Prodromal Alzheimer’s Disease MedDRA version: 20.0 Level: LLT Classification code 10066571 Term: Progression of Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: GANTENERUMAB
Product Code: RO4909832/F08
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: gantenerumab
CAS Number: n/a
Current Sponsor code: RO4909832
Other de
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients, 50-85 years of age - Patients with prodromal Alzheimer's Disease who are not receiving memantine or cholinesterase inhibitors - Has a study partner who is able to provide accurate information as to the patient's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion - Has had sufficient education or work experience to exclude mental retardation - Study partner has noticed a recent gradual decrease in patient's memory (e.g. over the last 12 months), which the patient may or may not be aware of - Screening MMSE score of 24 or above 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 154 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 616
Exclusion criteria
Exclusion criteria: - Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning - A history of stroke - A documented history of transient ischemic attack within the last 12 months - History of schizophrenia, schizoaffective or bipolar disorder - Currently meets criteria for major depression - Within the last 2 years, unstable or clinical significant cardiovascular disease (e.g. myocardial infarction, angina pectoris) - Abnormal brain MRI scan Open label extension: - Prematurely discontinued from double-blind treatment for safety reasons affecting participation in the study - Abnormal brain MRI scan - Received another investigational medication after the end of doubleblind treatment - Participation deemed inappropriate by investigator or Sponsor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the effect of gantenerumab doses 105 mg and 225 mg given subcutaneous (SC) every 4 weeks (Q4W) vs. placebo on the change in the Clinical Dementia Rating scale Sum of Boxes (CDR-SOB), a global measure of cognition and functional ability. Dosing was stopped after a planned futility interim analysis that indicated low probability of meeting the primary outcome measure with the doses studied. Additional analyses suggested that higher doses of gantenerumab may have clinically relevant effects on cognition and function and are being tested in the open-label extension. Open-label extension (OLE): • To assess the short-term and long-term safety and tolerability of gantenerumab given at doses up to 1200 mg SC Q4W by magnetic resonance imaging (MRI), physical and neurological examinations, vital signs, blood safety tests, electrocardiogram (ECG)s, Columbia-Suicide Severity Rating Scale (C-SSRS), and adverse event monitoring ;Secondary Objective: • To evaluate the effect of gantenerumab vs. placebo - On cognition, on functioning and on onset of dementia - On the safety and tolerability of gantenerumab - On volumetric measures of the brain and structures - On change in cerebrospinal fluid biomarker measures (CSF) • Pharmacotkinetics • Antidrug antibodies (ADAs), and if relevant, evaluate its effect on the pharmacokinetic, pharmacodynamic, efficacy and safety parameters. Open-label extension • To evaluate the effect of 1200 mg gantenerumab SC Q4W over time compared to baseline and to start of open-label extension - On changes in amyloid load in the brain by PET using Florbetapir - 18F - On volumetric measures of the brain - On clinical outcomes (cognition and functioning) • To explore pharmacokinetics and ADAs with higher gantenerumab doses;Primary end point(s): 1. Change in CDR-SOB 2. Open-label extension: To assess long-term and short-term safety and tolerability of gantenerumab (nature and incidence of adverse events; MRI findings) ;Timepoint(s) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in cognition assessed with Alzheimer Disease Assessment Scale-Cognition , Mini Mental State Exam, Cambridge Neuropsychological Test Automated Battery (double-blind only), and Free and Cued Selective Reminding Test – Immediate Recall (double-blind only) 2. Change in functioning assessed with Functional Activities Questionnaire 3. Change in cerebrospinal fluid biomarker measures (T-tau, P-tau, and Abeta 1-42; double-blind only) 4. Change in brain amyloid load using PET Positron Emission Tomography 5. Pharmacokinetics: gantenerumab levels 6. Safety (nature and incidence of adverse events; MRI findings) ;Timepoint(s) of evaluation of this end point: 1-6. double-blind, 2 years; open-label extension, 3 years | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, Turkey, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed