Single Ascending Dose Study of BIIB037 in Participants With Alzheimer's Disease

A Randomized, Blinded, Placebo-Controlled Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB037 in Subjects With Mild to Moderate Alzheimer's Disease

The primary objective of the study is to evaluate the safety and tolerability of a range of BIIB037 doses administered as single intravenous (IV) infusions in participants with mild to moderate Alzheimer's Disease (AD). Secondary objectives of this study in this study population are to assess the pharmacokinetics(PK) and to evaluate the immunogenicity of BIIB037 after single-dose administration.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: BIIB037; Other: Placebo

Detailed Description

BIIB037 is an investigational product being developed as a treatment for Alzheimer's disease (AD). BIIB037 is a fully human immunoglobulin gamma 1 (IgG1) monoclonal antibody that is selective for the fibrillar form of beta amyloid (Aß).

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Insight Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Must be ambulatory

• Must have a clinical diagnosis of Alzheimer's Disease (AD) consistent with the following:

  1. Probable Alzheimer's Disease (AD), according to National Institute of Neurological and Communicative Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria [McKhann et al. 1984].
  2. Dementia of Alzheimer's type, according to Diagnostic and Statistical Manual of Mental Disorders-Text Revision (DSM IV TR) criteria [American Psychiatric Association 2000]
• Subject (or subject's permanent caregiver) has the ability to understand the purpose and risks of the study and provide signed and dated informed consent (or assent) and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
• Must have a Mini Mental State Examination (MMSE) score of 14 to 26 inclusive.

Key Exclusion Criteria:

• Any medical or neurological condition other than Alzheimer's Disease (AD) that in the opinion of the Investigator could be a contributing cause of the subject's dementia (e.g., medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, diffuse Lewy body disease, head trauma).
• History within the past 6 months or evidence of clinically significant psychiatric illness (e.g., major depression, schizophrenia, or bipolar affective disorder).
• Subject currently lives in a nursing home.
• Blood donation (1 unit or more) within the 1 month prior to Screening
• Participation in any other drug, biologic, device, or clinical study or treatment with any investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to Screening, and/or participation in any other clinical study involving experimental medications for AD within the 60 days (or 5 half lives, whichever is longer) prior to Screening.
• Any contraindications to having a brain Magnetic Resonance Imaging (MRI) e.g., pacemaker; Non-Magnetic Resonance Imaging (MRI)-compatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB037; A single dose of BIIB037 by intravenous infusion.	Drug: BIIB037; Participants receive a single dose of BIIB037 by intravenous (IV) infusion in cohorts assigned to the following ascending doses: .03 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, and 60 mg/kg.; Other Names: Aducanumab; fully human IgG1 anti-Aβ mAb
Placebo Comparator: Placebo; A single dose of placebo matching BIIB037 by intravenous infusion.	Other: Placebo; Participants receive a single dose of matching BIIB037 placebo by intravenous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Significant assessments reported as AEs or SAEs include clinical laboratory assessments and vital signs, physical and neurological examination, 12-lead electrocardiogram (ECG), and brain MRI findings (including the occurrence of vasogenic edema and incident hemorrhage).	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve from Time Zero Extrapolated to Infinity [AUC0-∞]	6 months
Area Under the Curve from Time 0 to Time of the Last Measurable Concentration [AUC0-tlast]	6 months
Maximum Concentration [Cmax] of BIIB037	6 Months
Time to Cmax [Tmax]	6 Months
Elimination Half-life [t1/2]	6 Months
Clearance [Cl]	6 Months
Incidence of Anti-BIIB037 Antibodies in Serum	6 Months

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Ferrero J, Williams L, Stella H, Leitermann K, Mikulskis A, O'Gorman J, Sevigny J. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2016 Jun 20;2(3):169-176. doi: 10.1016/j.trci.2016.06.002. eCollection 2016 Sep.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: June 30, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimate): July 19, 2011

Study Record Updates

• Last Update Posted (Estimate): March 23, 2015
• Last Update Submitted That Met QC Criteria: March 19, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 221AD101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No