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WithdrawnNCT04039477MARINAUpdated Aug 7, 2020

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

A Phase 2 interventional study of KZR-616 in Autoimmune Hemolytic Anemia and Immune Thrombocytopenia, sponsored by Kezar Life Sciences, Inc.. Withdrawn at 22 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-08-07.

Sponsored by Kezar Life Sciences, Inc. · Phase 2, Interventional, and Treatment

Why this study was withdrawn
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.
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Autoimmune Hemolytic Anemia
  • Immune Thrombocytopenia

Keywords

  • Autoimmune
  • Hemolytic
  • Anemia
  • Autoimmune Hemolytic Anemia
  • AIHA
  • Immune
  • Thrombocytopenia
  • Immune Thrombocytopenia
  • ITP
  • Blood disorders
  • Hematology
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    Arm A - KZR-616 30mg

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

    Drug: KZR-616

  • 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

Interventions

  • DrugKZR-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

05

What researchers measure

Primary outcomes

  1. 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 outcomes

  1. 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

  2. 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

  3. Proportion of patients with a response at Week 13

    Time frame: 13 weeks

  4. Proportion of patients over time with a response

    Time frame: Through study completion, up to 25 weeks

  5. Time to response

    Time frame: Through study completion, up to 25 weeks

  6. Proportion of patients over time with loss of response

    Time frame: Through study completion, up to 25 weeks

  7. Proportion of patients over time with sustained response

    Time frame: Through study completion, up to 25 weeks

  8. Mean change from Baseline over time in Hct

    Time frame: Through study completion, up to 25 weeks

  9. Mean change from Baseline over time in Lactate Dehydrogenase (LDH)

    Time frame: Through study completion, up to 25 weeks

  10. 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."

    Time frame: Baseline and every 4 weeks for 25 weeks

  11. For AIHA: Proportion of patients with an Hgb >12 g/dL or 2 g/dL higher than Baseline at W13

    Time frame: 13 weeks

  12. For AIHA: Number of blood transfusions and units of blood administered over time

    Time frame: Through study completion, up to 25 weeks

  13. For ITP: Number of platelet transfusions and units of platelets administered over time

    Time frame: Through study completion, up to 25 weeks

  14. 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

  15. Peak Plasma Concentration (Cmax) following KZR-616 injection

    Time frame: Day 1

  16. Peak Plasma Concentration (Cmax) following KZR-616 injection

    Time frame: Day 29

  17. Time to peak plasma concentration (Tmax) following KZR-616 injection

    Time frame: Day 1

  18. Time to peak plasma concentration (Tmax) following KZR-616 injection

    Time frame: Day 29

  19. Area under the plasma concentration versus time curve (AUC) following KZR-616 injection

    Time frame: Day 1

  20. Area under the plasma concentration versus time curve (AUC) following KZR-616 injection

    Time frame: Day 29

  21. Half-life (T1/2) following KZR-616 injection

    Time frame: Day 1

  22. Half-life (T1/2) following KZR-616 injection

    Time frame: Day 29

06

Study locations

22 sites
  • KZR Research Site
    Los Angeles, California 90007, United States
  • KZR Research Site
    San Francisco, California 94143, United States
  • KZR Research Site
    Jacksonville, Florida 32224, United States
  • KZR Research Site
    Miami Lakes, Florida 33014, United States
  • KZR Research Site
    Tampa, Florida 33612, United States
  • KZR Research Site
    Peoria, Illinois 61615, United States
  • KZR Research Site
    Boston, Massachusetts 02114, United States
  • KZR Research Site
    Minneapolis, Minnesota 55454, United States
  • KZR-616 Research Site
    Rochester, Minnesota 55455, United States
  • KZR Research Site
    Morristown, New Jersey 07960, United States
  • KZR Research Site
    Bronx, New York 10467, United States
  • KZR Research Site
    Greenville, North Carolina 27834, United States
  • KZR Research Site
    Cleveland, Ohio 44195, United States
  • KZR Research Site
    Columbus, Ohio 43210, United States
  • KZR Research Site
    Webster, Texas 77598, United States
  • KZR Research Site
    Woolloongabba, Australia
  • KZR Research Site
    Bologna, Italy
  • KZR Research Site
    Genova, Italy
  • KZR Research Site
    Kraków, Poland
  • KZR Research Site
    Poznań, Poland
  • KZR Research Site
    Moscow, Russian Federation
  • KZR Research Site
    Saint Petersburg, Russian Federation
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT04039477
Lead sponsor
Kezar Life Sciences, Inc.
Responsible party
Sponsor
First posted
Jul 31, 2019
Start date
Jul 2020 (estimated)
Primary completion
Aug 5, 2020
Completion
Aug 5, 2020
Last update
Aug 7, 2020

Study contacts

Kezar
study director · Kezar Life Sciences, Inc.

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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