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

Sponsor

Kezar Life Sciences, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04039477

Collaborator

(none)

Enrollment

Locations

Arms

1.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Hemolytic Anemia Immune Thrombocytopenia	Drug: KZR-616	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Jul 1, 2020

Actual Primary Completion Date :

Aug 5, 2020

Actual Study Completion Date :

Aug 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A - KZR-616 30mg KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks	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
Experimental: Arm B - KZR-616 45mg KZR-616 30 mg SC injection weekly for 1 dose then 45mg weekly for 12 weeks.	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

Arm

Intervention/Treatment

Experimental: Arm A - KZR-616 30mg

KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks

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

Experimental: Arm B - KZR-616 45mg

KZR-616 30 mg SC injection weekly for 1 dose then 45mg weekly for 12 weeks.

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP) [Through study completion, up to 25 weeks]
Proportion of patients with a response at Week 13 [13 weeks]
Proportion of patients over time with a response [Through study completion, up to 25 weeks]
Time to response [Through study completion, up to 25 weeks]
Proportion of patients over time with loss of response [Through study completion, up to 25 weeks]
Proportion of patients over time with sustained response [Through study completion, up to 25 weeks]
Mean change from Baseline over time in Hct [Through study completion, up to 25 weeks]
Mean change from Baseline over time in Lactate Dehydrogenase (LDH) [Through study completion, up to 25 weeks]
Change from Baseline over time in Patient Global Assessment scores [Baseline and every 4 weeks for 25 weeks]
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."
For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13 [13 weeks]
For AIHA: Number of blood transfusions and units of blood administered over time [Through study completion, up to 25 weeks]
For ITP: Number of platelet transfusions and units of platelets administered over time [Through study completion, up to 25 weeks]
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]
Peak Plasma Concentration (Cmax) following KZR-616 injection [Day 1]
Peak Plasma Concentration (Cmax) following KZR-616 injection [Day 29]
Time to peak plasma concentration (Tmax) following KZR-616 injection [Day 1]
Time to peak plasma concentration (Tmax) following KZR-616 injection [Day 29]
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection [Day 1]
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection [Day 29]
Half-life (T1/2) following KZR-616 injection [Day 1]
Half-life (T1/2) following KZR-616 injection [Day 29]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients must be at least 18 years of age at the time of signing informed consent at Screening
Body Mass Index (BMI) equal to or greater than 18 kg/m2
Have a documented diagnosis of primary or secondary AIHA, ITP, or primary Evans syndrome
AIHA or ITP disease activity as follows::
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

AIHA: Hgb ≤10 g/dL and presence of any 2 of the following:

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

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

Exclusion Criteria:

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
History of clinically significant coagulopathy, hereditary thrombocytopenia, anemia, or family history of thrombocytopenia
History of primary immunodeficiency
Use of nonpermitted medications within the specified washout periods prior to screening
Recent serious or ongoing infection, or risk for serious infection
Any of the following laboratory values at Screening:
Estimated glomerular filtration rate (eGFR) <45 ml/min
Absolute neutrophil count (ANC) <1.5×109/L (1500/mm3)
Serum aspartate transaminase (AST), serum alanine transaminase (ALT) or serum alkaline phosphatase >2.5×ULN
Thyroid stimulating hormone if outside of the central laboratory normal range and considered clinically significant
International normalized ratio (INR) or activated partial thromboplastin time (aPTT) >1.5×ULN
Immunoglobulin G (IgG) <500 mg/dL
For ITP patients only: total bilirubin >1.5×ULN (3×ULN for patients with documented Gilbert's syndrome).
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
History of any thrombotic or embolic event within 12 months prior to Screening
Clinical evidence of significant unstable or uncontrolled diseases
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	KZR Research Site	Los Angeles	California	United States	90007
2	KZR Research Site	San Francisco	California	United States	94143
3	KZR Research Site	Jacksonville	Florida	United States	32224
4	KZR Research Site	Miami Lakes	Florida	United States	33014
5	KZR Research Site	Tampa	Florida	United States	33612
6	KZR Research Site	Peoria	Illinois	United States	61615
7	KZR Research Site	Boston	Massachusetts	United States	02114
8	KZR Research Site	Minneapolis	Minnesota	United States	55454
9	KZR-616 Research Site	Rochester	Minnesota	United States	55455
10	KZR Research Site	Morristown	New Jersey	United States	07960
11	KZR Research Site	Bronx	New York	United States	10467
12	KZR Research Site	Greenville	North Carolina	United States	27834
13	KZR Research Site	Cleveland	Ohio	United States	44195
14	KZR Research Site	Columbus	Ohio	United States	43210
15	KZR Research Site	Webster	Texas	United States	77598
16	KZR Research Site	Woolloongabba		Australia
17	KZR Research Site	Bologna		Italy
18	KZR Research Site	Genova		Italy
19	KZR Research Site	Kraków		Poland
20	KZR Research Site	Poznań		Poland
21	KZR Research Site	Moscow		Russian Federation
22	KZR Research Site	Saint Petersburg		Russian Federation