A Study of DS-7011a in Patients With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus

Study Overview
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Brief Summary
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Systemic lupus erythematosus (SLE) is a systemic chronic autoimmune disease characterized by autoantibody production, inflammation, and tissue damage in multiple organs. Standard of care therapies used to treat SLE are only partially effective and have a wide range of toxicities. There is a need for more effective and safer therapies for patients with SLE.

Detailed Description
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This Phase 1b/2 study will initially explore the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of DS-7011a in patients with SLE and active cutaneous lupus erythematosus (CLE). DS-7011a is an anti-Toll-like receptor 7 (TLR7) antagonistic monoclonal antibody developed for the treatment of SLE.

Official Title
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A Phase 1b/2, Double-Blind, Placebo-Controlled, Randomized, Parallel-Arm Study to Explore the Safety, Pharmacokinetics, and Proof of Biological Activity of DS-7011a in Patients With Systemic Lupus Erythematosus and Active Cutaneous Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus

Intervention / Treatment
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* Drug: DS-7011a
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants must be of 18 years or more with definite SLE for at least 6 months prior to Screening, defined according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, including documented history of positivity for antinuclear antibody (titer ≥1:80). Body mass index (BMI) 18 to 40 kg/m^2 inclusive and body weight ≥45 kg. Presence of active CLE (acute, subacute, and chronic cutaneous lupus), with active skin involvement and a CLASI-A score of 4 or higher at the time of screening and randomization adjudicated by 2 dermatologists, despite adequate use of conventional therapies (either topical corticosteroids or antimalarial agents used for at least 12 weeks prior to Screening) or because of the requirement to discontinue these therapies due to side effects or poor tolerability. Participants must be willing to have skin tape harvests collected from the affected skin area (skin tape stripping done on the target lesion). Participants must agree not to participate in any other investigational study during the study Treatment Period and for 3 months after the last dose of study drug. Participants must give written informed consent to participation in the study prior to Screening. Participants must be vaccinated and boosted against COVID-19, i.e., must have received all recommended primary vaccination doses and at least one booster dose, if eligible. Exclusion Criteria: Active lupus nephritis (LN) on induction therapy, or induction therapy completed within 12 weeks prior to Screening (stable maintenance therapy with mycophenolate or azathioprine allowed). 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. Primary diagnosis of autoimmune or rheumatic disease other than SLE (secondary Sjögren's syndrome or autoimmune thyroiditis are not exclusionary) or drug-induced lupus. History of chronic, recurrent (3 or more of the same type of infection in 1 year) or recent serious infection, including viral infections, as determined by the investigator, or requiring anti-infective treatment within 12 weeks prior to Screening. History of severe herpes infection or signs of herpes or varicella zoster viral infection within 12 weeks prior to Screening. Positive COVID-19 molecular test at Screening or symptoms suggestive of SARS-CoV-2 infection or close contact with an individual with SARS-CoV-2 infection within 2 weeks prior to randomization. History of, or ongoing, malignant disease except basal cell carcinomas and squamous cell carcinomas of the skin or carcinoma in situ of the cervix completely excised and considered cured for at least 2 years prior to Screening. Chronic kidney disease with significant proteinuria (ie, >2 g/24 h or urine protein to creatinine ratio >2) or decreased renal function (estimated glomerular filtration rate [eGFR] <30). New York Heart Association class III or IV congestive heart failure. Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study. History or positive test result for human immunodeficiency virus at Screening. Active hepatitis B virus infection determined as positive test result for hepatitis B surface antigen at Screening. Active hepatitis C virus (HCV) infection determined as HCV ribonucleic acid (RNA) above the limit of detection in subjects with positive HCV antibody titer, at Screening. History of, or ongoing, active tuberculosis (TB) or untreated latent TB infection (LTBI) at Screening. Participants with documented previously completed appropriate LTBI treatment and without evidence of re-exposure will not be required to be tested. Any other significant condition that according to the investigator's judgment would prevent compliance with study protocol and full study participation. Participants must not be participating in another investigational study or have participated in an investigational study within the past 30 days prior to randomization (Day 1). History of or current inflammatory skin disease other than SLE that in the opinion of the investigator could interfere with the inflammatory skin assessments and confound the disease activity assessments. History of any non-SLE disease that had required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 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: DS-7011a<br>Participants with systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) who will be randomized to receive DS-7011a 20 mg/kg every 4 weeks by intravenous infusion. | Drug: DS-7011a<br>* 20 mg/kg intravenous dose to be administered every 4 weeks at baseline (Day 1), Day 29, and Day 57<br>|
| Placebo Comparator: Placebo<br>Participants with systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) who will be randomized to receive placebo every 4 weeks by intravenous infusion. | Drug: Placebo<br>* Saline intravenous solution administered every 4 weeks at baseline (Day 1), Day 29, and Day 57<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events Following Administration with DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameter Area Under the Concentration Curve Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematous |  | Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113 | 
| Pharmacokinetic Parameter Maximum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematous |  | Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113 | 
| Pharmacokinetic Parameter Minimum Concentration Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus |  | Day 1 (at predose and at end of infusion), Day 2 (24 hours after administration), Day 8 (1 week after administration), Days 29 and 57 (at predose and at end of infusion), and Days 85 and 113 | 
| Change From Baseline in Cutaneous Lupus Area and Severity Index Activity Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 16 | 
| Change From Baseline in Cutaneous Lupus Activity Investigator Global Assessment Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 16 | 
| Change From Baseline in SLE Disease Activity Index 2000 Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 16 | 
| Change From Baseline in Clinician's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 16 | 
| Change From Baseline in Patient's Global Impression of Change Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus |  | Screening up to Week 16 | 
| Change From Baseline in Autoantibodies Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus | Autoantibodies, including antinuclear, anti-dsDNA, anti-Smith [Sm], and antiribonucleoprotein [RNP] antibodies, will be assessed. | Screening up to Week 16 | 
| Change From Baseline in Complement Factors Following Administration of DS-7011a in Participants With Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus | Complement factors, such as C3 and C4, will be assessed. | Screening up to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus, DS-7011a