Study of Daxdilimab (HZN-7734) in Patients With Moderate-to-Severe Primary Discoid Lupus Erythematosus

Study Overview
=================
Brief Summary
-----------------
A Phase 2, double-blind, randomized, placebo-controlled parallel-group study to evaluate the efficacy and safety of daxdilimab in participants with moderate-to-severe active primary Discoid Lupus Erythematosus (DLE) refractory to standard of care.

Detailed Description
-----------------
Approximately 99 participants will be enrolled to receive daxdilimab or placebo administered subcutaneously once every four weeks (Q4W) from Day 1 to Week 44. After week 24 all subjects will be receiving daxbilimab, including those assigned to the placebo arm, Q4W from Week 24 to Week 44. The maximum trial duration per participant is approximately 60 weeks including screening, the 48 weeks for the treatment period where participants will receive daxdilimab or placebo, and approximately 8 weeks for the follow-up period. Safety evaluations will be performed regularly throughout the course of the study.

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Investigate the Efficacy and Safety of Daxdilimab Subcutaneous Injection in Reducing Disease Activity in Adult Participants With Moderate-to-Severe Primary Discoid Lupus Erythematosus

Conditions
-----------------
Discoid Lupus Erythematosus

Intervention / Treatment
-----------------
* Drug: Placebo/Daxdilimab
* Drug: Daxdilimab
* Drug: Daxdilimab


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Willing and able to understand and provide written informed consent. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. A diagnosis of discoid lupus erythematosus for ≥ 6 months prior to screening supported by a history of: A biopsy or a clinical feature score of ≥ 7 on the DLE Classification Criteria (DLECC) scale Currently active discoid lupus with all the following Digital photography adjudicated with central reading to confirm a currently active discoid disease lesion. CLASI-A score ≥ 8 related to discoid lesions at Baseline Treatment refractory DLE defined as active disease despite current or historical treatment with a systemic treatment. Females are eligible to participate if they are not pregnant or breastfeeding, and meet the contraceptive/barrier requirement(s). Males are eligible to participate if they agree to the contraceptive/barrier requirement(s). Vaccination status should be up to date per local standards. Key Exclusion Criteria: Participation in another clinical study with an investigational drug within 4 weeks prior to Randomization or within 5 published half-lives, whichever is longer. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product (IP) or interpretation of participant safety or trial results. Weight > 160 kg (352 pounds) at Screening. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous monoclonal antibody (mAb) or human immunoglobin (Ig) therapy. Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the informed consent form (ICF) through 6 months after receiving the last dose of IP. Splenectomy Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to screening through randomization. History of clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization; arrhythmia requiring active therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities. History of cancer within the past 5 years, except as follows: In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to Screening, or Cutaneous basal cell or squamous cell carcinoma treated with curative therapy. Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection. Known history of a primary immunodeficiency or an underlying condition, such as known human immunodeficiency virus (HIV) infection, or a positive result for HIV infection per central laboratory. Participants with positive hepatitis B serologic test results. All participants will undergo testing for hepatitis C antibody (HCVAb) during Screening. Participants who are HCVAb positive will be reflex tested for hepatitis C virus (HCV) RNA and if HCV RNA is positive, the participant is not eligible for the study. Active tuberculosis (TB), or a positive interferon-gamma release assay (IGRA) test at screening, unless documented history of appropriate treatment for active or latent TB. Participants with an indeterminate IGRA test result can repeat the test, but if the repeat test is also indeterminate, they will be excluded. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus (CMV)) at any time prior to Randomization, including, but not limited to, disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the last 2 years), or ophthalmic herpes. Any herpes zoster, cytomegalovirus (CMV), or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to Randomization. Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 2 years prior to Randomization. Any acute illness or evidence of clinically significant active infection on Day 1. Participants who have COVID-19 or other significant infection, or in the judgment of the Investigator, may be at a high risk of COVID-19 or its complications should not be randomized. Systemic lupus erythematosus defined by fulfilling 2020 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for systemic lupus erythematosus (SLE). Current diagnosis of a systemic connective tissue disease. Current inflammatory skin disease other than DLE, that, in the opinion of the Investigator, could interfere with the inflammatory skin assessments and confound the disease activity assessments. Exposure to an experimental drug either 30 days, 5 half-lives of the agent, or twice the duration of the biological effect of the agent, whichever is longer, prior to Randomization and through the final trial visit. Receipt of a live-attenuated vaccine within 4 weeks prior to Randomization.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo/Daxdilimab Arm 1<br>Administration of placebo Q4W from Day 1 through Week 20 and administration of Daxdilimab Q4W from Week 24 through Week 44. | Drug: Placebo/Daxdilimab<br>* Placebo/Daxdilimab will be administered subcutaneously as two injections for each dose.<br>|
| Experimental: Daxdilimab Arm 2<br>Administration of Daxdilimab Q4W from Day 1 through Week 44. | Drug: Daxdilimab<br>* Daxdilimab will be administered subcutaneously as two injections for each dose.<br>* Other names: HZN-7734;|
| Experimental: Daxdilimab Arm 3<br>Administration of Daxdilimab Q4W from Day 1 through Week 44. | Drug: Daxdilimab<br>* Daxdilimab will be administered subcutaneously as two injections for each dose.<br>* Other names: HZN-7734;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in Cutaneous Lupus Erythematosus Disease and Severity Index-Activity (CLASI-A) score from Baseline to Week 24. |  | Day 1 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve 0 or 1 on the Cutaneous Lupus Activity-Investigator's Global Assessment (CLA-IGA) scale at Week 24 (5-point Likert scale [0-4]). |  | Day 1 to Week 24 | 
| Proportion of participants who achieve a ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease and Severity Index-Activity (CLASI-A) score from Baseline (Day 1) at Week 24. |  | Day 1 to Week 24 | 
| Mean change in the Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE) from Baseline (Day 1) to Week 24 patients with primary DLE. |  | Day 1 to Week 24 | 
| Serum concentration of daxdilimab over time. |  | Day 1 to Week 48 | 
| Anti-Drug Antibody (ADA) rate. |  | Day 1 to Week 56 | 
| Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (TEAESIs). |  | Day 1 to Week 56 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Discoid Lupus Erythematosus, Immune System Diseases, Lupus Erythematosus, Cutaneous, Skin Diseases, Connective Tissue Diseases