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

Sponsor
Biogen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01677572
Collaborator
(none)
197
Enrollment
32
Locations
9
Arms
81.8
Actual Duration (Months)
6.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)
  • Drug: Placebo
 Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
197 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 5, 2012
Actual Primary Completion Date :
Jul 31, 2019
Actual Study Completion Date :
Jul 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: 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.
Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    		•
    Experimental: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    		•
    Placebo Comparator: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    		•
    Placebo Comparator: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    		•
    Placebo Comparator: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    • 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.
    Experimental: 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.

    Drug: 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.
    Other Names:
  • IgG1
  • anti-A* mAb
  • Fully human

    		•
    Placebo Comparator: 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.

    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.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Adverse Events [Baseline to week 518]

    Secondary Outcome Measures

    1. 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]

    2. Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab [Up to week 518]

    3. Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum. [Up to week 518]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 NNS Clinical Research, LLC Tucson Arizona United States 85704
    2 Senior Clinical Trials, Inc. Laguna Hills California United States 92653
    3 Torrance Clinical Research Institute, Inc. Lomita California United States 90717
    4 Collaborative Neuroscience Network, LLC Long Beach California United States 90806
    5 University of California, Los Angeles Los Angeles California United States 90095
    6 Pacific Neuroscience Medical Group Oxnard California United States 93030
    7 Pacific Research Network, Inc. San Diego California United States 92103
    8 San Francisco Clinical Research Center San Francisco California United States 94109
    9 Stanford University Medical Center Stanford California United States 94304
    10 Alzheimer's Disease Research Unit, Yale University New Haven Connecticut United States 06520
    11 Georgetown University Hospital Washington District of Columbia United States 20057
    12 Brain Matters Research, Inc. Delray Beach Florida United States 33445
    13 Neuropsychiatric Research Center of Southwest Florida Fort Myers Florida United States 33912
    14 MD Clinical Trials, Inc. Hallandale Beach Florida United States 33009
    15 Galiz Research, LLC Miami Springs Florida United States 33166
    16 Miami Jewish Health Systems Miami Florida United States 33137
    17 Compass Research, LLC Orlando Florida United States 32806
    18 Infinity Clinical Research, Inc. Sunrise Florida United States 33351
    19 Axiom Clinical Research of Florida Tampa Florida United States 33609
    20 Stedman Clinical Trials, LLC Tampa Florida United States 33613
    21 Neurostudies.net, LLC Decatur Georgia United States 30033
    22 Alexian Brothers Neurosciences Institute Elk Grove Village Illinois United States 60007
    23 Indiana University School of Medicine Indianapolis Indiana United States 46202
    24 St. Louis Clinical Trials, LLC Saint Louis Missouri United States 63118
    25 Memory Enhancement Center of America, Inc. Eatontown New Jersey United States 07724
    26 CRI Lifetree Marlton New Jersey United States 08053
    27 Advanced Memory Research Institute of NJ Toms River New Jersey United States 08755
    28 Empire Neurology, PC Latham New York United States 12110
    29 Insight Clinical Trials LLC Beachwood Ohio United States 44122
    30 Summit Research Network (Oregon) Inc. Portland Oregon United States 97210
    31 Brown Hospital East Providence Rhode Island United States 02906
    32 Rhode Island Hospital Providence Rhode Island United States 02903

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT01677572
    Other Study ID Numbers:
    • 221AD103
    • 2012-000349-10
    First Posted:
    Sep 3, 2012
    Last Update Posted:
    Aug 3, 2020
    Last Verified:
    Jul 1, 2020
    Keywords provided by Biogen
    Aducanumab
    BIIB037
    Additional relevant MeSH terms:
    Alzheimer Disease
    Immunoglobulin G

    Study Results

    No Results Posted as of Aug 3, 2020