Phase 3
N=387
A Study of Gantenerumab in Participants With Mild Alzheimer Disease
Alzheimer's Disease
Bottom Line
View on ClinicalTrials.gov: NCT02051608 ↗Enrolled (actual)
387
Serious AEs
30.1%
Results posted
Jun 2022
Primary outcome: Primary: Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) — 91.5; 95.4; 24.8; 38.0 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo (Drug); Gantenerumab (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) |
91.5; 95.4; 24.8; 38.0 | — |
| PRIMARY Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) |
2.6; 2.8 | — |
| PRIMARY Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment |
12.0; 15.7 | — |
| SECONDARY Part 1: Percentage of Participants With AEs, SAEs |
80.5; 82.8; 12.3; 12.0 | — |
| SECONDARY Part 1: Percentage of Participants With Treatment Emergent ADAs |
3.6; 11.5 | — |
| SECONDARY Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints |
4.11; 2.06; 3.11; 3.35; 3.71; 7.61 | — |
| SECONDARY Part 1: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment |
2.6; 6.8 | — |
| SECONDARY Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104 |
-11.24; -12.10; -12.49; -11.34 | — |
| SECONDARY Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104 |
-4.89; -4.91 | — |
| SECONDARY Part 2: Percent Change From Baseline in Cortical Thickness at Week 104 |
-5.84; -5.58 | — |
| SECONDARY Part 2: Ventricular Volume as Measured by MRI at Week 104 |
86.70; 86.21 | — |
| SECONDARY Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints |
80.6; 89.1; 43.5; 3.66; 45.2; 55.8 | — |
| SECONDARY Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants |
-81.01; -84.93 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02051608). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.