A Study of Gantenerumab in Patients with Mild Alzheimer Disease

• Register: EUCTR
• Last refreshed on: 17 August 2021
• Main ID: EUCTR2013-003390-95-IT
• Date of registration: 08/01/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study of Gantenerumab in Patients 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 - MARGUERITE ROAD
• Date of first enrolment: 27/02/2014
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003390-95
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Guatemala, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Adult patients, 50 to 90 years of age, inclusive
- Clinical diagnosis of probable mild Alzheimer disease based on NINCDS/ADRDA criteria
- 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, doses must have been stable for at least 5 months prior to randomization
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900

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 abuse or dependence (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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

MILD ALZHEIMER’S DISEASE
MedDRA version: 16.1 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Gantenerumab
Product Code: Ro 490-9832/F12
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: gantenerumab
CAS Number: n/a
Current Sponsor code: RO4909832
Other descriptive name: human anti-Aß antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 105-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Gantenerumab
Product Code: Ro 490-9832/F14
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: gantenerumab
CAS Number: n/a
Current Sponsor code: RO4909832
Other descriptive name: human anti-Aß antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 225-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: to evaluate the efficacy of gantenerumab compared with placebo administered to patients by SC injection over 100 weeks as measured by the following co-primary endpoints (final outcome assessment 4 weeks after the final dose):
• Cognition measured by the Alzheimer’s Disease Activity Scale-Cognitive (ADAS-Cog) (13-item)
• Function assessed by the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

Secondary Objective: 1. to evaluate the benefits of gantenerumab versus placebo administered to patients by SC injection over 100 weeks on slowing clinical decline and disease progression by assessing the following:
• Time to clinically evident decline
• Disease pathology biomarkers
2. Additional secondary endpoints
· Global: Effect on severity of dementia and global measures of cognition and function
· Cognition: Effect on cognition
· Behavioar: Effect on behavioral and neuropsychological symptoms of AD
· Other AD symptoms and effects: Effect of gantenerumab on health-related QoL, patient-individualized goal achievement (sites in English- and French-speaking countries only), on caregiver emotional well-being, on the amount of assistance patients with dementia require in performing daily activities

Timepoint(s) of evaluation of this end point: - from baseline to Week 104

Primary end point(s): Mean change in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores

Mean change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores

Secondary Outcome(s)

Secondary end point(s): - Change in biomarkers (t-tau, p-tau, Abeta 1-42 levels) in cerebral spinal fluid
- Change in MRI volumetry, assessed on structural MRI
- Change in Clinical Dementia Rating (CDR-SB/CDR-GS)
- Change in neuropsychiatric behaviour: Neuropsychiatric Inventory (NPI) total and domain scores
- Change in cognition: MMSE total score
- Safety: Incidence of adverse events, serious adverse events and treatment discontinuations

Timepoint(s) of evaluation of this end point: - from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- from baseline to Week 104
- 152 weeks

Secondary ID(s)

2013-003390-95-GB

WN28745

Source(s) of Monetary Support

F.Hoffmann-La Roche Ltd.

Ethics review

Status: Approved
Approval date: 27/02/2014
Contact: