Single-Ascending-Dose Study of BIIB076 in Healthy Volunteers and Participants With Alzheimer's Disease

NCT03056729 | Completed Phase 1 FDA Drug

• 1 other identifier: 243HV101
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 8

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of single-ascending intravenous (IV) infusions of BIIB076 in healthy volunteers and participants with Alzheimer's disease (AD). A secondary objective of the study for both healthy volunteers and participants with AD is to assess the serum pharmacokinetic(s) (PK) profile of BIIB076 after single-dose administration. Another secondary objective is to evaluate the immunogenicity of BIIB076 in serum after single-dose administration.

Conditions

Alzheimer's Disease; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Safety surveillance

  Baseline up to Week 20

Secondary Outcomes (9)

• BIIB076 serum pharmacokinetics (PK) concentration levels

  Up to Week 20

• PK parameter of BIIB076: Area under the concentration-time curve from time zero to infinity (AUCinf)

  Up to Week 20

• PK parameter of BIIB076: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast)

  Up to Week 20

• PK parameter of BIIB076: Maximum observed concentration (Cmax)

  Up to Week 20

• PK parameter of BIIB076: Time to reach maximum observed concentration (Tmax)

  Up to Week 20

Study Arms (6)

Cohort HV1

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Cohort HV2

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Cohort HV3

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Cohort HV4

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Cohort HV5

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Cohort AD1

EXPERIMENTAL

Drug: BIIB076; Drug: Placebo

Interventions

BIIB076 DRUG

Administered as single intravenous (IV) infusion

Cohort AD1; Cohort HV1; Cohort HV2; Cohort HV3; Cohort HV4; Cohort HV5

Placebo DRUG

Administered as single IV infusion

Cohort AD1; Cohort HV1; Cohort HV2; Cohort HV3; Cohort HV4; Cohort HV5

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be in good health as determined by the Investigator, based on medical history and Screening evaluations.
• Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD according to the National Institutes of Aging-Alzheimer's Association \[McKhann 2011\], and in addition must have the following:
• Clinical Dementia Rating (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD.
• CDR Memory Box Score of ≥0.5.
• Mini-Mental State Examination score between 18 and 30 (inclusive) at Screening.
• Must have amyloid beta positivity confirmed at Screening

You may not qualify if:

• Brain MRI findings that might pose a risk to the participant, or might prevent a satisfactory MRI assessment for safety monitoring.
• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator.
• Current enrollment in any other drug, biologic, device, or clinical study or treatment with an investigational drug or approved therapy for investigational use within 30 days (6 months for biologics) or 5 half-lives, whichever is longer, prior to Day-1.
• Contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed).
• Contraindications to having an Lumbar Puncture (LP).
• Any medical or neurologic/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment (e.g.,current history of substance abuse, uncontrolled vitamin B12 deficiency or uncontrolled thyroid disease, stroke or other cerebrovascular condition, Parkinson's disease, Lewy body dementia, or frontotemporal dementia or head trauma), or could lead to discontinuation, noncompliance with study assessments, or safety concerns.
• Diagnosis within 1 year prior to Screening and/or evidence of clinically significant (in the opinion of the Investigator) psychiatric illness including uncontrolled major depression, bipolar affective disorder, other psychiatric illness, and suicidal ideation.
• Any documented prior history of chronic schizophrenia.
• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary (including chronic obstructive pulmonary disease), neurologic, dermatologic, or renal disease, or other major disease, as determined by the Investigator.
• Use of any medications for the treatment of comorbid conditions that have not been stable for at least 8 weeks prior to Day -1 and/or that are not expected to remain stable for the duration of the study.
• Current enrollment or plan to enroll in any other drug, biologic, device, or clinical study or treatment with an investigational drug or approved therapy for investigational use within 30 days (6 months for biologics) or 5 half-lives, whichever is longer, prior to Day-1.
• Contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed).
• Brain MRI findings that might be a contributing cause of the participant's dementia, might pose a risk to the participant, or might prevent a satisfactory MRI assessment for safety monitoring.
• Contraindications to having an LP.
• History of, or ongoing chronic uncontrolled hypertension

Sponsors & Collaborators

• Biogen: lead

Study Sites (8)

MD Clinical

Hallandale, Florida, 33009, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

St Louis Clinical Trial

St Louis, Missouri, 63141, United States

Location

Covance Dallas CRU

Dallas, Texas, 75247, United States

Location

Covance CRU

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 17, 2017
• Study Start: February 17, 2017
• Primary Completion: March 3, 2020
• Study Completion: March 3, 2020
• Last Updated: March 24, 2020

Record last verified: 2020-03

Locations

US (8)