Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN)

Study Overview
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Brief Summary
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Phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of daxdilimab in patients with active, proliferative lupus nephritis (LN).

Detailed Description
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Approximately 210 participants will be randomized to receive daxdilimab or placebo administered subcutaneously through Week 52 in addition to their standard of care background therapy (mycophenolate mofetil (MMF) and corticosteroids). At Week 64, all participants will be assigned to a quarterly dosing maintenance regimen of either daxdilimab or placebo based upon pre-defined renal response observed by Week 52. The maximum trial duration per participant is approximately 116 weeks including a 4-week screening period, the 104 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
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy and Safety of Daxdilimab in Adult Participants With Active Proliferative Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Daxdilimab
* Drug: Daxdilimab
* Drug: Placebo (Normal Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to understand and provide written informed consent Adult men or women 18 to 80 years of age Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus (SLE) Have at least one of the following at Screening per central lab: Antinuclear antibodies (ANA) ≥ 1:80 Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results) Anti-Smith antibodies elevated to above normal (ie, positive results). Diagnosis of proliferative LN based on a renal biopsy obtained within 6 months prior to signing the informed consent form (ICF) or during the Screening Period: Class III (± class V) or class IV (± class V) LN according to the World Health Organization (WHO) or 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification (based on local evaluation of renal biopsy). Urine protein to creatinine ratio ≥113.17 mg/mmol, obtained via a 24-hour urine collection at Screening. Estimated glomerular filtration rate ≥35 mL/min/1.73 m2 Negative serum beta-human chorionic gonadotropin test at Screening (females of childbearing potential only). Key Exclusion Criteria: History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the investigational product or to a previous monoclonal antibody or human immunoglobulin therapy. Known intolerance to ≤1.0 gm/day of MMF or equivalent dose of mycophenolic acid (MPA). A diagnosis of pure Class V membranous LN based on a renal biopsy obtained within 6 months prior to signing ICF or during the Screening Period. History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 12-month period after enrollment. History of, or current renal diseases (other than LN) that in the opinion of the Investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy). Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection per central laboratory, splenectomy, or any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection. Hepatitis B, Hepatitis C, active tuberculosis (TB), any severe herpes infection, clinically active infection, or opportunistic infection. Clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization. History of cancer within the past 5 years, except in situ carcinoma of the cervix, cutaneous basal cell or squamous cell carcinoma with curative therapy. Receipt of a live vaccine within 4 weeks prior to Day 1. The use of immunosuppressants, biologics, and DMARDS within the protocol defined washout periods.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Daxdilimab Arm 1<br>Daxdilimab injections over a total of 104 weeks | Drug: Daxdilimab<br>* Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734<br>|
| Experimental: Daxdilimab Arm 2<br>Daxdilimab injections over a total of 104 weeks | Drug: Daxdilimab<br>* Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734<br>|
| Placebo Comparator: Placebo<br>Placebo injections over a total of 104 weeks | Drug: Placebo (Normal Saline)<br>* Placebo will be administered subcutaneously as two injections for each dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving complete renal response (CRR) at Week 48 and sustained through Week 52. |  | Week 48 to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving overall renal response (ORR) at Week 48 and sustained through Week 52. |  | Week 48 to Week 52 | 
| Change from baseline in estimated glomerular filtration rate (eGFR) at Week 52. |  | Day 1 to Week 52 | 
| Proportion of participants able to taper oral corticosteroids (OCS) to target by Week 24 and maintain target dose through Week 52. |  | Week 24 to Week 52 | 
| Anti-Drug Antibody (ADA) rate. |  | Day 1 to Week 116 | 
| Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent adverse events of special interest (AESIs). |  | Day 1 to Week 116 |