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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02051608




Registration number
NCT02051608
Ethics application status
Date submitted
30/01/2014
Date registered
31/01/2014
Date last updated
10/02/2023

Titles & IDs
Public title
A Study of Gantenerumab in Participants With Mild Alzheimer Disease
Scientific 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
Secondary ID [1] 0 0
2013-003390-95
Secondary ID [2] 0 0
WN28745
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Gantenerumab

Placebo comparator: Part 1 (Double Blind treatment): Placebo - Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study.

Experimental: Part 1 (Double Blind treatment): Gantenerumab - 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.

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

Experimental: Part 2 (OLE treatment): Gantenerumab up to 1200 mg - 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: Drugs: Placebo
Participants received Placebo SC injection Q4W.

Treatment: Drugs: Gantenerumab
Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Timepoint [1] 0 0
First dose up to 4 weeks after the last dose of study drug (up to 249 weeks)
Primary outcome [2] 0 0
Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)
Timepoint [2] 0 0
First dose up to last dose (Baseline up to until maximum 5 years)
Primary outcome [3] 0 0
Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment
Timepoint [3] 0 0
First dose up to 4 weeks after the last dose in OLE (Up to approximately 249 weeks)
Secondary outcome [1] 0 0
Part 1: Percentage of Participants With AEs, SAEs
Timepoint [1] 0 0
First dose up to last dose (Up to approximately 152 weeks)
Secondary outcome [2] 0 0
Part 1: Percentage of Participants With Treatment Emergent ADAs
Timepoint [2] 0 0
First dose up to last dose (Up to approximately 152 weeks)
Secondary outcome [3] 0 0
Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints
Timepoint [3] 0 0
Pre-dose: Weeks 4, 8, 12, 24, 48, 72 and Post dose: Day 4
Secondary outcome [4] 0 0
Part 1: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment
Timepoint [4] 0 0
First dose up to last dose (Up to approximately 152 weeks)
Secondary outcome [5] 0 0
Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104
Timepoint [5] 0 0
Baseline (Part 1 screening), Week 104
Secondary outcome [6] 0 0
Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104
Timepoint [6] 0 0
Baseline (Part 1 screening), Week 104
Secondary outcome [7] 0 0
Part 2: Percent Change From Baseline in Cortical Thickness at Week 104
Timepoint [7] 0 0
Baseline (Part 1 screening), Week 104
Secondary outcome [8] 0 0
Part 2: Ventricular Volume as Measured by MRI at Week 104
Timepoint [8] 0 0
Part 2: Week 104
Secondary outcome [9] 0 0
Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints
Timepoint [9] 0 0
Pre-dose: Weeks 104, 116, 156, 208; Post-dose: Weeks 53, 101
Secondary outcome [10] 0 0
Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants
Timepoint [10] 0 0
Baseline, Week 156

Eligibility
Key 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
Minimum age
50 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/04/2021
Sample size
Target
Accrual to date
Final
389
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital; Memory Trials Centre - Adelaide
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment hospital [3] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [4] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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California
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Florida
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Indiana
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Louisiana
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Michigan
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Missouri
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New Jersey
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New York
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North Carolina
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Oklahoma
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Pennsylvania
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Rhode Island
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Tennessee
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Texas
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Utah
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Argentina
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Bruxelles
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Leuven
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Manchester
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Preston
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02051608