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

Study Overview
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Brief Summary
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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).

Official Title
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A 2-Part Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of BIIB059 in Subjects With Systemic Lupus Erythematosus and Active Skin Manifestations and in Subjects With Active Cutaneous Lupus Erythematosus With or Without Systemic Manifestations

Conditions
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Systemic Lupus Erythematosus, Active Cutaneous Lupus Erythematosus

Intervention / Treatment
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* Drug: BIIB059 (litifilimab)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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: 1. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: BIIB059 450 mg<br>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. | Drug: BIIB059 (litifilimab)<br>* Administered as specified in the treatment arm.<br>* Other names: litifilimab;|
| Placebo Comparator: Part A: Placebo<br>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. | Drug: Placebo<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Part B: BIIB059 50 mg<br>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. | Drug: BIIB059 (litifilimab)<br>* Administered as specified in the treatment arm.<br>* Other names: litifilimab;|
| Experimental: Part B: BIIB059 150 mg<br>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. | Drug: BIIB059 (litifilimab)<br>* Administered as specified in the treatment arm.<br>* Other names: litifilimab;|
| Experimental: Part B: BIIB059 450 mg<br>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. | Drug: BIIB059 (litifilimab)<br>* Administered as specified in the treatment arm.<br>* Other names: litifilimab;|
| Placebo Comparator: Part B: Placebo<br>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. | Drug: Placebo<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change From Baseline in Active Joint Count (28-joint Assessment) 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. | Baseline to Week 24 | 
| Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score 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. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A : Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at 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. | Week 24 | 
| Part B: Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity- 50 (CLASI-50) Response at Week 12 and 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. | Week 12, 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 | 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. | Baseline, Week 12, 16 and 24 | 
| Part B: Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at 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. | Baseline, Week 12 | 
| 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 | 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. | Week 24 | 
| 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 | 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. | Week 12, Week 16 | 
| 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 | 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. | Week 24 | 
| 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 | 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. | Week 12, Week 16 | 
| Part A: Percentage of Participants Achieving a Systemic Lupus Erythematosus (SLE) Responder Index >=4 (SRI-4) at 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. | Week 24 | 
| Part A: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at 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. | Baseline to Week 24 | 
| Part A: Percentage of Participants With no New Organ System Affected at 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. | Week 24 | 
| Part A: Change From Baseline in Physician's Global Assessment (PGA) of SLE Visual Analog Scale (VAS) Score at 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. | Baseline to Week 24 | 
| Part A: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline up to Week 36 | 
| Part B: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline up to Week 28 | 
| Part A: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities |  | Baseline up to Week 36 | 
| Part B: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities |  | Baseline up to Week 28 | 
| 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 A: Number of Participants With Clinically Significant 12-Lead Electrocardiograms (ECGs) 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: Number of Participants With Positive BIIB059 Antibodies |  | Baseline up to Week 24 | 
| Part B: Number of Participants With Positive BIIB059 Antibodies |  | Baseline up to Week 16 | 
| Part A: Absolute Change From Baseline Over Time in Immunoglobulin Levels |  | Baseline up to Week 24 | 
| 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 | Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) were analyzed, including 23 types of serotypes (sero). AB = Antibody. | Baseline to Week 24 | 
| Part B: Absolute Change From Baseline in Vaccine Titers - Streptococcus Pneumoniae (S. Pneumoniae) at Week 12 | Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) were analyzed, including 23 types of serotypes (sero). AB = Antibody. | Baseline to Week 12 | 
| Part A: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 24 | Vaccine-related immunoglobulin titers for tetanus and diphtheria were analyzed using international units per milliliter (IU/mL). | Baseline to Week 24 | 
| Part B: Absolute Change From Baseline in Vaccine Titers - Clostridium Tetani (C. Tetani) and Diphtheria at Week 12 | Vaccine-related immunoglobulin titers for tetanus and diphtheria were analyzed. | Baseline to Week 12 | 
| Part A: Percent Change From Baseline Over Time in Immunoglobulin Levels |  | Baseline up to Week 24 | 
| Part B: Percent Change From Baseline Over Time in Immunoglobulin Levels |  | Baseline up to Week 16 | 
| Part A: Percent Change From Baseline in Vaccine Titers at Week 24 | Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) including 23 types of serotypes (sero), tetanus and diphtheria were analyzed. AB = Antibody | Baseline to Week 24 | 
| Part B: Percent Change From Baseline in Vaccine Titers at Week 12 | Vaccine-related immunoglobulin (Ig) titers for Pneumococcus (S. pneumoniae) including 23 types of serotypes (sero), tetanus and diphtheria were analyzed. AB = Antibody. | Baseline to Week 12 | 
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLE, SLE, Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus