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

Inclusion Criteria

• Adult patients at least 18 years of age
• Body Mass Index (BMI) of 18 to 40 kg/m^2
• Diagnosis of probable or definite DM or PM by the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria
• Must have their data reviewed by an adjudication committee to 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 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