Chronic Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus
Conditions
Keywords
Cutaneous Lupus Erythematosus (CLE), Discoid Lupus Erythematosus (DLE), Systemic Lupus Erythematosus (SLE), Lupus, Subacute Cutaneous Lupus Erythematosus (SCLE)
Brief summary
In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue. The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the skin disease. Researchers will measure symptoms and signs of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI). The main questions researchers want to answer are: * How many participants have a score of 0 or 1 on the CLA-IGA-R looking at skin redness after treatment? * How many participants have their skin disease activity go down by at least 70% as measured by CLASI? Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and CLE have on the quality of life of participants using a group of questionnaires. The study will be split into 2 parts - Part A and Part B. Both parts will be done as follows: * After screening, participants will be randomized to receive either litifilimab or placebo for the 1st treatment period. A placebo looks like the study drug but contains no real medicine. * Participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks. * The 1st treatment period will be double blinded which means neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo. * This double blinded treatment period will last 24 weeks, after which the 2nd treatment period will begin. * During the 2nd treatment period, all participants will receive litifilimab for 28 weeks. * After completing treatment in this study, participants that qualify will be given the choice to join the Long-Term Extension study, 230LE305. If they do not, they will move into a follow-up safety period that will last up to 24 weeks. * The total study duration for participants will be up to 80 weeks.
Detailed description
Litifilimab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting blood dendritic cell antigen 2. It is an inhibitory receptor expressed on the surface of human plasmacytoid dendritic cell (pDCs) and is being investigated for the potential treatment of systemic lupus erythematosus and cutaneous lupus erythematosus. The primary objectives of the study are to evaluate the efficacy of litifilimab compared with placebo in reducing skin disease activity measured by the CLA-IGA-R score \[Parts A\] and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score \[Part B\] in participants with active SCLE and/or CCLE with or without systemic manifestations and refractory and/or intolerant to antimalarials. The secondary objectives of the study are to evaluate the efficacy of litifilimab in reducing SCLE and/or CCLE disease activity by CLA-IGA-R, CLASI-A; to evaluate additional efficacy parameters of litifilimab in reducing SCLE and/or CCLE disease activity; safety; tolerability; and immunogenicity of litifilimab \[Parts A and B\].
Interventions
DRUGLitifilimab
Administered as specified in the treatment arm.
DRUGPlacebo
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Histologically confirmed (in the past or during the Screening period) diagnosis of CLE with or without systemic manifestations. 2. Must have active cutaneous manifestations that meet study criteria. 3. Must have a CLASI-A score ≥10. 4. Must have an active CLE lesion despite an adequate trial of antimalarial treatment. Key
Exclusion criteria
1. Any active skin conditions other than CLE that may interfere with the study assessments of CLE. 2. Diagnosis of mixed connective tissue disease \[(within 1 year of signing the informed consent form (ICF)\] or any history of overlap syndromes of SLE including concomitant presence with rheumatoid arthritis, dermatomyositis and/or polymyositis, systemic sclerosis, psoriatic arthritis, or any other autoimmune disease that may confound the evaluation of the disease activity or the effect of the investigational product. Exceptions for overlap syndrome of SLE include participants with overlap syndrome of SLE with myositis and secondary Sjögren's syndrome at screening is permitted provided the participant also meets the criteria for classification as SLE. A past history of mixed connective tissue disease that over time has developed into a diagnosis of SLE is permitted, provided diagnosis of SLE has been present for at least 1 year. 3. Active severe lupus nephritis. 4. Active neuropsychiatric SLE. 5. Use of intralesional corticosteroids within 1 week prior to Screening and during the study. 6. Use of immunosuppressive or disease-modifying treatments for SLE or CLE \[via an oral, intravenous (IV), or SC route\] that were initiated less than 12 weeks prior to screening, have not been at a stable and allowable dose. NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts A: Percentage of Participants who Achieve a Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) Erythema Score of 0 or 1 | Week 16 |
| Part B: Percentage of Participants who Achieve Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI-70) Response, Defined as ≥ 70% Decrease in CLASI-A Score From Baseline | Baseline to Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Part A: Percentage of Participants With a CLASI-70 Response at Week 52 Among CLASI-70 Responders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Litifilimab During the DBPC Treatment Period (TP) | Week 52 |
| Part A: Percentage of Participants With CLA-IGA-R Erythema Score of 0 or 1 at Week 52 Among CLA-IGA-R Erythema Responders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part A: Percentage of Participants With CLA-IGA-R OMC Score of 0 or 1 and at Least 1 Level of Improvement From Baseline at Week 52 Among CLA-IGA-R OMC Responders at Weeks 16 &24, Respectively, who Were Assigned to Receive Litifilimab in DBPC TP | Week 52 |
| Part A: Percentage of Participants With CLA-IGA-R OMC Score of 0 at Week 52 Among CLA-IGA-R OMC Responders With CLA-IGA-R OMC Score of 0 at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Litifilimab During DBPC TP | Week 52 |
| Part A: Percentage of Participants With CLA-IGA-R Follicular Activity Score of 0 at Week 52 Among CLA-IGA-R Follicular Activity Responders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Litifilimab in DBPC TP | Week 52 |
| Part A: Percentage of Participants With a CLASI-70 Response at Week 52 Among CLASI-70 Nonresponders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Placebo During the DBPC TP | Week 52 |
| Part A: Percentage of Participants With a CLA-IGA-R Erythema Score of 0 or 1 at Week 52 Among CLA-IGA-R Erythema Nonresponders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Placebo During the DBPC TP | Week 52 |
| Part A: Percentage of Participants With CLA-IGA-R OMC Score of 0 or 1 and at Least 1 Level of Improvement From Baseline at Week 52 Among CLA-IGA-R OMC Nonresponders at Weeks 16 and 24, Respectively, who Were Assigned to Receive Placebo in DBPC TP | Week 52 |
| Part A: Percentage of Participants With a CLA-IGA-R OMC Score of 0 at Week 52 Among CLA-IGA-R OMC Nonresponders at Week 16 and Week 24, Respectively, who Were Randomly Assigned to Receive Placebo During the DBPC TP | Week 52 |
| Part A: Percentage of Participants who Have CLA-IGA-R Follicular Activity Score of 0 at Week 52 Among CLA-IGA-R Follicular Activity Nonresponders at Weeks 16 and 24, Respectively, who Were Randomly Assigned to Receive Placebo in DBPC TP | Week 52 |
| Part A: Annualized Mild and Moderate SFI Rate and Annualized Severe SFI Rate Through Week 16 | Up to Week 16 |
| Part A: Absolute Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index Damage (CLASI-D) Score at Week 52 | Baseline to Week 52 |
| Part A: Percent Change in CLASI-D Score | Baseline to Week 52 |
| Part B: Percentage of Participants who Achieve a CLASI A score of 0 to 3 | Week 24 |
| Part B: Percentage of Participants who Achieve a CLA-IGA-R OMC Score of 0 or 1 and at Least 2-Point Improvement From Baseline at Week 24, for Participants who had CLA-IGA-R OMC Score ≥ 2 at Baseline | Week 24 |
| Part B: Percentage of Participants who Achieve a CLA-IGA-R Erythema Score of 0 or 1, at Week 16 and Week 24, Respectively, for Participants in Full Analysis Set (FAS), who had CLA-IGA-R Erythema Score ≥3 and Other OMC Score ≥3 at Baseline | Weeks 16 and 24 |
| Part B: Percentage of Participants who Achieve a CLA-IGA-R OMC Score of 0 or 1, at Week 16 and Week 24, Respectively, for Participants in FAS, who had CLA-IGA-R Erythema Score ≥3 and OMC Score ≥3 at Baseline | Weeks 16 and 24 |
| Part B: Percentage of Participants who Achieve CLA IGA R Erythema Score of 0 or 1 | Up to Week 24 |
| Part B: Percentage of Participants who Achieve at Least 1 Level of Improvement From Baseline in the CLA-IGA-R Erythema Score | Up to Week 24 |
| Part B: Percentage of Participants who Achieve a CLASI-A Score of 0 to 5 | Up to Week 24 |
| Part B: Percentage of Participants who Achieve a CLASI-50a Response, Defined as a ≥ 50% Decrease in Baseline CLASI-A Score in Addition to Achieving Mild Disease Severity With a CLASI-A Score <10 at Week 16 and Week 24, Respectively | Weeks 16 and 24 |
| Part B: Percentage of Participants With a CLASI 70 Response at Week 52 Among CLASI-70 Responders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLASI 50 Response at Week 52 Among CLASI-50 Responders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLASI A 0 to 3 Response at Week 52 Among CLASI-A 0 to 3 Responders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA R Erythema Score of 0 or 1 at Week 52 Among CLA-IGA-R Erythema Responders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA R OMC score of 0 at Week 52 Among CLA IGA R OMC Responders With a CLA-IGA-R OMC Score of 0 at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA-R Follicular Activity Score of 0 at Week 52 Among CLA-IGA-R Follicular Activity Responders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLASI 70 Response at Week 52 Among CLASI-70 Nonresponders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLASI 50 Response at Week 52 Among CLASI-50 Nonresponders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLASI A 0 to 3 Response at Week 52 Among CLASI-A 0 to 3 Nonresponders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA R Erythema Score of 0 or 1 at Week 52 Among CLA-IGA-R Erythema Nonresponders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA R OMC score of 0 at Week 52 Among CLA IGA R OMC Nonresponders With a CLA-IGA-R OMC Score of 0 at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Percentage of Participants With a CLA IGA-R Follicular Activity Score of 0 at Week 52 Among CLA-IGA-R Follicular Activity Nonresponders at Week 24, who Were Randomly Assigned to Receive Litifilimab During the DBPC TP | Week 52 |
| Part B: Absolute Change in CLASI-D Score | Week 52 |
| Part B: Percent Change in CLASI-D Score | Week 52 |
| Part B: Change From Baseline in Cutaneous Lupus Erythematosus-Quality of Life (CLE-QoL) Score | Part B: Weeks 16, 24 and 52 |
| Part B: Change From Baseline in Dermatology Life Quality Index (DLQI) Score | Part B: Weeks 16, 24 and 52 |
| Part B: Change From Baseline in Numerical Rating Scale (NRS) for Pain in Skin Rash | Part B: Weeks 16, 24 and 52 |
| Part B: Change From Baseline in NRS for Itch in Skin Rash | Part B: Weeks 16, 24 and 52 |
| Parts A and B: Percentage of Participants who Achieve a CLA-IGA-R Erythema Score of 0 or 1 | Part A: Week 24; Part B: Weeks 16 and 24 |
| Parts A and B: Percentage of Participants who Achieve a CLA-IGA-R Other Morphologic Characteristics (OMC) Score of 0 or 1 and at Least 1 Level of Improvement From Baseline | Part A: Weeks 16 and 24; Part B: Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a CLA-IGA-R OMC Score of 0 | Part A: Weeks 16 and 24; Part B: Up to Week 24 |
| Parts A and B: Percentage of Participants With at Least 1 Level of Improvement From Baseline in CLA-IGA-R OMC Score | Part A: Weeks 16 and 24; Part B: Up to Week 24 |
| Parts A and B: Percentage of Participants who Have a CLA-IGA-R Follicular Activity Score of 0 | Part A: Weeks 16 and 24; Part B: Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a CLASI-70 Response, Defined as a ≥ 70% Decrease in CLASI-A Score From Baseline | Parts A: Weeks 16 and 24; Part B: Week 12 |
| Parts A and B: Percentage of Participants who Achieve a CLASI-50 Response, Defined as a ≥ 50% Decrease in CLASI-A Score From Baseline | Part A: Weeks 16 and 24; Part B: Weeks 12 and 24 |
| Parts A and B: Percentage of Participants who Achieve a CLASI-A Score of 0 or 1 | Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a CLASI-A Score of 0 to 3 | Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a CLASI 70 Response | Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a CLASI 50 Response | Up to Week 24 |
| Parts A and B: Percentage of Participants who Achieve a 7-Point Reduction From Baseline in CLASI-A Score | Up to Week 24 |
| Parts A and B: Annualized Mild and Moderate Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index Flare Index Rate and Annualized Severe SFI Rate Through Week 24 | Up to Week 24 |
| Parts A and B: Annualized Mild and Moderate SFI Rate and Annualized Severe SFI Rate Through Week 52 | Up to Week 52 |
| Parts A and B: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Week 76 |
| Parts A and B: Number of Participants With Anti-Litifilimab Antibodies in Serum During the Study | Up to Week 76 |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, France, Germany, Hungary, Italy, Japan, Mexico, Peru, Philippines, Poland, Portugal, Puerto Rico, Saudi Arabia, Serbia, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed