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

Sponsor

Sierra Oncology, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT01998828

Collaborator

(none)

Enrollment

Locations

Arms

14.5

Actual Duration (Months)

2.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera Essential Thrombocythemia	Drug: Momelotinib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Start Date :

Feb 19, 2014

Actual Primary Completion Date :

Mar 17, 2015

Actual Study Completion Date :

May 7, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

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

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 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country
1	Scottsdale	Arizona	United States
2	Whittier	California	United States
3	Tupelo	Mississippi	United States
4	Saint Louis	Missouri	United States
5	Houston	Texas	United States
6	Frankston	Victoria	Australia
7	Parkville	Victoria	Australia
8	Vancouver	British Columbia	Canada
9	Toronto	Ontario	Canada
10	Montreal	Quebec	Canada
11	La Tronche		France
12	Nantes Cedex 1		France
13	Paris		France
14	Dresden		Germany
15	Minden		Germany