dementia or NCD due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia - History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function - History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months - History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits - History of schizophrenia, schizoaffective disorder, or bipolar disorder - Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years (nicotine use is allowed) - History or presence of atrial fibrillation - Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher) - Uncontrolled hypertension - Chronic kidney disease - Impaired hepatic function PET imaging substudy, in addition to above: - Prior participation in other research study or clinical care within the last year such that the total radiation exposure would exceed the local or national annual limits

Additional Information

Official title A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER, EFFICACY AND SAFETY STUDY OF GANTENERUMAB IN PATIENTS WITH MILD ALZHEIMER'S DISEASE
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.