Overview

This trial is active, not recruiting.

Condition alzheimer's disease
Treatments aducanumab (recombinant, fully human anti-aβ igg1 mab), placebo
Phase phase 1
Sponsor Biogen
Start date October 2012
End date October 2019
Trial size 197 participants
Trial identifier NCT01677572, 2012-000349-10, 221AD103

Summary

The primary objective of this study is to evaluate the safety and tolerability of multiple doses of Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) in participants with prodromal or mild Alzheimer's Disease (AD). The secondary objectives of this study are to assess the effect on cerebral amyloid plaque content as measured by florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging, to assess the multiple dose serum concentrations of Aducanumab and to evaluate the immunogenicity of Aducanumab after multiple dose administration in this population.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
Intravenous doses of low-dose level #1 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for an additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Experimental)
Intravenous doses of low-dose level #2 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for an additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Placebo Comparator)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
placebo
Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Experimental)
Intravenous doses of mid-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for an additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Placebo Comparator)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
placebo
Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Experimental)
Intravenous doses of high-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for an additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Placebo Comparator)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
placebo
Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Experimental)
Intravenous doses of Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to additional 42 doses.
aducanumab (recombinant, fully human anti-aβ igg1 mab) IgG1
Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.
(Placebo Comparator)
Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to additional 42 doses.
placebo
Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for an additional 42 doses.

Primary Outcomes

Measure
Number of Participants with Adverse Events
time frame: Baseline to week 238

Secondary Outcomes

Measure
Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.
time frame: Day 1, Weeks 26, 54, End of year 2, 3, and 4
Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab
time frame: Up to week 238
Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.
time frame: Up to week 238

Eligibility Criteria

Male or female participants from 50 years up to 90 years old.

Key Inclusion Criteria: - Participants must be ambulatory. - Participants must meet the following core clinical criteria as determined by the Investigator: Prodromal Alzheimer's Disease (AD) (all of the criteria must apply): - Mini Mental State Examination (MMSE) scores between 24-30 (inclusive) - a spontaneous memory complaint - objective memory loss defined as a free recall score of ≤27 on the Free and Cued Selective Reminding Test (FCSRT) - a global Clinical Dementia Rating Scale (CDR) score of 0.5 - absence of significant levels of impairment in other cognitive domains - essentially preserved activities of daily living, and an absence of dementia. OR Mild Alzheimer's Disease (AD) criteria (all criteria must apply): - Mini Mental State Examination (MMSE) scores between 20-26 (inclusive) - a global Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0 - meeting the National Institute on Aging-Alzheimer's Association core clinical criteria for probable AD. - Participants must have a positive florbetapir positron emission tomography (PET) amyloid scan. - Participants must consent to apolipoprotein E (ApoE) genotyping. - Apart from clinical diagnosis of Alzheimer's Disease (AD), participant must be in good health. - Must have a reliable informant or caregiver. Key Exclusion Criteria: - Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the participant'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. - Seizure in the past 3 years. - Poorly controlled diabetes mellitus. - 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. - Brain MRI showing evidence of acute or sub-acute micro or macrohemorrhage, greater than 4 microhemorrhages, cortical infarct or greater than one 1 lunar infarct. - Any contraindications to brain MRI or positron emission tomography (PET) scans. - Negative positron emission tomography (PET) scan with any amyloid-targeting ligand within 48 weeks of Screening. - Clinically significant 12-lead electrocardiogram (ECG) abnormalities. - Alcohol or substance abuse in past 1 year. - Taking blood thinners (except for aspirin at a prophylactic dose or less) - Have changes in medications or doses of medication in past 4 weeks. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Additional Information

Official title A Randomized, Double-Blinded, Placebo-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB037 in Subjects With Prodromal or Mild Alzheimer's Disease
Description The study consists of a placebo-controlled period to study week 54, followed by a long-term extension to study week 220. The placebo-controlled period is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel, 2 additional treatment arms beginning in parallel, and the last 2 treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period for up to 42 additional doses of active drug.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Biogen.