Clinical trial NCT02106897: Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Single Doses and Multiple Doses of BIIB059 (Litifilimab) in Healthy Volunteers and Participants With Systemic Lupus Erythematosus
Official title: A Single-Ascending-Dose and Multiple-Ascending-Dose Study of BIIB059 in Healthy Volunteers and Subjects With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Healthy Volunteers
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2014-04-08
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of Parts 1 and 2 is to evaluate the safety and tolerability of either single-ascending intravenous (IV) doses or a single subcutaneous (SC) dose of BIIB059 (litifilimab) in healthy volunteers (HV), and a single IV dose in participants with Systemic Lupus Erythematosus (SLE). The primary objective of Part 3 is to evaluate the safety and tolerability of multiple SC doses of BIIB059 in healthy volunteers and in participants with SLE.

Secondary objectives of Parts 1 and 2 are as follows: To estimate the PK parameters of single-ascending IV doses of BIIB059 in healthy volunteers and a single IV dose of BIIB059 in participants with SLE; To estimate the PK parameters and bioavailability (F) of a single SC dose of BIIB059 in healthy volunteers; To evaluate the immunogenicity of BIIB059 administered to healthy volunteers and participants with SLE. Secondary objectives of Part 3 are as follows: To estimate the PK parameters of multiple SC doses of BIIB059 in healthy volunteers and in participants with SLE; To evaluate the immunogenicity of BIIB059 administered SC to healthy volunteers and participants with SLE.

Detailed description: Part 1 (single ascending dose in healthy volunteers) has closed to enrollment.

Eligibility criteria: Part 1: Key Inclusion Criteria For Healthy Volunteers:

* Be in good health as determined by the Investigator, based on medical history, physical examination, and 12-lead ECG.
* Body mass index (BMI) between 18 and 30 kg/m2 and body weight ≥45 kg.

Part 1: Key Exclusion Criteria For Healthy Volunteers:

* History of or positive test results at screening for the following: for human immunodeficiency virus (HIV), hepatitis C virus antibody (HCV Ab), hepatitis B virus (defined as positive for hepatitis B surface antigen \[HBsAg\] or hepatitis B core antibody \[HBcAb\]).
* - History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization.
* History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug.
* History of any clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
* Any live or attenuated immunization/vaccination within 1 month prior to randomization or planned to occur during the study period.
* Blood donation (1 unit or more) within 1 month prior to randomization.
* Vigorous exercise (e.g., jogging, swimming laps, heavy gardening, hiking uphill, etc.) within 48 hours prior to Day -1

Part II: Key Inclusion Criteria for SLE Participants:

* Definite SLE for at least 6 months duration or anti-dsDNA antibody, prior to screening.
* Presence of active lupus skin disease including acute, sub acute, and/or chronic cutaneous lupus (e.g., discoid) at the time of screening and randomization.
* BMI between 18 and \<40 kg/m2 and body weight ≥45 kg.

Part II: Key Exclusion Criteria for SLE Participants:

* Active neuropsychiatric SLE including but not limited to the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes.
* History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization.
* Symptoms of bacterial or viral infection (including upper respiratory tract infection) within 28 days prior to randomization.
* History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug.
* Evidence of skin conditions other than lupus skin disease (e.g., eczema) at screening or at the time of randomization that would interfere with evaluations of the effect of study treatment on lupus skin disease.
* Treatment with oral prednisone \>15 mg daily (or equivalent). Any prednisone regimen must be stable for at least 28 days before randomization and expected to remain stable for the duration of the study.
* Treatment with any antibiotics within 14 days prior to randomization.

Part IIIa: Key Inclusion Criteria for Healthy Volunteers :

* Must be in good health as determined by the Investigator, based on medical history, physical examination, and 12-lead ECG.
* Must have a body mass index (BMI) between 18 and 30 kg/m2 and body weight ≥45 kg.

Part IIIa: Key Exclusion Criteria for Healthy Volunteers:

* History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization
* History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study treatment.
* Treatment with any antibiotics within 14 days prior to randomization.

Part IIIb: Key Inclusion Criteria for SLE Participants:

* Definite SLE for at least 6 months duration prior to screening
* Presence of active lupus skin disease including acute, subacute, and/or chronic cutaneous lupus (e.g., discoid), and/or hypocomplementemia , and/or positive anti-dsDNA antibody at the time of screening.
* Must have a BMI between 18 and \<40 kg/m2 and body weight ≥45 kg.

Part IIIb: Key Exclusion Criteria for SLE Participants:

* Active neuropsychiatric SLE including but not limited to the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes.
* History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization.
* History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug.
* Treatment with any antibiotics within 14 days prior to randomization.

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: Up to Week 32
Secondary outcomes:
measure: Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of BIIB059
timeFrame: Up to Week 32
measure: Maximum Observed Concentration (Cmax) of BIIB059
timeFrame: Up to Week 32
measure: Time to Reach Maximum Observed Concentration (Tmax) of BIIB059
timeFrame: Up to Week 32
measure: Terminal Elimination Half-Life (t1/2) of BIIB059
timeFrame: Up to Week 32
measure: Clearance (CL) of BIIB059
timeFrame: Up to Week 32
measure: Apparent Clearance (CL/F) of BIIB059
timeFrame: Up to Week 32
measure: Volume of Distribution (Vss) of BIIB059
timeFrame: Up to Week 32
measure: Apparent Volume of Distribution (Vz/F) of BIIB059
timeFrame: Up to Week 32
measure: Bioavailability (F) for a single SC dose of BIIB059
timeFrame: Up to Week 32
measure: Absorption Rate Profile for a Single SC Dose of BIIB059
timeFrame: Up to Week 32
measure: Number of Participants Who Develop Serum Anti-BIIB059 Antibodies
timeFrame: Up to Week 32
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Great Neck
country: United States
facility: Research Site
state: New York
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Furie R, Werth VP, Merola JF, Stevenson L, Reynolds TL, Naik H, Wang W, Christmann R, Gardet A, Pellerin A, Hamann S, Auluck P, Barbey C, Gulati P, Rabah D, Franchimont N. Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. J Clin Invest. 2019 Mar 1;129(3):1359-1371. doi: 10.1172/JCI124466. Epub 2019 Feb 18.