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

NCT01677572 | Terminated Phase 1 DMC

• 2 other identifiers: 221AD1032012-000349-10
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 32

Brief 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.

Conditions

Alzheimer's Disease

Keywords

Aducanumab; BIIB037

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events

  Baseline to week 518

Secondary Outcomes (3)

• Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.

  Day 1, Weeks 26, 54, End of year 2, 3, and 4

• Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab

  Up to week 518

• Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.

  Up to week 518

Study Arms (9)

Low-dose #1 Aducanumab

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 up to an additional 112 doses.

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

Low-dose #2 Aducanumab

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 up to an additional 112 doses.

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

Placebo (low dose group)

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 an additional 112 doses.

Drug: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb); Drug: Placebo

Mid-dose Aducanumab

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 up to an additional 112 doses.

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

Placebo (mid dose group)

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 an additional 112 doses.

Drug: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb); Drug: Placebo

High-dose Aducanumab

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 up to an additional 112 doses.

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

Placebo (high dose group)

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 an additional 112 doses.

Drug: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb); Drug: Placebo

Aducanumab Titration

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 an additional 112 doses.

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

Placebo (Titration Group)

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 an additional 112 doses.

Drug: Placebo

Interventions

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

Also known as: IgG1, anti-A* mAb, Fully human

Aducanumab Titration; High-dose Aducanumab; Low-dose #1 Aducanumab; Low-dose #2 Aducanumab; Mid-dose Aducanumab; Placebo (high dose group); Placebo (low dose group); Placebo (mid dose group)

Placebo 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.

Placebo (Titration Group); Placebo (high dose group); Placebo (low dose group); Placebo (mid dose group)

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Biogen: lead

Study Sites (32)

NNS Clinical Research, LLC

Tucson, Arizona, 85704, United States

Location

Senior Clinical Trials, Inc.

Laguna Hills, California, 92653, United States

Location

Torrance Clinical Research Institute, Inc.

Lomita, California, 90717, United States

Location

Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Pacific Neuroscience Medical Group

Oxnard, California, 93030, United States

Location

Pacific Research Network, Inc.

San Diego, California, 92103, United States

Location

San Francisco Clinical Research Center

San Francisco, California, 94109, United States

Location

Stanford University Medical Center

Stanford, California, 94304, United States

Location

Alzheimer's Disease Research Unit, Yale University

New Haven, Connecticut, 06520, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20057, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

MD Clinical Trials, Inc.

Hallandale, Florida, 33009, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Galiz Research, LLC

Miami Springs, Florida, 33166, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

Infinity Clinical Research, Inc.

Sunrise, Florida, 33351, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Stedman Clinical Trials, LLC

Tampa, Florida, 33613, United States

Location

Neurostudies.net, LLC

Decatur, Georgia, 30033, United States

Location

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, 60007, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

St. Louis Clinical Trials, LLC

St Louis, Missouri, 63118, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

CRI Lifetree

Marlton, New Jersey, 08053, United States

Location

Advanced Memory Research Institute of NJ

Toms River, New Jersey, 08755, United States

Location

Empire Neurology, PC

Latham, New York, 12110, United States

Location

Insight Clinical Trials LLC

Beachwood, Ohio, 44122, United States

Location

Summit Research Network (Oregon) Inc.

Portland, Oregon, 97210, United States

Location

Brown Hospital

East Providence, Rhode Island, 02906, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Related Publications (2)

• 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.

  PMID: 38567735 DERIVED

• 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.

  PMID: 27582220 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

aducanumab; Immunoglobulin G

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: September 3, 2012
• Study Start: October 5, 2012
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

US (32)