A Study of Gantenerumab in Participants With Mild Alzheimer Disease

Roche

Status and phase: Completed; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: Placebo; Drug: Gantenerumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02051608

2013-003390-95 (EudraCT Number)

WN28745

Details and patient eligibility

About

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.

Enrollment: 389 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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389 participants in 4 patient groups, including a placebo group

Part 1 (Double Blind treatment): Placebo

Placebo Comparator group

Description:

Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study.

Treatment:

Drug: Placebo

Part 1 (Double Blind treatment): Gantenerumab

Experimental group

Description:

Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.

Treatment:

Drug: Gantenerumab

Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg

Placebo Comparator group

Description:

Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.

Treatment:

Drug: Placebo

Part 2 (OLE treatment): Gantenerumab up to 1200 mg

Experimental group

Description:

Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.

Treatment:

Drug: Gantenerumab