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

Sponsor

Biogen (Industry)

Overall Status

Completed

CT.gov ID

NCT03056729

Collaborator

(none)

Enrollment

Locations

Arms

36.5

Actual Duration (Months)

5.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

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 :

Feb 17, 2017

Actual Primary Completion Date :

Mar 3, 2020

Actual Study Completion Date :

Mar 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

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

	Site	City	State	Country	Postal Code
1	MD Clinical	Hallandale Beach	Florida	United States	33009
2	Bioclinica Research	Orlando	Florida	United States	32806
3	Progressive Medical Research	Port Orange	Florida	United States	32127
4	Hawaii Pacific Neuroscience	Honolulu	Hawaii	United States	96817
5	Indiana University	Indianapolis	Indiana	United States	46202
6	St Louis Clinical Trial	Saint Louis	Missouri	United States	63141
7	Covance Dallas CRU	Dallas	Texas	United States	75247
8	Covance CRU	Madison	Wisconsin	United States	53704

Sponsors and Collaborators

Biogen

Investigators

Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Biogen

ClinicalTrials.gov Identifier:

NCT03056729

Other Study ID Numbers:

243HV101

First Posted:

Feb 17, 2017

Last Update Posted:

Mar 24, 2020

Last Verified:

Mar 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of Mar 24, 2020