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

Primary Purpose

Alzheimer's Disease

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)
Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Aducanumab, BIIB037

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • NNS Clinical Research, LLC
  • Senior Clinical Trials, Inc.
  • Torrance Clinical Research Institute, Inc.
  • Collaborative Neuroscience Network, LLC
  • University of California, Los Angeles
  • Pacific Neuroscience Medical Group
  • Pacific Research Network, Inc.
  • San Francisco Clinical Research Center
  • Stanford University Medical Center
  • Alzheimer's Disease Research Unit, Yale University
  • Georgetown University Hospital
  • Brain Matters Research, Inc.
  • Neuropsychiatric Research Center of Southwest Florida
  • MD Clinical Trials, Inc.
  • Galiz Research, LLC
  • Miami Jewish Health Systems
  • Compass Research, LLC
  • Infinity Clinical Research, Inc.
  • Axiom Clinical Research of Florida
  • Stedman Clinical Trials, LLC
  • Neurostudies.net, LLC
  • Alexian Brothers Neurosciences Institute
  • Indiana University School of Medicine
  • St. Louis Clinical Trials, LLC
  • Memory Enhancement Center of America, Inc.
  • CRI Lifetree
  • Advanced Memory Research Institute of NJ
  • Empire Neurology, PC
  • Insight Clinical Trials LLC
  • Summit Research Network (Oregon) Inc.
  • Brown Hospital
  • Rhode Island Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Low-dose #1 Aducanumab

Low-dose #2 Aducanumab

Placebo (low dose group)

Mid-dose Aducanumab

Placebo (mid dose group)

High-dose Aducanumab

Placebo (high dose group)

Aducanumab Titration

Placebo (Titration Group)

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants with Adverse Events

Secondary Outcome Measures

Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.
Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab
Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.

Full Information

First Posted
August 30, 2012
Last Updated
July 31, 2020
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01677572
Brief Title
Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease
Acronym
PRIME
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns.
Study Start Date
October 5, 2012 (Actual)
Primary Completion Date
July 31, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Aducanumab, BIIB037

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low-dose #1 Aducanumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-dose #2 Aducanumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (low dose group)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Mid-dose Aducanumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (mid dose group)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
High-dose Aducanumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (high dose group)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Aducanumab Titration
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (Titration Group)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)
Other Intervention Name(s)
IgG1, anti-A* mAb, Fully human
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events
Time Frame
Baseline to week 518
Secondary Outcome Measure Information:
Title
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
Title
Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab
Time Frame
Up to week 518
Title
Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.
Time Frame
Up to week 518

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
NNS Clinical Research, LLC
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Senior Clinical Trials, Inc.
City
Laguna Hills
State/Province
California
ZIP/Postal Code
92653
Country
United States
Facility Name
Torrance Clinical Research Institute, Inc.
City
Lomita
State/Province
California
ZIP/Postal Code
90717
Country
United States
Facility Name
Collaborative Neuroscience Network, LLC
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Pacific Neuroscience Medical Group
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Pacific Research Network, Inc.
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
San Francisco Clinical Research Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Alzheimer's Disease Research Unit, Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Brain Matters Research, Inc.
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33445
Country
United States
Facility Name
Neuropsychiatric Research Center of Southwest Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
MD Clinical Trials, Inc.
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Galiz Research, LLC
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Miami Jewish Health Systems
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Infinity Clinical Research, Inc.
City
Sunrise
State/Province
Florida
ZIP/Postal Code
33351
Country
United States
Facility Name
Axiom Clinical Research of Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Stedman Clinical Trials, LLC
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Neurostudies.net, LLC
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Alexian Brothers Neurosciences Institute
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
St. Louis Clinical Trials, LLC
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63118
Country
United States
Facility Name
Memory Enhancement Center of America, Inc.
City
Eatontown
State/Province
New Jersey
ZIP/Postal Code
07724
Country
United States
Facility Name
CRI Lifetree
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Name
Advanced Memory Research Institute of NJ
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
Empire Neurology, PC
City
Latham
State/Province
New York
ZIP/Postal Code
12110
Country
United States
Facility Name
Insight Clinical Trials LLC
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Summit Research Network (Oregon) Inc.
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Brown Hospital
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27582220
Citation
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.
Results Reference
derived

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

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