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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04039477




Registration number
NCT04039477
Ethics application status
Date submitted
26/07/2019
Date registered
31/07/2019
Date last updated
7/08/2020

Titles & IDs
Public title
A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP
Scientific 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)
Secondary ID [1] 0 0
KZR-616-005
Universal Trial Number (UTN)
Trial acronym
MARINA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autoimmune Hemolytic Anemia 0 0
Immune Thrombocytopenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Anaemia
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Blood 0 0 0 0
Anaemia
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KZR-616

Experimental: Arm A - KZR-616 30mg - KZR-616 30mg Subcutaneous (SC) injection weekly for 13 weeks

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


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean change from Baseline to Week 13 in hematologic parameters of interest in evaluable patients (Hgb for AIHA; Platelets [PLT] for ITP)
Timepoint [1] 0 0
13 weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
13 weeks
Secondary outcome [2] 0 0
Mean change from Baseline over time in hematologic parameters of interest (Hgb for AIHA; PLT for ITP)
Timepoint [2] 0 0
Through study completion, up to 25 weeks
Secondary outcome [3] 0 0
Proportion of patients with a response at Week 13
Timepoint [3] 0 0
13 weeks
Secondary outcome [4] 0 0
Proportion of patients over time with a response
Timepoint [4] 0 0
Through study completion, up to 25 weeks
Secondary outcome [5] 0 0
Time to response
Timepoint [5] 0 0
Through study completion, up to 25 weeks
Secondary outcome [6] 0 0
Proportion of patients over time with loss of response
Timepoint [6] 0 0
Through study completion, up to 25 weeks
Secondary outcome [7] 0 0
Proportion of patients over time with sustained response
Timepoint [7] 0 0
Through study completion, up to 25 weeks
Secondary outcome [8] 0 0
Mean change from Baseline over time in Hct
Timepoint [8] 0 0
Through study completion, up to 25 weeks
Secondary outcome [9] 0 0
Mean change from Baseline over time in Lactate Dehydrogenase (LDH)
Timepoint [9] 0 0
Through study completion, up to 25 weeks
Secondary outcome [10] 0 0
Change from Baseline over time in Patient Global Assessment scores
Timepoint [10] 0 0
Baseline and every 4 weeks for 25 weeks
Secondary outcome [11] 0 0
For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13
Timepoint [11] 0 0
13 weeks
Secondary outcome [12] 0 0
For AIHA: Number of blood transfusions and units of blood administered over time
Timepoint [12] 0 0
Through study completion, up to 25 weeks
Secondary outcome [13] 0 0
For ITP: Number of platelet transfusions and units of platelets administered over time
Timepoint [13] 0 0
Through study completion, up to 25 weeks
Secondary outcome [14] 0 0
Safety and tolerability of KZR-616 in patients with AIHA or ITP as assessed by monitoring incidence and severity of adverse events (AEs)
Timepoint [14] 0 0
Through study completion, up to 25 weeks
Secondary outcome [15] 0 0
Peak Plasma Concentration (Cmax) following KZR-616 injection
Timepoint [15] 0 0
Day 1
Secondary outcome [16] 0 0
Peak Plasma Concentration (Cmax) following KZR-616 injection
Timepoint [16] 0 0
Day 29
Secondary outcome [17] 0 0
Time to peak plasma concentration (Tmax) following KZR-616 injection
Timepoint [17] 0 0
Day 1
Secondary outcome [18] 0 0
Time to peak plasma concentration (Tmax) following KZR-616 injection
Timepoint [18] 0 0
Day 29
Secondary outcome [19] 0 0
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Timepoint [19] 0 0
Day 1
Secondary outcome [20] 0 0
Area under the plasma concentration versus time curve (AUC) following KZR-616 injection
Timepoint [20] 0 0
Day 29
Secondary outcome [21] 0 0
Half-life (T1/2) following KZR-616 injection
Timepoint [21] 0 0
Day 1
Secondary outcome [22] 0 0
Half-life (T1/2) following KZR-616 injection
Timepoint [22] 0 0
Day 29

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/07/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/08/2020
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
KZR Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Italy
State/province [11] 0 0
Bologna
Country [12] 0 0
Italy
State/province [12] 0 0
Genova
Country [13] 0 0
Poland
State/province [13] 0 0
Kraków
Country [14] 0 0
Poland
State/province [14] 0 0
Poznan
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Moscow
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Saint Petersburg

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kezar Life Sciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04039477
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kezar
Address 0 0
Kezar Life Sciences, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04039477