A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP (MARINA)
Primary Purpose
Autoimmune Hemolytic Anemia, Immune Thrombocytopenia
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KZR-616
Sponsored by
About this trial
This is an interventional treatment trial for Autoimmune Hemolytic Anemia focused on measuring Autoimmune, Hemolytic, Anemia, Autoimmune Hemolytic Anemia, AIHA, Immune, Thrombocytopenia, Immune Thrombocytopenia, ITP, Blood disorders, Hematology
Eligibility Criteria
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
Sites / Locations
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR-616 Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
- KZR Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A - KZR-616 30mg
Arm B - KZR-616 45mg
Arm Description
KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks
KZR-616 30 mg SC injection weekly for 1 dose then 45mg weekly for 12 weeks.
Outcomes
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)
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
Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP)
Proportion of patients with a response at Week 13
Proportion of patients over time with a response
Time to response
Proportion of patients over time with loss of response
Proportion of patients over time with sustained response
Mean change from Baseline over time in Hct
Mean change from Baseline over time in Lactate Dehydrogenase (LDH)
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."
For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13
For AIHA: Number of blood transfusions and units of blood administered over time
For ITP: Number of platelet transfusions and units of platelets administered over time
Safety and tolerability of KZR-616 in patients with AIHA or ITP as assessed by monitoring incidence and severity of adverse events (AEs)
Peak Plasma Concentration (Cmax) following KZR-616 injection
Peak Plasma Concentration (Cmax) following KZR-616 injection
Time to peak plasma concentration (Tmax) following KZR-616 injection
Time to peak plasma concentration (Tmax) following KZR-616 injection
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Half-life (T1/2) following KZR-616 injection
Half-life (T1/2) following KZR-616 injection
Full Information
NCT ID
NCT04039477
First Posted
July 26, 2019
Last Updated
August 5, 2020
Sponsor
Kezar Life Sciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04039477
Brief Title
A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Clinical trial activity slowdown due to COVID-19 pandemic, high screen fail rate, and lack of enrollment led to the decision to withdraw the MARINA study.
Study Start Date
July 2020 (Anticipated)
Primary Completion Date
August 5, 2020 (Actual)
Study Completion Date
August 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kezar Life Sciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Hemolytic Anemia, Immune Thrombocytopenia
Keywords
Autoimmune, Hemolytic, Anemia, Autoimmune Hemolytic Anemia, AIHA, Immune, Thrombocytopenia, Immune Thrombocytopenia, ITP, Blood disorders, Hematology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A - KZR-616 30mg
Arm Type
Experimental
Arm Description
KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks
Arm Title
Arm B - KZR-616 45mg
Arm Type
Experimental
Arm Description
KZR-616 30 mg SC injection weekly for 1 dose then 45mg weekly for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
KZR-616
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Proportion of patients with a response at Week 13
Time Frame
13 weeks
Title
Proportion of patients over time with a response
Time Frame
Through study completion, up to 25 weeks
Title
Time to response
Time Frame
Through study completion, up to 25 weeks
Title
Proportion of patients over time with loss of response
Time Frame
Through study completion, up to 25 weeks
Title
Proportion of patients over time with sustained response
Time Frame
Through study completion, up to 25 weeks
Title
Mean change from Baseline over time in Hct
Time Frame
Through study completion, up to 25 weeks
Title
Mean change from Baseline over time in Lactate Dehydrogenase (LDH)
Time Frame
Through study completion, up to 25 weeks
Title
Change from Baseline over time in Patient Global Assessment scores
Description
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."
Time Frame
Baseline and every 4 weeks for 25 weeks
Title
For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13
Time Frame
13 weeks
Title
For AIHA: Number of blood transfusions and units of blood administered over time
Time Frame
Through study completion, up to 25 weeks
Title
For ITP: Number of platelet transfusions and units of platelets administered over time
Time Frame
Through study completion, up to 25 weeks
Title
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
Title
Peak Plasma Concentration (Cmax) following KZR-616 injection
Time Frame
Day 1
Title
Peak Plasma Concentration (Cmax) following KZR-616 injection
Time Frame
Day 29
Title
Time to peak plasma concentration (Tmax) following KZR-616 injection
Time Frame
Day 1
Title
Time to peak plasma concentration (Tmax) following KZR-616 injection
Time Frame
Day 29
Title
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Time Frame
Day 1
Title
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Time Frame
Day 29
Title
Half-life (T1/2) following KZR-616 injection
Time Frame
Day 1
Title
Half-life (T1/2) following KZR-616 injection
Time Frame
Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kezar
Organizational Affiliation
Kezar Life Sciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
KZR Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
KZR Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
KZR Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
KZR Research Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
KZR Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
KZR Research Site
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
KZR Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
KZR Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
KZR-616 Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
KZR Research Site
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
KZR Research Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
KZR Research Site
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
KZR Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
KZR Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
KZR Research Site
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
KZR Research Site
City
Woolloongabba
Country
Australia
Facility Name
KZR Research Site
City
Bologna
Country
Italy
Facility Name
KZR Research Site
City
Genova
Country
Italy
Facility Name
KZR Research Site
City
Kraków
Country
Poland
Facility Name
KZR Research Site
City
Poznań
Country
Poland
Facility Name
KZR Research Site
City
Moscow
Country
Russian Federation
Facility Name
KZR Research Site
City
Saint Petersburg
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP
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