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

Alzheimer's Disease Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01677572
• Other study ID #: 221AD103
• Secondary ID: 2012-000349-10
• Status: Terminated
• Phase: Phase 1
• Start date: October 5, 2012
• Est. completion date: July 31, 2019

Study information

• Verified date: July 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 197
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Aducanumab (recombinant, fully human anti-Aß 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.
• 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.

Locations

Country	Name	City	State
United States	Insight Clinical Trials LLC	Beachwood	Ohio
United States	Neurostudies.net, LLC	Decatur	Georgia
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Brown Hospital	East Providence	Rhode Island
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Neurosciences Institute	Elk Grove Village	Illinois
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	MD Clinical Trials, Inc.	Hallandale Beach	Florida
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Senior Clinical Trials, Inc.	Laguna Hills	California
United States	Empire Neurology, PC	Latham	New York
United States	Torrance Clinical Research Institute, Inc.	Lomita	California
United States	Collaborative Neuroscience Network, LLC	Long Beach	California
United States	University of California, Los Angeles	Los Angeles	California
United States	CRI Lifetree	Marlton	New Jersey
United States	Miami Jewish Health Systems	Miami	Florida
United States	Galiz Research, LLC	Miami Springs	Florida
United States	Alzheimer's Disease Research Unit, Yale University	New Haven	Connecticut
United States	Compass Research, LLC	Orlando	Florida
United States	Pacific Neuroscience Medical Group	Oxnard	California
United States	Summit Research Network (Oregon) Inc.	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	St. Louis Clinical Trials, LLC	Saint Louis	Missouri
United States	Pacific Research Network, Inc.	San Diego	California
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Stanford University Medical Center	Stanford	California
United States	Infinity Clinical Research, Inc.	Sunrise	Florida
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	NNS Clinical Research, LLC	Tucson	Arizona
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events		Baseline to week 518
Secondary	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
Secondary	Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab		Up to week 518
Secondary	Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.		Up to week 518