Study to Evaluate BIIB059 (Litifilimab) in Cutaneous Lupus Erythematosus (CLE) With or Without Systemic Lupus Erythematosus (SLE)

Phase 2

Completed

Conditions: Systemic Lupus Erythematosus
Active Cutaneous Lupus Erythematosus

Interventions: Drug: BIIB059 (litifilimab)
Drug: Placebo

Registration Number: NCT02847598

Lead Sponsor: Biogen

Brief Summary: The primary purpose of the study is to evaluate the efficacy of BIIB059 (litifilimab) in reducing disease activity in participants with systemic lupus erythematosus (SLE) with active cutaneous manifestations and joint involvement (Part A), and in participants with active cutaneous lupus erythematosus (CLE) (Subacute cutaneous lupus erythematosus (SCLE) or chronic CLE, including discoid lupus erythematosus (DLE)) with or without systemic manifestations (Part B). The secondary objective is to evaluate additional efficacy parameters of BIIB059 in reducing SLE/CLE disease activity, pharmacokinetic parameters, safety and tolerability of BIIB059 (Parts A and B).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 264

Inclusion Criteria

Part A:

Diagnosis of systemic lupus erythematosus (SLE) fulfilling at least 4 out of 11 of the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE along with active skin manifestations and joint involvement.
At least 4 tender joints and at least 4 swollen joints with at least 4 of the swollen joints in the proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints and/or wrist.
Demonstrate at least one sign of active lupus skin disease, including acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and/or chronic cutaneous lupus erythematosus (CCLE) (e.g., discoid lupus erythematosus (DLE)), with skin activity defined by SLE Disease Activity Index 2000 (SLEDAI-2K) at the time of Screening and randomization.

Part B:

Active skin manifestations Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) ≥8)) and a diagnosis of cutaneous lupus erythematosus (CLE) that has been histologically confirmed (in the past or at Screening), with or without SLE manifestations.

Key

Exclusion Criteria

Active lupus nephritis or moderate-to-severe or chronic kidney disease.
Any active skin conditions other than CLE that may interfere with the study (e.g., psoriasis, non-LE skin lupus, drug-induced lupus).
History of chronic, recurrent (3 or more of the same type of infection in a 12-month period), or recent serious infection (e.g., pneumonia, septicemia, herpes zoster) as determined by the Investigator and requiring anti-infective treatment within 12 weeks prior to Screening.
Use of immunosuppressive or disease-modifying treatments for SLE or CLE that were initiated less than 12 weeks prior to Randomization.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: BIIB059 450 mg	BIIB059 (litifilimab)	BIIB059 450 mg administered SC, Q4W with an additional dose at Week 2 for a total of 7 doses (Weeks 0, 2, 4, 8, 12, 16, and 20) in participants with SLE with active skin manifestations and joint involvement.
Part B: Placebo	Placebo	BIIB059 matching placebo administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
Part A: Placebo	Placebo	BIIB059 matching placebo administered SC, Q4W with an additional dose at Week 2 for total of 7 doses (Weeks 0, 2, 4, 8, 12, 16, and 20) in participants with SLE with active skin manifestations and joint involvement.
Part B: BIIB059 50 mg	BIIB059 (litifilimab)	BIIB059 50 mg administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
Part B: BIIB059 450 mg	BIIB059 (litifilimab)	BIIB059 450 mg administered, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.
Part B: BIIB059 150 mg	BIIB059 (litifilimab)	BIIB059 150 mg administered SC, Q4W with an additional loading dose at Week 2 for a total of 5 doses (Weeks 0, 2, 4, 8, and 12) in participants with active CLE with or without systemic manifestations.

Primary Outcome Measures

Name	Time	Method
Part A: Change From Baseline in Active Joint Count (28-joint Assessment) to Week 24	Baseline to Week 24	An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). The 28 Joint Count includes assessment of swelling and tenderness in the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and knees. The investigator counts how many of the 28 joints are swollen or tender at the given week.
Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score to Week 16	Baseline to Week 16	The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a clinical tool that quantifies disease activity and damage in cutaneous lupus erythematosus (CLE). The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.

Secondary Outcome Measures

Name	Time	Method
Part B: Serum Concentration of BIIB059	Part B: pre-dose on Days 1, 29, 85 and post-dose on Days 1, 29, 85, 113, 141, 169 and 197
Part A: Percent Change From Baseline Over Time in Immunoglobulin Levels	Baseline up to Week 24
Part A: Absolute Change From Baseline Over Time in Immunoglobulin Levels	Baseline up to Week 24
Part A: Percentage of Participants With a >=4-point Reduction From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24	Week 24	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity. The percentage of participants with a \>=4-point reduction from baseline in CLASI-A score are reported here.
Part B: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16	Week 12, Week 16	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity. The percentage of participants with a \>=7-point reduction from baseline in CLASI-A score are reported here.
Part B: Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 12 and 16	Week 12, Week 16	CLASI-50 Response is defined as a 50% improvement from baseline in CLASI-A score at Weeks 12 and 16. The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.
Part A: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24	Baseline to Week 24	The SLEDAI-2K is a reliable, valid, simple, 1-page activity index that measures disease activity and records features of active lupus as present or not. It uses a weighted checklist to assign a numeric score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 28 days. Each symptom present is assigned between 1 and up to 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms), where higher scores representing increased disease activity.
Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12	Baseline, Week 12	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.
Part A: Percentage of Participants With a >=7-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 24	Week 24	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity. The percentage of participants with a \>=7-point reduction from baseline in CLASI-A score are reported here.
Part B: Percent Change From Baseline Over Time in Immunoglobulin Levels	Baseline up to Week 16
Part A: Percentage of Participants Achieving a Systemic Lupus Erythematosus (SLE) Responder Index >=4 (SRI-4) at Week 24	Week 24	An SRI-4 at Week 24 was a categorical response variable (Yes/No) incorporating the following criteria for achievement of responder status (i.e., all criteria must have been met to achieve responder status): A reduction from baseline of ≥4 points in SLEDAI-2K, No new organ system affected, as defined by no new BILAG-2004 Grade A and no more than 1 new BILAG-2004 Grade B, No worsening from baseline in participant's lupus disease activity, defined by a \<1-point increase in the PGA (VAS) \[on a scale of 0 to 10\],No changes to protocol-specified medication rules,as follows (all criteria were required to be met): No initiation or increase of SLE standard of care therapy or other disallowed concomitant therapy; Concomitant corticosteroid dosage at Week 24 to be ≤10 mg/day;Concomitant corticosteroid dosage at Week 24 was no more than at Day 1;No increase in corticosteroid dose between Weeks 17 and 24. The percentage of participants who had responded to each of the 4 criteria was also reported.
Part B: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities	Baseline up to Week 28
Part A : Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 24	Week 24	CLASI-50 Response is defined as a 50% improvement from baseline in CLASI-A score at Week 24. The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.
Part B: Percentage of Participants With a >=4-point Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 and 16	Week 12, Week 16	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity. The percentage of participants with a \>=4-point reduction from baseline in CLASI-A score are reported here.
Part B: Number of Participants With Positive BIIB059 Antibodies	Baseline up to Week 16
Part A: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12, 16 and 24	Baseline, Week 12, 16 and 24	The CLASI is a clinical tool that quantifies disease activity and damage in CLE. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Composite scores are calculated by summing the individual component scores. CLASI-A scores of 0-9, 10-20, and 21-70 represent disease severity of mild, moderate, and severe, respectively. Higher scores indicate more disease activity.
Part A: Percentage of Participants With no New Organ System Affected at Week 24	Week 24	No new organ system affected, as defined by no new British Isles Lupus Activity Group (BILAG)-2004 A and no more than one new BILAG-2004 B. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents very active disease, Grade B represents moderate disease activity, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. A score is applied to each grade of each organ system using coding scheme of A=12, B=8, C=1, and D/E=0 and is summarized as a total score ranging 0-108. Higher scores indicate more severe disease activity.
Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Week 36	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: Results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect.
Part B: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 12	Baseline to Week 12	Vaccine-related immunoglobulin titers for tetanus and diphtheria were analyzed.
Part A: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities	Baseline up to Week 36
Part A: Number of Participants With Positive BIIB059 Antibodies	Baseline up to Week 24
Part B: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 12	Baseline to Week 12	Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) were analyzed, including 23 types of serotypes (sero). AB = Antibody.
Part A: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 24	Baseline to Week 24	Vaccine-related immunoglobulin titers for tetanus and diphtheria were analyzed using international units per milliliter (IU/mL).
Part A: Serum Concentration of BIIB059	Part A: pre-dose on Days 1, 29, 85 and 113 and post-dose on Days 1, 8, 29, 85, 169, 197 and 253
Part A: Change From Baseline in Physician's Global Assessment (PGA) of SLE Visual Analog Scale (VAS) Score at Week 24	Baseline to Week 24	The PGA is used to quantify disease activity and is measured using an anchored VAS. The PGA asks the Investigator to assess the participants current disease activity from a score of 0 (none) to 3 (severe), where higher score means severe SLE disease activity.
Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Week 28	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: Results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect.
Part A: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities	Baseline up to Week 36
Part B: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) Abnormalities	Baseline up to Week 28
Part A: Percent Change From Baseline in Vaccine Titers at Week 24	Baseline to Week 24	Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) including 23 types of serotypes (sero), tetanus and diphtheria were analyzed. AB = Antibody
Part B: Percent Change From Baseline in Vaccine Titers at Week 12	Baseline to Week 12	Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) including 23 types of serotypes (sero), tetanus and diphtheria were analyzed. AB = Antibody.
Part A: Number of Participants With Clinically Significant Vital Sign Abnormalities	Baseline up to Week 36
Part B: Number of Participants With Clinically Significant Vital Sign Abnormalities	Baseline up to Week 28
Part B: Absolute Change From Baseline Over Time in Immunoglobulin Levels	Baseline up to Week 16
Part A: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 24	Baseline to Week 24	Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) were analyzed, including 23 types of serotypes (sero). AB = Antibody.

Trial Locations

Locations (54): TriWest Research Associates, LLC
🇺🇸
El Cajon, California, United States
Purushotham Akther & Rosan Kotha, MD Inc.
🇺🇸
La Mesa, California, United States
Pinnacle Research Group LLC
🇺🇸
Anniston, Alabama, United States
The Regents of the University of California
🇺🇸
La Jolla, California, United States
American Health Research, Inc.
🇺🇸
Charlotte, North Carolina, United States
Richard Barthel, MD
🇺🇸
Santa Barbara, California, United States
Inland Rheumatology Clinical Trials Inc.
🇺🇸
Upland, California, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Howard University Hospital
🇺🇸
Washington, District of Columbia, United States
Tien Q Nguyen MD Inc
🇺🇸
Fountain Valley, California, United States
MD Med Corp
🇺🇸
Hemet, California, United States
Universtiy of California, Irvine
🇺🇸
Irvine, California, United States
Dermatology Reserach Associates
🇺🇸
Los Angeles, California, United States
Robin K. Dore, MD, Inc.
🇺🇸
Tustin, California, United States
Lakes Research, LLC
🇺🇸
Miami Lakes, Florida, United States
Davis Group, LTD
🇺🇸
Las Vegas, Nevada, United States
Valley Hospital
🇺🇸
Ridgewood, New Jersey, United States
Medical Research Center Of Miami
🇺🇸
Miami, Florida, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸
Indianapolis, Indiana, United States
Ohio State University Clinical Trials
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburg Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC Arthritis Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Research Site
🇹🇭
Hat Yai, Songkhla, Thailand
Low Country Rheumatology, PA
🇺🇸
North Charleston, South Carolina, United States
University Clinical Trials
🇺🇸
San Diego, California, United States
Nazanin Firooz, MD Inc.
🇺🇸
West Hills, California, United States
Clinical Research of West Florida- Corporate
🇺🇸
Clearwater, Florida, United States
Washington DC VA Medical Center
🇺🇸
Washington, District of Columbia, United States
DMI Research, Inc.
🇺🇸
Pinellas Park, Florida, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Joint and Muscle Research Institute
🇺🇸
Charlotte, North Carolina, United States
Medication Management, LLC
🇺🇸
Greensboro, North Carolina, United States
PMG Research of Wilmington, LLC
🇺🇸
Wilmington, North Carolina, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸
Houston, Texas, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
Advanced Medical Reserarch, PC
🇺🇸
Sandy Springs, Georgia, United States
North Shore/Long Island Jewish PRIME
🇺🇸
Great Neck, New York, United States
Accurate Clinical Research, Inc.
🇺🇸
Houston, Texas, United States
Virginia Clinical Research
🇺🇸
Norfolk, Virginia, United States
Advanced Clinical Research
🇺🇸
Boise, Idaho, United States
Arizona Arthritis & Rheumatology
🇺🇸
Phoenix, Arizona, United States
Medical Faculty Associates, Inc.
🇺🇸
Washington, District of Columbia, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Univeristy of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Omega Research Consultants
🇺🇸
Orlando, Florida, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Austin Regional Clinic, P.A.
🇺🇸
Austin, Texas, United States
Albuquerque Center For Rheumatology
🇺🇸
Albuquerque, New Mexico, United States
Institute for Rheumatic & Autoimmune diseases, Overlook Medical Center
🇺🇸
Summit, New Jersey, United States
University of Tennessee Health Sciences Center
🇺🇸
Memphis, Tennessee, United States