Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

This study is currently recruiting participants.
Verified March 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01998828
First received: November 25, 2013
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.


Condition Intervention Phase
Polycythemia Vera
Essential Thrombocythemia
Drug: Momelotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    For the PV Cohort, overall response rate (ORR) is defined as the proportion of participants with all of the following at some point during the treatment period:

    • Hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks
    • White blood cell (WBC) count < 10 x 10^9/L that lasts at least 4 weeks
    • Platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks
    • Resolution of palpable splenomegaly that lasts at least 4 weeks

    For the ET Cohort, overall response rate is defined as the proportion of participants with all of the following at some point during the treatment period:

    • WBC count < 10 x 10^9/L that lasts at least 4 weeks
    • Platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks
    • Resolution of palpable splenomegaly that lasts at least 4 weeks


Secondary Outcome Measures:
  • Confirmed overall response rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Confirmed overall response rate is defined as the proportion of participants who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks.

  • Proportion of participants with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with WBC < 10 x 10^9/L that lasts at least 4 weeks [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with resolution of palpable splenomegaly that lasts at least 4 weeks [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with ≥ 10 point decrease in modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) compared to baseline that lasts at least 12 weeks [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: February 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Momelotinib 100 mg PV
Participants with polycythemia vera will receive 100 mg of momelotinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Experimental: Momelotinib 200 mg PV
Participants with polycythemia vera will receive 200 mg of momelotinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Experimental: Momelotinib 100 mg ET
Participants with essential thrombocythemia will receive 100 mg of momelotinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Experimental: Momelotinib 200 mg ET
Participants with essential thrombocythemia will receive 200 mg of momelotinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of either PV or ET as defined by the 2008 World Health Organization (WHO) Diagnostic Criteria
  • Requires treatment for PV or ET, in the opinion of the study investigator
  • Intolerant of, resistant to, or refuses current or available treatment for PV or ET
  • Direct bilirubin ≤ 2.0 x upper limit of the normal range (ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
  • Calculated creatinine clearance (CrCl) of ≥ 45 mL/min
  • Life expectancy > 24 weeks
  • Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
  • Females who are nursing must agree to discontinue nursing before the first dose of study drug
  • Able to comprehend and willing to sign informed consent form

Exclusion Criteria:

  • Prior splenectomy
  • Uncontrolled intercurrent illness, per protocol
  • Known positive status for human immunodeficiency virus (HIV)
  • Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
  • Myeloproliferative neoplasm-directed therapy, other than aspirin, hydroxyurea, anagrelide, and/or phlebotomy, within 21 days prior to the first dose of study drug
  • Anagrelide within 7 days prior to the first dose of study drug
  • Presence of peripheral neuropathy ≥ Grade 2
  • Unwilling or unable to take oral medication
  • Prior use of a JAK1 or JAK2 inhibitor
  • Use of strong CYP3A4 inhibitors or strong inducers CYP3A4 within 1 week prior to the first dose of study drug
  • QTc interval > 450 msec, unless attributed to bundle branch block
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01998828

Locations
United States, California
Innovative Clinical Research Institute Recruiting
Whittier, California, United States, 90603
Contact: Kristen Bettino, CCRP    562-693-4477    kbettino@AIResearch.us   
Principal Investigator: Daniel Huang, MD         
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Peter Lee, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01998828     History of Changes
Other Study ID Numbers: GS-US-354-0101, 2013-004105-11
Study First Received: November 25, 2013
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada

Keywords provided by Gilead Sciences:
Polycythemia
Polycythemia Vera
Essential Thrombocythemia
Thrombocytosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on April 17, 2014