Early Alzheimer's Disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: - Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have: - A Clinical Dementia Rating (CDR)-Global Score of 0.5. - A Repeatable Battery for Assessment of Neuropsychological Status (RBANS) score of 85 or lower indicative of objective cognitive impairment - An MMSE score between 24 and 30 (inclusive) - Must have a positive amyloid Positron Emission Tomography (PET) scan - Must consent to apolipoprotein E (ApoE) genotyping - Must have stable symptomatic AD medications - Must have a reliable informant or caregiver LTE specific Criteria at week 78: - Must have completed the placebo-controlled period of the study. - Must (or the subject’s legally authorized representative) understand the purpose and risks of the study and provide signed consent (or assent) - Apart from a clinical diagnosis of AD, subject must be in good health as determined by the Investigator, based on medical history. - Must have the ability to comply with procedures for protocol-related tests. - Must have reliable informant or caregiver NOTE: Other protocol defined Inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 750
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: - Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment - Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year - Clinically significant psychiatric illness in past 6 months - History of unstable angina, myocardial infarction, chronic heart failure, or clinical significant conduction abnormalities within 1 year prior to Screening - Indication of impaired renal or liver function - Have human immunodeficiency virus (HIV) infection - Have a significant systematic illness or infection in past 30 days - Relevant brain haemorrhage, bleeding disorder and cardiovascular abnormalities - Any contraindications to brain magnetic resonance imaging (MRI) or PET scans - Alcohol or substance abuse in past 1 year - Taking blood thinners (except for aspirin at a prophylactic dose or less) - Use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 Subjects will be excluded from entering the LTE if at Week 78 they have: - any medical or psychiatric contraindication or clinically significant abnormality that, in the opinion of the Investigator, will substantially increase the risk associated with the subject's participation in the study. NOTE: Other protocol defined Exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Placebo-controlled period: To evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the CDR-SB score as compared with placebo in subjects with early AD. Long-term Extension: To evaluate the long-term safety and tolerability profile of aducanumab in subjects with early AD. ? To evaluate the long-term efficacy of aducanumab treatment as measured by clinical, radiological, and additional assessments reported by the subject and informant/care partner.;Secondary Objective: To assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by the MMSE. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by ADAS-Cog 13. To assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by ADCS-ADL-MCI. ;Primary end point(s): Primary endpoint: Change from baseline in CDR-SB score at Week 78. LTE period endpoints: The incidence of AEs and/SAEs; brain MRI findings (including the incidence of ARIA-E and ARIA-H); and the incidence of anti-aducanumab antibodies in serum over the placebo-controlled and LTE periods of the study. Change in the following measures over the placebo-controlled and LTE periods of the study: CDR-SB score. MMSE score. ADAS-Cog 13 score. ADCS-ADL-MCI score. Amyloid PET signal (in a subset of subjects). Whole brain volume, hippocampal volume, ventricular volume, and cortical gray matter volume measured by MRI. Functional connectivity as measured by tf-fMRI (where available). Cerebral blood flow as measured by ASL-MRI (where available). Disease-related biomarker levels in CSF which will include, but are not limited to, amyloid and tau proteins (in a subset of subjects). Disease-related biomarker levels in blood which may include, but are not limited to, amyloid and tau proteins. NPI-10 total score. Informant-ra | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline in MMSE score at Week 78. Change from baseline in ADAS-Cog 13 score at Week 78. Change from baseline in ADCS-ADL-MCI score at Week 78.;Timepoint(s) of evaluation of this end point: Week 78 | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Sweden, Taiwan, United Kingdom, United States
Outcome results
None listed