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 1000 participants
Trial identifier NCT02051608, 2013-003390-95, WN28745

Summary

Part 1 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab in participants with mild Alzheimer disease. Participants 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. Part 2 is an open-label extension (OLE).

A positron emission tomography (PET) imaging substudy will be conducted within the main study. Eligible participants who provide separate informed consent will undergo 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 participants in each arm of the main study.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Primary purpose treatment
Masking participant, investigator
Arm
(Experimental)
Participants will receive either gantenerumab or placebo-matched to gantenerumab.
gantenerumab
Participants will receive gantenerumab as SC injection q4w up to Week 100
placebo
Participants will receive placebo as SC injection q4w up to Week 100q4w
(Experimental)
Participants will receive open label gantenerumab.
gantenerumab
Participants will receive gantenerumab as SC injection q4w up to Week 100
placebo
Participants will receive placebo as SC injection q4w up to Week 100q4w
(Experimental)
Participants will undergo PET imaging scans using the PET radioligand, a florbetapir F 18 injection.
florbetapir Amyvid
IV injection of florbetapir [Amyvid] up to 370 mega Becquerel (MBq) (10 millicurie [mCi]) of florbetapir and imaging for up to 15 minutes per PET scan conducted at screening and on 3 subsequent time points per protocol

Primary Outcomes

Measure
Mean Change From Baseline in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores at Week 104
time frame: Baseline, Week 104
Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104
time frame: Baseline, Week 104
Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs)
time frame: Baseline, Week 104

Secondary Outcomes

Measure
PET Imaging Substudy: Change From Baseline in Brain Amyloid Load Over Time Using Florbetapir
time frame: Baseline up to Week 104
Change From Baseline in Total Tau (t-tau) in CSF at Week 104
time frame: Baseline, Week 104
Change From Baseline in phosphorylated tau [p-tau]in CSF at Week 104
time frame: Baseline, Week 104
Change From Baseline in Abeta 1-42 levels in CSF at Week 104
time frame: Baseline, Week 104
Change From Baseline in Hippocampal Volume, as Assessed by Magnetic Resonance Image (MRI) at Week 104
time frame: Baseline, Week 104
Change From Baseline in Whole Brain Volume, as assessed by MRI at Week 104
time frame: Baseline, Week 104
Change From Baseline in Cortical thickness, as assessed by MRI at Week 104
time frame: Baseline, Week 104
Change From Baseline in Ventricular Volume, as Assessed by MRI at Week 104
time frame: Baseline, Week 104
Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104
time frame: Baseline, Week 104
Change From Baseline in CDR Sum of Boxes (SB) at Week 104
time frame: Baseline, Week 104
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104
time frame: Baseline, Week 104
Change From Baseline in NPI Domain Score at Week 104
time frame: Baseline, Week 104
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104
time frame: Baseline, Week 104
Safety: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
time frame: Baseline up to Week 152
Percentage of Participants with anti-gantenerumab antibodies
time frame: Baseline up to Week 152
Change From Baseline in Columbia - Suicide Severity Rating Scale (C-SSRS) Over Week 152
time frame: Baseline up to Week 152
Pharmacokinetics: Apparent Oral Clearance (CL/F) of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Pharmacokinetics: Apparent Volume of Distribution (V/F) of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Pharmacokinetics: Time to Reach Maximum Plasma Concentrations (Tmax) of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Pharmacokinetics: Minimum Observed Plasma Concentration (Cmin) of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Pharmacokinetics: Area Under Plasma Concentration (AUC) -Time Curve of gantenerumab
time frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152)
Quality of Life - Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104
time frame: Baseline, Week 104
Efficacy: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104
time frame: Baseline, Week 104
Efficacy: Change from Baseline in Dependence Scale (DS) at Week 104
time frame: Baseline, Week 104
Efficacy: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Life) Scale at Week 104
time frame: Baseline, Week 104
Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104
time frame: Baseline, Week 104
Time to Clinical Decline (as measured by Confirmed greater than of equal to [>=] 2-point decline on MMSE, Loss of >= 1 or 2 points on one or more ADL and I ADL, respectively)
time frame: Baseline up to Week 104
Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104
time frame: Baseline, Week 104

Eligibility Criteria

All participants from 50 years up to 90 years old.

Inclusion Criteria: - Clinical diagnosis of probable mild Alzheimer disease (AD) based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria or major NCD based whether or not receiving AD approved medication - Cerebral spinal fluid (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 participant, and is able to provide accurate information regarding the participant'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 PART 2 - All participants who have been randomized and are actively participating in the study are eligible for Part 2 Exclusion Criteria: - Dementia or neurocognitive disorder (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 Part 2 Participants who have been discontinued from the study

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; Part II: Open-Label Extension For Participating Patients
Trial information was received from ClinicalTrials.gov and was last updated in January 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.