MILD ALZHEIMER’S DISEASE MedDRA version: 20.0 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 - Adult patients, 50 to 90 years of age, inclusive - Clinical diagnosis of probable mild Alzheimer disease based on NINCDS/ADRDA criteria or major NCD due to AD of mild severity, whether or not receiving AD approved medication - 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 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 patients who have been randomized and are actively participating in the study at the time of the amendment approval in their respective country will be eligible to participate in the OLE. Patients in the open label extension will be given the option of extending open-label treatment beyond the initial 2 years 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
Exclusion criteria: Part 1 - 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Double-blind treatment period (Part 1): To evaluate the efficacy of gantenerumab administered to patients by SC injection over 100 weeks vs. placebo on measures of cognition (ADAS-Cog) and function (ADCS-ADL). Based on recent findings from the SCarlet RoAD study and from other studies on anti-amyloid antibodies, the study has been amended to allow for higher doses of gantenerumab to be examined in an open-label extension Open-label extension (Part 2): To evaluate the safety and tolerability of gantenerumab at higher doses (up to 1200 mg) focusing on physical and neurologic examinations, vital signs, blood safety tests, ECG, and AE monitoring;Secondary Objective: Part 1: 1. To evaluate the benefits of gantenerumab vs 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 • Change from baseline at Week 104 in CDR-SB • ADAS-Cog responder • Disease pathology biomarkers 2. Additional secondary endpoints · Global: Effect on severity of dementia and global measures of cognition and function · Cognition: Effect on cognition · Behavior: Effect on behavioral and neuropsychological symptoms of AD · Other AD symptoms and effects: Effect of gantenerumab on health related QoL, patient-individualized goal achievement, on caregiver emotional well-being, on the amount of assistance patients with dementia require in performing daily activities Part 2: To evaluate the effect of higher doses of gantenerumab on imaging biomarkers, CSF biomarkers, and clinical outcome measures, and to explore the PK at the higher doses ;Timepoint(s) of evaluation of this end point: Double-blind treatment period (Part 1): 1-2.Up to 2 years Open label extension (Part 2): 3.Up to approximately 4 years of open label ;Primary end point(s): Double-blind treatment period (part 1): 1. Mean change in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) sco | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Double-blind treatment period (Part 1) 1.Change in biomarkers (t-tau, p-tau, Abeta 1-42 levels) in cerebral spinal fluid 2. Change in MRI volumetry, assessed on structural MRI 3. Change in Clinical Dementia Rating (CDR-SB/CDR-GS) 4. Change in neuropsychiatric behaviour: Neuropsychiatric Inventory (NPI) total and domain scores 5. Change in cognition: MMSE total score 6. Safety: Incidence of adverse events, serious adverse events and treatment discontinuations 7. Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) 8. ADAS-Cog responder Open label extension (Part 2): 9. Explore the effect of gantenerumab on clinical outcome measures and biomarker measures ;Timepoint(s) of evaluation of this end point: Double-blind treatment period (part 1): 1-8. From baseline to Week 104 Open-label extension (part 2): 9. at OLE week 104 | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, 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
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed