Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Single Doses and Multiple Doses of BIIB059 in Healthy Volunteers and Participants With Systemic Lupus Erythematosus

A Single-Ascending-Dose and Multiple-Ascending-Dose Study of BIIB059 in Healthy Volunteers and Subjects With Systemic Lupus Erythematosus

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 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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus; Healthy Volunteers
• Intervention / Treatment: Drug: BIIB059; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Research Site
  • New York
    • Great Neck, New York, United States, 11021
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

19

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Cohort 1: BIIB059 0.05 mg/kg IV; BIIB059 0.05 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 2: BIIB059 0.3 mg/kg IV; BIIB059 0.3 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 3: BIIB059 1 mg/kg IV; BIIB059 1 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 4: BIIB059 3 mg/kg IV; BIIB059 3 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 5: BIIB059 10 mg/kg IV; BIIB059 10 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 6: BIIB059 20 mg/kg IV; BIIB059 20 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Experimental: Part 1, Cohort 7: BIIB059 50 mg SC; BIIB059 50 mg SC dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Placebo Comparator: Part 1, Cohort 1-6: Placebo IV; Matching placebo IV dose, Once on Day 1	Drug: Placebo; See Arm Descriptions
Placebo Comparator: Part 1, Cohort 7: Placebo SC; Matching placebo SC dose, Once on Day 1	Drug: Placebo; See Arm Descriptions
Experimental: Part 2, Cohort 8: BIIB059 20 mg/kg IV; BIIB059 20 mg/kg IV dose, Once on Day 1	Drug: BIIB059; See Arm Descriptions
Placebo Comparator: Part 2, Cohort 8: Placebo IV; Matching placebo IV dose, Once on Day 1	Drug: Placebo; See Arm Descriptions
Experimental: Part 3a, Cohort 9: BIIB059 20 mg SC; BIIB059 20 mg SC dose, Every 4 weeks for 2 doses	Drug: BIIB059; See Arm Descriptions
Experimental: Part 3a, Cohort 10: BIIB059 50 mg SC; BIIB059 50 mg SC dose, Every 4 weeks for 2 doses	Drug: BIIB059; See Arm Descriptions
Experimental: Part 3a, Cohort 11: BIIB059 150 mg SC; BIIB059 150 mg SC dose, Every 4 weeks for 2 doses	Drug: BIIB059; See Arm Descriptions
Experimental: Part 3a, Cohort 12: BIIB059 300 mg or less SC; BIIB059 300 mg or less SC dose, Every 2 weeks for 3 doses	Drug: BIIB059; See Arm Descriptions
Placebo Comparator: Part 3a, Cohort 9-12: Placebo SC; Matching placebo SC dose, Every 4 weeks for 2 doses or every 2 weeks for 3 doses	Drug: Placebo; See Arm Descriptions
Experimental: Part 3b, Cohort 13: BIIB059 50 mg SC; BIIB059 50 mg SC dose, Every 4 weeks for 2 doses	Drug: BIIB059; See Arm Descriptions
Experimental: Part 3b, Cohort 14: BIIB059 300 mg or less SC; BIIB059 300 mg or less SC dose, Every 2 weeks for 3 doses	Drug: BIIB059; See Arm Descriptions
Placebo Comparator: Part 3b, Cohort 13-14: Placebo SC; Matching placebo SC dose, Every 4 weeks for 2 doses or every 2 weeks for 3 doses	Drug: Placebo; See Arm Descriptions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants that Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of BIIB059		Up to Week 32
Maximum Observed Concentration (Cmax) of BIIB059		Up to Week 32
Time to Reach Maximum Observed Concentration (Tmax) of BIIB059		Up to Week 32
Terminal Elimination Half-Life (t1/2) of BIIB059		Up to Week 32
Clearance (CL) of BIIB059		Up to Week 32
Apparent Clearance (CL/F) of BIIB059	For SC cohorts only	Up to Week 32
Volume of Distribution (Vss) of BIIB059		Up to Week 32
Apparent Volume of Distribution (Vz/F) of BIIB059	For SC cohorts only	Up to Week 32
Bioavailability (F) for a single SC dose of BIIB059		Up to Week 32
Absorption Rate Profile for a Single SC Dose of BIIB059		Up to Week 32
Number of Participants Who Develop Serum Anti-BIIB059 Antibodies		Up to Week 32

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2014
• Primary Completion (Actual): May 24, 2016
• Study Completion (Actual): May 24, 2016

Study Registration Dates

• First Submitted: April 4, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 8, 2014

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 230LE101; 2013-005361-39 (EudraCT Number)