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

• Sponsor: Biogen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02106897
• Collaborator: (none)
• Enrollment: 109
• Locations: 5
• Arms: 19
• Actual Duration (Months): 24.8
• Patients Per Site: 21.8
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus; Healthy Volunteers	Drug: BIIB059; Drug: Placebo	Phase 1

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Single-Ascending-Dose and Multiple-Ascending-Dose Study of BIIB059 in Healthy Volunteers and Subjects With Systemic Lupus Erythematosus
• Actual Study Start Date: Apr 30, 2014
• Actual Primary Completion Date: May 24, 2016
• Actual Study Completion Date: May 24, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants that Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 32]

Secondary Outcome Measures

1. Area Under the Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of BIIB059 [Up to Week 32]

2. Maximum Observed Concentration (Cmax) of BIIB059 [Up to Week 32]

3. Time to Reach Maximum Observed Concentration (Tmax) of BIIB059 [Up to Week 32]

4. Terminal Elimination Half-Life (t1/2) of BIIB059 [Up to Week 32]

5. Clearance (CL) of BIIB059 [Up to Week 32]

6. Apparent Clearance (CL/F) of BIIB059 [Up to Week 32]

   For SC cohorts only

7. Volume of Distribution (Vss) of BIIB059 [Up to Week 32]

8. Apparent Volume of Distribution (Vz/F) of BIIB059 [Up to Week 32]

   For SC cohorts only

9. Bioavailability (F) for a single SC dose of BIIB059 [Up to Week 32]

10. Absorption Rate Profile for a Single SC Dose of BIIB059 [Up to Week 32]

11. Number of Participants Who Develop Serum Anti-BIIB059 Antibodies [Up to Week 32]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anniston	Alabama	United States	36207
2	Research Site	Birmingham	Alabama	United States	35294
3	Research Site	Orlando	Florida	United States	32806
4	Research Site	Great Neck	New York	United States	11021
5	Research Site	Duncansville	Pennsylvania	United States	16635

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: NCT02106897
• Other Study ID Numbers: 230LE101; 2013-005361-39
• First Posted: Apr 8, 2014
• Last Update Posted: Oct 26, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

No Results Posted as of Oct 26, 2017