- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04039477
A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP (MARINA)
August 5, 2020 updated by: Kezar Life Sciences, Inc.
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.
Study Overview
Status
Withdrawn
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Woolloongabba, Australia
- KZR Research Site
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Bologna, Italy
- KZR Research Site
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Genova, Italy
- KZR Research Site
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Kraków, Poland
- KZR Research Site
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Poznań, Poland
- KZR Research Site
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Moscow, Russian Federation
- KZR Research Site
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Saint Petersburg, Russian Federation
- KZR Research Site
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California
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Los Angeles, California, United States, 90007
- KZR Research Site
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San Francisco, California, United States, 94143
- KZR Research Site
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Florida
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Jacksonville, Florida, United States, 32224
- KZR Research Site
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Miami Lakes, Florida, United States, 33014
- KZR Research Site
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Tampa, Florida, United States, 33612
- KZR Research Site
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Illinois
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Peoria, Illinois, United States, 61615
- KZR Research Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- KZR Research Site
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Minnesota
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Minneapolis, Minnesota, United States, 55454
- KZR Research Site
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Rochester, Minnesota, United States, 55455
- KZR-616 Research Site
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New Jersey
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Morristown, New Jersey, United States, 07960
- KZR Research Site
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New York
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Bronx, New York, United States, 10467
- KZR Research Site
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North Carolina
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Greenville, North Carolina, United States, 27834
- KZR Research Site
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Ohio
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Cleveland, Ohio, United States, 44195
- KZR Research Site
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Columbus, Ohio, United States, 43210
- KZR Research Site
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Texas
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Webster, Texas, United States, 77598
- KZR Research Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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:
i. 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Arm A - KZR-616 30mg
KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks
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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
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EXPERIMENTAL: Arm B - KZR-616 45mg
KZR-616 30 mg SC injection weekly for 1 dose then 45mg weekly for 12 weeks.
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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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Mean change from Baseline to Week 13 in hematologic parameters of interest in evaluable patients (Hgb for AIHA; Platelets [PLT] for ITP)
Time Frame: 13 weeks
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13 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to peak plasma concentration (Tmax) following KZR-616 injection
Time Frame: Day 1
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Day 1
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Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Time Frame: Day 1
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Day 1
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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
Time Frame: 13 weeks
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13 weeks
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Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP)
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Proportion of patients with a response at Week 13
Time Frame: 13 weeks
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13 weeks
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Proportion of patients over time with a response
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Time to response
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Proportion of patients over time with loss of response
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Proportion of patients over time with sustained response
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Mean change from Baseline over time in Hct
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Mean change from Baseline over time in Lactate Dehydrogenase (LDH)
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Change from Baseline over time in Patient Global Assessment scores
Time Frame: Baseline and every 4 weeks for 25 weeks
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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."
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Baseline and every 4 weeks for 25 weeks
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For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13
Time Frame: 13 weeks
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13 weeks
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For AIHA: Number of blood transfusions and units of blood administered over time
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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For ITP: Number of platelet transfusions and units of platelets administered over time
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Safety and tolerability of KZR-616 in patients with AIHA or ITP as assessed by monitoring incidence and severity of adverse events (AEs)
Time Frame: Through study completion, up to 25 weeks
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Through study completion, up to 25 weeks
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Peak Plasma Concentration (Cmax) following KZR-616 injection
Time Frame: Day 1
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Day 1
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Peak Plasma Concentration (Cmax) following KZR-616 injection
Time Frame: Day 29
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Day 29
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Time to peak plasma concentration (Tmax) following KZR-616 injection
Time Frame: Day 29
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Day 29
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Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Time Frame: Day 29
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Day 29
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Half-life (T1/2) following KZR-616 injection
Time Frame: Day 1
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Day 1
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Half-life (T1/2) following KZR-616 injection
Time Frame: Day 29
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Day 29
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
July 1, 2020
Primary Completion (ACTUAL)
August 5, 2020
Study Completion (ACTUAL)
August 5, 2020
Study Registration Dates
First Submitted
July 26, 2019
First Submitted That Met QC Criteria
July 29, 2019
First Posted (ACTUAL)
July 31, 2019
Study Record Updates
Last Update Posted (ACTUAL)
August 7, 2020
Last Update Submitted That Met QC Criteria
August 5, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura, Thrombocytopenic
- Purpura
- Anemia
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
- Hemolysis
- Anemia, Hemolytic
- Anemia, Hemolytic, Autoimmune
Other Study ID Numbers
- KZR-616-005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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