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

Phase 2

Terminated

• Conditions: Polycythemia Vera; Essential Thrombocythemia
• Interventions: Drug: Momelotinib

• Registration Number: NCT01998828
• Lead Sponsor: Sierra Oncology LLC - a GSK company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-25
• Study First Submitted QC: 2013-11-25
• Study First Posted: 2013-12-02
• Study Start: 2014-02-19
• Primary Completion: 2015-03-17
• Study Completion: 2015-05-07
• Disposition First Submitted: 2016-04-26
• Disposition First Submitted QC: 2016-04-26
• Disposition First Posted: 2016-05-25
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-14
• Last Update Posted: 2020-04-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Momelotinib 200 mg ET	Momelotinib	Participants with essential thrombocythemia will receive 200 mg of momelotinib.
Momelotinib 100 mg PV	Momelotinib	Participants with polycythemia vera will receive 100 mg of momelotinib.
Momelotinib 200 mg PV	Momelotinib	Participants with polycythemia vera will receive 200 mg of momelotinib.
Momelotinib 100 mg ET	Momelotinib	Participants with essential thrombocythemia will receive 100 mg of momelotinib.

Primary Outcome Measures

Name	Time	Method
Overall response rate	Up to 24 weeks	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

Name	Time	Method
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
Confirmed overall response rate	Up to 24 weeks	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 WBC < 10 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 hematocrit < 45% in the absence of phlebotomy 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