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

NCT ID: NCT02106897

Last Updated: 2023-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-05-24

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.

Conditions

Systemic Lupus Erythematosus; Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1, Cohort 1: BIIB059 0.05 mg/kg IV

BIIB059 0.05 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 2: BIIB059 0.3 mg/kg IV

BIIB059 0.3 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 3: BIIB059 1 mg/kg IV

BIIB059 1 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 4: BIIB059 3 mg/kg IV

BIIB059 3 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 5: BIIB059 10 mg/kg IV

BIIB059 10 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 6: BIIB059 20 mg/kg IV

BIIB059 20 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 7: BIIB059 50 mg SC

BIIB059 50 mg SC dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 1-6: Placebo IV

Matching placebo IV dose, Once on Day 1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See Arm Descriptions

Part 1, Cohort 7: Placebo SC

Matching placebo SC dose, Once on Day 1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See Arm Descriptions

Part 2, Cohort 8: BIIB059 20 mg/kg IV

BIIB059 20 mg/kg IV dose, Once on Day 1

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 2, Cohort 8: Placebo IV

Matching placebo IV dose, Once on Day 1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See Arm Descriptions

Part 3a, Cohort 9: BIIB059 20 mg SC

BIIB059 20 mg SC dose, Every 4 weeks for 2 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3a, Cohort 10: BIIB059 50 mg SC

BIIB059 50 mg SC dose, Every 4 weeks for 2 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3a, Cohort 11: BIIB059 150 mg SC

BIIB059 150 mg SC dose, Every 4 weeks for 2 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3a, Cohort 12: BIIB059 300 mg or less SC

BIIB059 300 mg or less SC dose, Every 2 weeks for 3 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3a, Cohort 9-12: Placebo SC

Matching placebo SC dose, Every 4 weeks for 2 doses or every 2 weeks for 3 doses

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See Arm Descriptions

Part 3b, Cohort 13: BIIB059 50 mg SC

BIIB059 50 mg SC dose, Every 4 weeks for 2 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3b, Cohort 14: BIIB059 300 mg or less SC

BIIB059 300 mg or less SC dose, Every 2 weeks for 3 doses

Group Type: EXPERIMENTAL

BIIB059 (litifilimab)

Intervention Type: DRUG

See Arm Descriptions

Part 3b, Cohort 13-14: Placebo SC

Matching placebo SC dose, Every 4 weeks for 2 doses or every 2 weeks for 3 doses

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

See Arm Descriptions

Interventions

BIIB059 (litifilimab)

See Arm Descriptions

Intervention Type: DRUG

Placebo

See Arm Descriptions

Intervention Type: DRUG

Other Intervention Names

litifilimab

Eligibility Criteria

Inclusion Criteria

• 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.

• 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.

• 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.

• 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.

Exclusion Criteria

• 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

• 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.

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

Research Site

Anniston, Alabama, United States

Research Site

Birmingham, Alabama, United States

Research Site

Orlando, Florida, United States

Research Site

Great Neck, New York, United States

Research Site

Duncansville, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30645203 (View on PubMed)

Other Identifiers

2013-005361-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

230LE101

Identifier Type: -

Identifier Source: org_study_id