Clinical trial NCT03056729: Single-Ascending-Dose Study of BIIB076 in Healthy Volunteers and Participants With Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Healthy Volunteer
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-02-17
Enrollment: 46
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 20
Secondary outcomes:
measure: BIIB076 serum pharmacokinetics (PK) concentration levels
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Area under the concentration-time curve from time zero to infinity (AUCinf)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Maximum observed concentration (Cmax)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Time to reach maximum observed concentration (Tmax)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Terminal elimination half-life (t1/2)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Clearance (CL)
timeFrame: Up to Week 20
measure: PK parameter of BIIB076: Volume of distribution (Vd)
timeFrame: Up to Week 20
measure: Number of participants with positive serum BIIB076 antibodies
timeFrame: Up to Week 20
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Saint Louis
country: United States
facility: St Louis Clinical Trial
state: Missouri
city: Dallas
country: United States
facility: Covance Dallas CRU
state: Texas
city: Madison
country: United States
facility: Covance CRU
state: Wisconsin
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: