Single and Multiple Ascending Dose Study of Aducanumab (BIIB037) in Japanese Participants With Alzheimer's Disease (PROPEL)

A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Aducanumab (BIIB037) in Japanese Subjects With Mild to Moderate Alzheimer's Disease

The primary objective of the study is to evaluate the safety and tolerability of single and multiple intravenous (IV) infusions of Aducanumab in Japanese participants with mild to moderate Alzheimer's Disease (AD). The secondary objectives of this study are as follows: To evaluate the serum pharmacokinetics (PK) of Aducanumab after single and multiple intravenous (IV) infusions of Aducanumab; To evaluate the effect of single and multiple IV infusions of Aducanumab on immunogenicity.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan
    • Research Site
  • Ehime
    • Toon, Ehime, Japan
      • Research Site
  • Hyogo
    • Kobe, Hyogo, Japan
      • Research Site
  • Kanagawa
    • Kamakura, Kanagawa, Japan
      • Research Site
  • Saga
    • Kanzaki, Saga, Japan
      • Research Site
  • Tokoyo
    • Kodaira, Tokoyo, Japan
      • Research Site
    • Shinjuku, Tokoyo, Japan
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 81 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 mild to moderate AD
• Must be in good health as determined by the Investigator, based on medical history and Screening assessments
• Must have a caregiver who, understands the study and assents to accompany the subject to all study site visits, provide information to the Investigator/study site staff, specifically about cognitive abilities and AEs/SAEs and return for per-protocol follow-up visits and procedures
• Must consent to blood sample collection for deoxyribonucleic acid (DNA; genotyping) and ribonucleic acid (RNA; for potential future analysis).

Key Exclusion Criteria:

• Any medical or neurological condition (other than AD) that in the opinion of the Investigator could be a contributing cause of the subject's dementia
• Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening
• Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within the 3 months prior to Day 1
• History of unstable angina, myocardial infarction, chronic heart failure
• Chronic, uncontrolled hypertension
• History of seizure within 3 years prior to Screening
• History within the past 6 months or evidence of clinically significant psychiatric illness
• History of severe allergic or anaphylactic reactions, or history of hypersensitivity to any of the inactive ingredients in the drug product

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: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; IV infusion in cohorts assigned to low dose 1; 1 participant per cohort will receive placebo	Drug: Aducanumab; As described in the treatment arm; Drug: Placebo; IV administration of 0.9% sodium chloride
Experimental: Cohort 2; IV infusion in cohorts assigned to low dose 2; 1 participant per cohort will receive placebo	Drug: Aducanumab; As described in the treatment arm; Drug: Placebo; IV administration of 0.9% sodium chloride
Experimental: Cohort 3; IV infusion in cohorts assigned to high dose; 1 participant per cohort will receive placebo	Drug: Aducanumab; As described in the treatment arm; Drug: Placebo; IV administration of 0.9% sodium chloride
Experimental: Cohort 4; IV infusion in cohorts assigned to mid dose; 1 participant per cohort will receive placebo	Drug: Aducanumab; As described in the treatment arm; Drug: Placebo; IV administration of 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of adverse events (AE) / serious adverse events(SAE)	Up to week 42
Clinically significant changes in vital signs and 12-lead electrocardiogram (ECG) data; abnormalities in neurological and physical examinations	Up to week 42
Brain magnetic resonance imaging (MRI) findings to assess amyloid-related imaging abnormalities (ARIA), including incidence of ARIA-E (edema) or ARIA-H (hemosiderosis)	Up to week 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC0-∞)	Up to 8 weeks post dosing
AUC from time zero to time of the last measurable concentration (AUC0-last)	Up to 8 weeks post dosing
Maximum observed concentration (Cmax)	Up to 8 weeks post dosing
Time to Cmax (Tmax)	Up to 8 weeks post dosing
Elimination half-life (t1/2)	Up to 8 weeks post dosing
Volume of distribution at steady state (Vss)	Up to 8 weeks post dosing
Clearance (CL) after a single IV infusion of aducanumab	Up to 8 weeks post dosing
Incidence of anti-aducanumab antibodies in serum	Up to week 42

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2015
• Primary Completion (Actual): December 9, 2016
• Study Completion (Actual): December 9, 2016

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Actual): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: August 1, 2020

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: 221AD104