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

Immune Thrombocytopenia Clinical Trial

— MARINA  

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04039477
• Other study ID #: KZR-616-005
• Status: Withdrawn
• Phase: Phase 2
• Start date: July 2020
• Est. completion date: August 5, 2020

Study information

• Verified date: August 2020
• Source: Kezar Life Sciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 5, 2020
• Est. primary completion date: August 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Anemia
• Hemolysis
• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• KZR-616
Patients will receive KZR-616 SC once weekly. Patients assigned to Arm A will receive 30 mg for 13 weeks and patients assigned to Arm B will receive 30 mg for 1 week then 45 mg for 12 weeks

Locations

Country	Name	City	State
Australia	KZR Research Site	Woolloongabba
Italy	KZR Research Site	Bologna
Italy	KZR Research Site	Genova
Poland	KZR Research Site	Kraków
Poland	KZR Research Site	Poznan
Russian Federation	KZR Research Site	Moscow
Russian Federation	KZR Research Site	Saint Petersburg
United States	KZR Research Site	Boston	Massachusetts
United States	KZR Research Site	Bronx	New York
United States	KZR Research Site	Cleveland	Ohio
United States	KZR Research Site	Columbus	Ohio
United States	KZR Research Site	Greenville	North Carolina
United States	KZR Research Site	Jacksonville	Florida
United States	KZR Research Site	Los Angeles	California
United States	KZR Research Site	Miami Lakes	Florida
United States	KZR Research Site	Minneapolis	Minnesota
United States	KZR Research Site	Morristown	New Jersey
United States	KZR Research Site	Peoria	Illinois
United States	KZR-616 Research Site	Rochester	Minnesota
United States	KZR Research Site	San Francisco	California
United States	KZR Research Site	Tampa	Florida
United States	KZR Research Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Kezar Life Sciences, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change from Baseline to Week 13 in hematologic parameters of interest in evaluable patients (Hgb for AIHA; Platelets [PLT] for ITP)		13 weeks
Secondary	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		13 weeks
Secondary	Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP)		Through study completion, up to 25 weeks
Secondary	Proportion of patients with a response at Week 13		13 weeks
Secondary	Proportion of patients over time with a response		Through study completion, up to 25 weeks
Secondary	Time to response		Through study completion, up to 25 weeks
Secondary	Proportion of patients over time with loss of response		Through study completion, up to 25 weeks
Secondary	Proportion of patients over time with sustained response		Through study completion, up to 25 weeks
Secondary	Mean change from Baseline over time in Hct		Through study completion, up to 25 weeks
Secondary	Mean change from Baseline over time in Lactate Dehydrogenase (LDH)		Through study completion, up to 25 weeks
Secondary	Change from Baseline over time in Patient Global Assessment scores	The PtGA is a visual analog scale (VAS) ranging from 0 to 100. Patients will provide a global rating of their disease, for the day of the visit, in response to the statement "Considering all the ways that your disease affects you, please rate how you are feeling today by clicking or tapping on the line:" using a 100-point VAS where 0 is "very good, no symptoms" and 100 is "very poor, very severe symptoms."	Baseline and every 4 weeks for 25 weeks
Secondary	For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13		13 weeks
Secondary	For AIHA: Number of blood transfusions and units of blood administered over time		Through study completion, up to 25 weeks
Secondary	For ITP: Number of platelet transfusions and units of platelets administered over time		Through study completion, up to 25 weeks
Secondary	Safety and tolerability of KZR-616 in patients with AIHA or ITP as assessed by monitoring incidence and severity of adverse events (AEs)		Through study completion, up to 25 weeks
Secondary	Peak Plasma Concentration (Cmax) following KZR-616 injection		Day 1
Secondary	Peak Plasma Concentration (Cmax) following KZR-616 injection		Day 29
Secondary	Time to peak plasma concentration (Tmax) following KZR-616 injection		Day 1
Secondary	Time to peak plasma concentration (Tmax) following KZR-616 injection		Day 29
Secondary	Area under the plasma concentration versus time curve (AUC) following KZR-616 injection		Day 1
Secondary	Area under the plasma concentration versus time curve (AUC) following KZR-616 injection		Day 29
Secondary	Half-life (T1/2) following KZR-616 injection		Day 1
Secondary	Half-life (T1/2) following KZR-616 injection		Day 29