Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease

NCT ID: NCT01677572

Last Updated: 2020-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-05

Study Completion Date

2019-07-31

Brief Summary

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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.

Detailed Description

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The study consists of a placebo-controlled period to study week 54, followed by a long-term extension to study week 518. 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 for the first 3 years of LTE. Furthermore, up until the last participant in Arms 8 and 9 has had his or her last dose in the fifth year of the LTE, eligible participants will be able to continue treatment beyond the third year of the LTE.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Low-dose #1 Aducanumab

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 up to an additional 112 doses.

Group Type EXPERIMENTAL

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Low-dose #2 Aducanumab

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 up to an additional 112 doses.

Group Type EXPERIMENTAL

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo (low dose group)

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 an additional 112 doses.

Group Type PLACEBO_COMPARATOR

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo

Intervention Type DRUG

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 up to an additional 112 doses.

Mid-dose Aducanumab

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 up to an additional 112 doses.

Group Type EXPERIMENTAL

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo (mid dose group)

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 an additional 112 doses.

Group Type PLACEBO_COMPARATOR

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo

Intervention Type DRUG

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 up to an additional 112 doses.

High-dose Aducanumab

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 up to an additional 112 doses.

Group Type EXPERIMENTAL

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo (high dose group)

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 an additional 112 doses.

Group Type PLACEBO_COMPARATOR

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo

Intervention Type DRUG

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 up to an additional 112 doses.

Aducanumab Titration

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 an additional 112 doses.

Group Type EXPERIMENTAL

Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

Intervention Type DRUG

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 up to an additional 112 doses.

Placebo (Titration Group)

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 an additional 112 doses.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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 up to an additional 112 doses.

Interventions

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Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)

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 up to an additional 112 doses.

Intervention Type DRUG

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 up to an additional 112 doses.

Intervention Type DRUG

Other Intervention Names

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IgG1 anti-A* mAb Fully human

Eligibility Criteria

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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.

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.
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

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NNS Clinical Research, LLC

Tucson, Arizona, United States

Site Status

Senior Clinical Trials, Inc.

Laguna Hills, California, United States

Site Status

Torrance Clinical Research Institute, Inc.

Lomita, California, United States

Site Status

Collaborative Neuroscience Network, LLC

Long Beach, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

Pacific Neuroscience Medical Group

Oxnard, California, United States

Site Status

Pacific Research Network, Inc.

San Diego, California, United States

Site Status

San Francisco Clinical Research Center

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Alzheimer's Disease Research Unit, Yale University

New Haven, Connecticut, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Site Status

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, United States

Site Status

MD Clinical Trials, Inc.

Hallandale, Florida, United States

Site Status

Miami Jewish Health Systems

Miami, Florida, United States

Site Status

Galiz Research, LLC

Miami Springs, Florida, United States

Site Status

Compass Research, LLC

Orlando, Florida, United States

Site Status

Infinity Clinical Research, Inc.

Sunrise, Florida, United States

Site Status

Axiom Clinical Research of Florida

Tampa, Florida, United States

Site Status

Stedman Clinical Trials, LLC

Tampa, Florida, United States

Site Status

Neurostudies.net, LLC

Decatur, Georgia, United States

Site Status

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

St. Louis Clinical Trials, LLC

St Louis, Missouri, United States

Site Status

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States

Site Status

CRI Lifetree

Marlton, New Jersey, United States

Site Status

Advanced Memory Research Institute of NJ

Toms River, New Jersey, United States

Site Status

Empire Neurology, PC

Latham, New York, United States

Site Status

Insight Clinical Trials LLC

Beachwood, Ohio, United States

Site Status

Summit Research Network (Oregon) Inc.

Portland, Oregon, United States

Site Status

Brown Hospital

East Providence, Rhode Island, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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Chen T, O'Gorman J, Castrillo-Viguera C, Rajagovindan R, Curiale GG, Tian Y, Patel D, von Rosenstiel P, von Hehn C, Salloway S, Hock C, Nitsch RM, Haeberlein SB, Sandrock A, Singhal P. Results from the long-term extension of PRIME: A randomized Phase 1b trial of aducanumab. Alzheimers Dement. 2024 May;20(5):3406-3415. doi: 10.1002/alz.13755. Epub 2024 Apr 3.

Reference Type DERIVED
PMID: 38567735 (View on PubMed)

Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.

Reference Type DERIVED
PMID: 27582220 (View on PubMed)

Other Identifiers

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2012-000349-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

221AD103

Identifier Type: -

Identifier Source: org_study_id

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