Clinical trial NCT04039477: A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Autoimmune Hemolytic Anemia
Immune Thrombocytopenia
Keywords: Autoimmune
Hemolytic
Anemia
Autoimmune Hemolytic Anemia
AIHA
Immune
Thrombocytopenia
Immune Thrombocytopenia
ITP
Blood disorders
Hematology
Lead sponsor: Kezar Life Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean change from Baseline to Week 13 in hematologic parameters of interest in evaluable patients (Hgb for AIHA; Platelets [PLT] for ITP)
timeFrame: 13 weeks
Secondary outcomes:
measure: Mean change from Baseline to Week 13 in hematologic parameters of interest (Hgb for AIHA; PLT for ITP) in the intent to treat (ITT) population
timeFrame: 13 weeks
measure: Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP)
timeFrame: Through study completion, up to 25 weeks
measure: Proportion of patients with a response at Week 13
timeFrame: 13 weeks
measure: Proportion of patients over time with a response
timeFrame: Through study completion, up to 25 weeks
measure: Time to response
timeFrame: Through study completion, up to 25 weeks
measure: Proportion of patients over time with loss of response
timeFrame: Through study completion, up to 25 weeks
measure: Proportion of patients over time with sustained response
timeFrame: Through study completion, up to 25 weeks
measure: Mean change from Baseline over time in Hct
timeFrame: Through study completion, up to 25 weeks
measure: Mean change from Baseline over time in Lactate Dehydrogenase (LDH)
timeFrame: Through study completion, up to 25 weeks
measure: Change from Baseline over time in Patient Global Assessment scores
timeFrame: Baseline and every 4 weeks for 25 weeks
measure: For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13
timeFrame: 13 weeks
measure: For AIHA: Number of blood transfusions and units of blood administered over time
timeFrame: Through study completion, up to 25 weeks
measure: For ITP: Number of platelet transfusions and units of platelets administered over time
timeFrame: Through study completion, up to 25 weeks
measure: Safety and tolerability of KZR-616 in patients with AIHA or ITP as assessed by monitoring incidence and severity of adverse events (AEs)
timeFrame: Through study completion, up to 25 weeks
measure: Peak Plasma Concentration (Cmax) following KZR-616 injection
timeFrame: Day 1
measure: Peak Plasma Concentration (Cmax) following KZR-616 injection
timeFrame: Day 29
measure: Time to peak plasma concentration (Tmax) following KZR-616 injection
timeFrame: Day 1
measure: Time to peak plasma concentration (Tmax) following KZR-616 injection
timeFrame: Day 29
measure: Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
timeFrame: Day 1
measure: Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
timeFrame: Day 29
measure: Half-life (T1/2) following KZR-616 injection
timeFrame: Day 1
measure: Half-life (T1/2) following KZR-616 injection
timeFrame: Day 29
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: KZR Research Site
state: California
city: San Francisco
country: United States
facility: KZR Research Site
state: California
city: Jacksonville
country: United States
facility: KZR Research Site
state: Florida
city: Miami Lakes
country: United States
facility: KZR Research Site
state: Florida
city: Tampa
country: United States
facility: KZR Research Site
state: Florida
city: Peoria
country: United States
facility: KZR Research Site
state: Illinois
city: Boston
country: United States
facility: KZR Research Site
state: Massachusetts
city: Minneapolis
country: United States
facility: KZR Research Site
state: Minnesota
city: Rochester
country: United States
facility: KZR-616 Research Site
state: Minnesota
city: Morristown
country: United States
facility: KZR Research Site
state: New Jersey
city: Bronx
country: United States
facility: KZR Research Site
state: New York
city: Greenville
country: United States
facility: KZR Research Site
state: North Carolina
city: Cleveland
country: United States
facility: KZR Research Site
state: Ohio
city: Columbus
country: United States
facility: KZR Research Site
state: Ohio
city: Webster
country: United States
facility: KZR Research Site
state: Texas
city: Woolloongabba
country: Australia
facility: KZR Research Site
city: Bologna
country: Italy
facility: KZR Research Site
city: Genova
country: Italy
facility: KZR Research Site
city: Kraków
country: Poland
facility: KZR Research Site
city: Poznań
country: Poland
facility: KZR Research Site
city: Moscow
country: Russian Federation
facility: KZR Research Site
city: Saint Petersburg
country: Russian Federation
facility: KZR Research Site
Study officials:
affiliation: Kezar Life Sciences, Inc.
name: Kezar
role: STUDY_DIRECTOR
References: