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

• ClinicalTrials.gov Identifier: NCT03056729
• Recruitment Status: Active, not recruiting
• First Posted: February 17, 2017
• Last Update Posted: November 12, 2019
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Healthy Volunteer	Drug: BIIB076; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Blinded, Placebo-Controlled, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB076 in Healthy Volunteers and Subjects With Alzheimer's Disease
• Actual Study Start Date: February 17, 2017
• Estimated Primary Completion Date: March 3, 2020
• Estimated Study Completion Date: March 3, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort HV1	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion
Experimental: Cohort HV2	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion
Experimental: Cohort HV3	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion
Experimental: Cohort HV4	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion
Experimental: Cohort HV5	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion
Experimental: Cohort AD1	Drug: BIIB076; Administered as single intravenous (IV) infusion; Drug: Placebo; Administered as single IV infusion

Outcome Measures

Primary Outcome Measures :

1. Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 20 ]
   Safety surveillance

Secondary Outcome Measures :

1. BIIB076 serum pharmacokinetics (PK) concentration levels [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
2. PK parameter of BIIB076: Area under the concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
3. PK parameter of BIIB076: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
4. PK parameter of BIIB076: Maximum observed concentration (Cmax) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
5. PK parameter of BIIB076: Time to reach maximum observed concentration (Tmax) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
6. PK parameter of BIIB076: Terminal elimination half-life (t1/2) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
7. PK parameter of BIIB076: Clearance (CL) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
8. PK parameter of BIIB076: Volume of distribution (Vd) [ Time Frame: Up to Week 20 ]
   Assessment of BIIB076 pharmacokinetics in blood
9. Number of participants with positive serum BIIB076 antibodies [ Time Frame: Up to Week 20 ]
   Serological assessment (of anti-BIIB076 antibodies in blood)

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria - Healthy Participants

• Must be in good health as determined by the Investigator, based on medical history and Screening evaluations.

Key Inclusion Criteria - Participants with Alzheimer's Disease (AD)

• 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

Key Exclusion Criteria - Healthy Participants

• 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).

Key Exclusion Criteria - Participants with Alzheimer's Disease (AD)

• 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
• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class 3 or 4), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Day -1.
• Medications with platelet anti-aggregant or anticoagulant properties, except the use of aspirin at a dose ≤325 mg per day.
• For participants whose eligibility for study entry will be based on cerebral Aβ positivityas determined by amyloid PET (positron emission tomography), contraindication to having a PET scan (e.g., inability to lie flat or still for the duration of the scan) or intolerance to previous PET scans (i.e. previous hypersensitivity reactions to any PET radioligand or imaging agent, failure to participate in and comply with previous PET scans).

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

Contacts and Locations

Locations

United States, Florida

MD Clinical

Hallandale Beach, Florida, United States, 33009

Bioclinica Research

Orlando, Florida, United States, 32806

Progressive Medical Research

Port Orange, Florida, United States, 32127

United States, Hawaii

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States, 96817

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Missouri

St Louis Clinical Trial

Saint Louis, Missouri, United States, 63141

United States, Texas

Covance Dallas CRU

Dallas, Texas, United States, 75247

United States, Wisconsin

Covance CRU

Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT03056729
• Other Study ID Numbers: 243HV101
• First Posted: February 17, 2017
• Last Update Posted: November 12, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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