A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP

A Phase 2 Randomized, Dose-blind, Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Autoimmune Hemolytic Anemia (AIHA) and Immune Thrombocytopenia (ITP)

This is a Phase 2 randomized, dose-blind, multicenter study designed to evaluate the safety, tolerability, efficacy, Pharmacokinetics (PK), and Pharmacodynamics (PD) of treatment with KZR-616 in patients with active Autoimmune Hemolytic Anemia or Immune Thrombocytopenia.

Inclusion Criteria:

1. Adult patients must be at least 18 years of age at the time of signing informed consent at Screening

2. Body Mass Index (BMI) equal to or greater than 18 kg/m2

3. Have a documented diagnosis of primary or secondary AIHA, ITP, or primary Evans syndrome

4. AIHA or ITP disease activity as follows::

   1. ITP: Per central or local laboratory assessments on 2 separate occasions ≥7 days apart during Screening, a mean Platelet (PLT) ≤30×109/L with no individual PLT >35×109/L; or for those patients receiving a constant dose of permitted treatments for ITP: a mean PLT <50×109/L, with no count >55×109/L
   2. AIHA: Hgb ≤10 g/dL and presence of any 2 of the following:

   i. Haptoglobin <lower limit of normal (LLN) ii. Corrected reticulocyte count >upper limit of normal (ULN) iii. LDH >ULN iv. Indirect bilirubin >ULN.

5. Documented inadequate response on intolerance to ≥1 standard treatment approach for AIHA or ≥2 standard treatment approaches for ITP

Exclusion Criteria:

1. Systemic Lupus Erythematosus (SLE) with confirmed anti-phospholipid antibody syndrome, the presence of positive lupus anti-coagulant test, moderate-high titer anti-cardiolipin IgG or IgM or moderate-high titer anti-beta2-globuilin IgG or IgM or severe central nervous system involvement

2. History of clinically significant coagulopathy, hereditary thrombocytopenia, anemia, or family history of thrombocytopenia

3. History of primary immunodeficiency

4. Use of nonpermitted medications within the specified washout periods prior to screening

5. Recent serious or ongoing infection, or risk for serious infection

6. Any of the following laboratory values at Screening:

   1. Estimated glomerular filtration rate (eGFR) <45 ml/min
   2. Absolute neutrophil count (ANC) <1.5×109/L (1500/mm3)
   3. Serum aspartate transaminase (AST), serum alanine transaminase (ALT) or serum alkaline phosphatase >2.5×ULN
   4. Thyroid stimulating hormone if outside of the central laboratory normal range and considered clinically significant
   5. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) >1.5×ULN
   6. Immunoglobulin G (IgG) <500 mg/dL
   7. For ITP patients only: total bilirubin >1.5×ULN (3×ULN for patients with documented Gilbert's syndrome).

7. Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure, or prolonged QT interval

8. Major surgery within 12 weeks before Screening or planned during the study period

9. History of any thrombotic or embolic event within 12 months prior to Screening

10. Clinical evidence of significant unstable or uncontrolled diseases

11. Any active or suspected malignancy or history of documented malignancy within the last 5 years before Screening, except appropriately excised and cured cervical carcinoma in situ or basal or squamous cell carcinoma of the skin, or non-muscle invasive bladder cancer