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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

Conditions
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Polycythemia Vera, Essential Thrombocythemia

Intervention / Treatment
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* Drug: Momelotinib


Participation Criteria
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Eligibility Criteria
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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 inducers within 1 week prior to the first dose of study drug QTc interval > 450 msec, unless attributed to bundle branch block

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Momelotinib 100 mg PV<br>Participants with polycythemia vera will receive 100 mg of momelotinib. | Drug: Momelotinib<br>* Momelotinib tablet administered orally once daily<br>* Other names: CYT387;|
| Experimental: Momelotinib 200 mg PV<br>Participants with polycythemia vera will receive 200 mg of momelotinib. | Drug: Momelotinib<br>* Momelotinib tablet administered orally once daily<br>* Other names: CYT387;|
| Experimental: Momelotinib 100 mg ET<br>Participants with essential thrombocythemia will receive 100 mg of momelotinib. | Drug: Momelotinib<br>* Momelotinib tablet administered orally once daily<br>* Other names: CYT387;|
| Experimental: Momelotinib 200 mg ET<br>Participants with essential thrombocythemia will receive 200 mg of momelotinib. | Drug: Momelotinib<br>* Momelotinib tablet administered orally once daily<br>* Other names: CYT387;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | 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 | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed overall response rate | 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. | Up to 24 weeks | 
| Proportion of participants with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks |  | Up to 24 weeks | 
| Proportion of participants with WBC < 10 x 10^9/L that lasts at least 4 weeks |  | Up to 24 weeks | 
| Proportion of participants with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks |  | Up to 24 weeks | 
| Proportion of participants with resolution of palpable splenomegaly that lasts at least 4 weeks |  | Up to 24 weeks | 
| 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 |  | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycythemia, Polycythemia Vera, Essential Thrombocythemia, Thrombocytosis, Myeloproliferative Disorders, Bone Marrow Diseases, Hematologic Diseases, Blood Coagulation Disorders, Blood Platelet Disorders, Hemorrhagic Disorders