A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients With Active Polymyositis or Dermatomyositis

Study Overview
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Brief Summary
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This is a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the safety, tolerability, efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of treatment with KZR-616 in patients with active Polymyositis (PM) or Dermatomyositis (DM). Patients will be evaluated for eligibility during the Screening Period. Eligible patients will be randomized 1:1 to Arm A or Arm B of the study. During the 32-week treatment period, patients will receive study drug subcutaneously (SC) once weekly with 2 treatment periods of 16 weeks each. This study will be conducted on an outpatient basis.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Active Polymyositis or Dermatomyositis

Conditions
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Polymyositis, Dermatomyositis

Intervention / Treatment
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* Drug: KZR-616
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients at least 18 years of age Body Mass Index (BMI) of 18 to 40 kg/m2 Diagnosis of probable or definite DM or PM Must confirm eligibility unless at least 1 of the following is present: Muscle biopsy with evidence of active myositis within the last 6 months prior to or at Screening Electromyography or magnetic resonance imaging with evidence of active myositis within the last 6 months prior to Screening A creatine kinase (CK) ≥4 × upper limit of normal (ULN). Must have demonstrable muscle weakness as measured by the Manual Muscle Testing-8 muscle Groups (MMT-8) with a score ≥80/150 but ≤136/150 units and any 2 of the following: Physician Global Assessment (MDGA) visual analog scale (VAS) ≥2 cm Patient Global Assessment of Disease Activity (PtGADA) VAS ≥2 cm At least one muscle enzyme laboratory measurement ≥1.3 × ULN Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS ≥1 cm. Documented inadequate response OR have demonstrated documented toxicity or intolerance to prior standard of care therapies Has had age-appropriate cancer screening that is up to date and negative for evidence of malignancy as per local standard of care Exclusion Criteria: Has significant muscle damage or has a muscle damage VAS score ≥5 cm on the MDI Any other form of myositis or myopathy other than PM or DM Any condition that precludes the ability to quantitate muscle strength Has severe interstitial lung disease or has a pulmonary damage VAS score ≥5 cm on the Myositis Damage Index (MDI) Presence of autoinflammatory disease Use of nonpermitted medications or treatments within the specified washout periods prior to screening Patient has had recent serious or ongoing infection, or risk for serious infection Any of the following laboratory values at Screening: Estimated glomerular filtration rate <45 mL/min Hemoglobin <10 g/dL White blood cell (WBC) count <3.0 × 109/L Absolute neutrophil count (ANC) <1.5 × 109/L (1500/mm3) Platelet count <100 × 109/L Serum AST or serum ALT >2.5 × ULN (unless considered consistent with muscle origin) Serum alkaline phosphatase >2.5 × ULN Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert's syndrome) Thyroid stimulating hormone outside of the central laboratory normal range Immunoglobulin G (IgG) <500 mg/dL. Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure, or prolonged QT interval Major surgery within 12 weeks before Screening or planned during the study period Clinical evidence of significant unstable or uncontrolled diseases Any active or suspected malignancy, including myeloproliferative or lymphoproliferative disorder, or history of documented malignancy within the last 5 years before Screening or within 3 years of diagnosis of myositis, except appropriately excised and cured cervical carcinoma in situ or basal or squamous cell carcinoma of the skin

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A<br>Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks Treatment Period 2: Placebo SC weekly for 16 weeks | Drug: KZR-616<br>* Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks<br>Drug: Placebo<br>* Subcutaneous injection for 16 weeks<br>|
| Other: Arm B<br>Treatment Period 1: Placebo SC weekly for 16 weeks Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks | Drug: KZR-616<br>* Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks<br>Drug: Placebo<br>* Subcutaneous injection for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure | Mean change from start to end of KZR-616 treatment in the Total Improvement Score (TIS), which ranges from 0 to 100. | From start to end of KZR-616 treatment for both sequence arms combined. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an increase ≥20 points on the TIS from start to end of KZR-616 treatment. |  | 16 weeks | 
| Proportion of patients from start to end of KZR-616 treatment meeting International Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement (DOI). |  | 16 weeks | 
| Absolute change from start to end of KZR-616 treatment in the IMACS individual core set activity measures (CSAMs) |  | 16 weeks | 
| Percent change from start to end of KZR-616 treatment in the IMACS individual CSAMs |  | 16 weeks | 
| For patients with DM, the mean change from start to end of KZR-616 treatment in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) |  | 16 weeks | 
| For patients with DM, the mean change from start to end of KZR-616 treatment in the Peak Pruritus Numeric Rating Scale. | The Peak Pruritus Numeric Rating Scale ranges from a score of 0 to 10, with 0 representing no itch and 10 representing the worst itch imaginable during the worst moment within a 24-hour recall period. | 16 weeks | 
| Safety and tolerability of KZR-616 in patients with PM or DM as assessed by monitoring incidence and severity of adverse events (AEs) |  | 40 weeks | 
| Peak plasma concentration (Cmax) following KZR-616 injection |  | Day 1 | 
| Time to peak plasma concentration (Tmax) following KZR-616 injection |  | Day 1 | 
| Area under the plasma concentration versus time curve (AUC) following KZR-616 injection |  | Day 1 | 
| Half life (T1/2) following KZR-616 injection |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myositis, Idiopathic inflammatory myopathies, Polymyositis, Dermatomyositis, Musculoskeletal Diseases, Muscular Diseases