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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01969838




Registration number
NCT01969838
Ethics application status
Date submitted
22/10/2013
Date registered
25/10/2013
Date last updated
15/04/2020

Titles & IDs
Public title
Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
Scientific title
A Phase 3, Randomized, Double-blind Active-controlled Study Evaluating Momelotinib vs. Ruxolitinib in Subjects With Primary Myelofibrosis (PMF) or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Secondary ID [1] 0 0
2013-002707-33
Secondary ID [2] 0 0
GS-US-352-0101
Universal Trial Number (UTN)
Trial acronym
Simplify 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
Post-Polycythemia Vera Myelofibrosis 0 0
Post-Essential Thrombocythemia Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Momelotinib
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Placebo to match momelotinib
Treatment: Drugs - Placebo to match ruxolitinib

Experimental: Momelotinib - Participants will receive momelotinib plus placebo to match ruxolitinib.

Active Comparator: Ruxolitinib - Participants will receive ruxolitinib plus placebo to match momelotinib.


Treatment: Drugs: Momelotinib
Momelotinib tablet administered orally once daily

Treatment: Drugs: Ruxolitinib
Ruxolitinib tablets administered orally twice daily

Treatment: Drugs: Placebo to match momelotinib
Placebo to match momelotinib tablets administered orally once daily

Treatment: Drugs: Placebo to match ruxolitinib
Placebo to match ruxolitinib tablets administered orally twice daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Splenic response rate at Week 24 - Splenic response rate at Week 24 is defined as the proportion of participants achieving a = 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT.
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Response rate in total symptom score at Week 24 - Total symptom score (TSS) is defined as the proportion of participants who achieve a = 50% reduction in TSS from baseline to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) v2.0 diary.
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Rate of red blood cell (RBC) transfusion through Week 24 - Rate of RBC transfusion is defined as the average number of RBC units per participant per month.
Timepoint [2] 0 0
Baseline to Week 24
Secondary outcome [3] 0 0
RBC transfusion independence rate at Week 24 - RBC transfusion independence is the proportion of participants who are transfusion independent at Week 24, defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the prior 12 weeks.
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
RBC transfusion dependence rate at Week 24 - RBC transfusion dependence is the proportion of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the prior 8 weeks.
Timepoint [4] 0 0
Week 24

Eligibility
Key inclusion criteria
Key

- Palpable splenomegaly at least 5 cm below the left costal margin

- Confirmed diagnosis of PMF or post-PV/ET MF

- Requires myelofibrosis therapy, in the opinion of the investigator

- Classified as high risk OR intermediate-2 risk as defined by the International
Prognostic Scoring System (IPSS) for PMF, or intermediate-1 risk (IPSS) associated
with symptomatic splenomegaly, hepatomegaly, anemia (hemoglobin < 10.0 g/dL), and/or
unresponsive to available therapy

- Acceptable laboratory assessment obtained within 14 days prior to the first dose of
study drug:

- Absolute neutrophil count (ANC) = 0.75 x 10^9/L in the absence of growth factor
in the prior 7 days

- Platelet Count = 50 x 10^9/L (= 100 x 10^9/L if aspartate aminotransferase [AST]
or alanine aminotransferase [ALT] is = 2 x the upper limit of the normal range
[ULN]) in the absence of platelet transfusion(s) or thrombopoietin mimetics in
the prior 7 days

- Peripheral blood blast count < 10%

- AST and ALT = 3 x ULN (= 5 x ULN if liver is involved by extramedullary
hematopoiesis as judged by the investigator or if related to iron chelator
therapy that was started within the prior 60 days)

- Calculated creatinine clearance (CrCL) of = 45 mL/min

- Direct bilirubin = 2.0 x ULN

- Life expectancy of > 24 weeks

- Males and females of childbearing potential 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 understand and willing to sign the informed consent form

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior splenectomy

- Splenic irradiation within 3 months prior to the first dose of study drug

- Eligible for allogeneic bone marrow or stem cell transplantation

- Uncontrolled inter-current illness, per protocol.

- Known positive status for human immunodeficiency virus (HIV)

- Chronic active or acute viral hepatitis A, B, or C infection, or a hepatitis B or C
carrier

- Prior use of a JAK1 or JAK2 inhibitor

- Use of chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or
investigational therapy within 4 weeks of the first dose of study drug

- Presence of peripheral neuropathy = Common Terminology Criteria for Adverse Events
(CTCAE) Grade 2

- Unwilling or unable to undergo a magnetic resonance imaging (MRI) or computed
tomography (CT) scan

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- Darlinghurst
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- Parkville
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- Saint Leonards
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- Brisbane
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- Herston
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- Adelaide
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- Bedford Park
Recruitment hospital [8] 0 0
- Frankston
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- Melbourne
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- Perth
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- Darlinghurst
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- Parkville
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- Saint Leonards
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- Brisbane
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- Herston
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- Adelaide
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- Bedford Park
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- Frankston
Recruitment postcode(s) [9] 0 0
- Melbourne
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- Perth
Recruitment outside Australia
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Vienna
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Hainaut
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Liege
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Pleven
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Plovdiv
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Ruse
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Sofia
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Varna
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Northern Ireland
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Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sierra Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib in
participants with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential
thrombocythemia myelofibrosis (post-PV/ET MF) who have not yet received treatment with a
Janus kinase inhibitor (JAK inhibitor).

Participants will be randomized to receive either MMB or ruxolitinib for 24 weeks during a
double-blind treatment phase, after which they will be eligible to receive open-label MMB for
up to an additional 216 weeks. After discontinuation of study medication, assessments will
continue for 12 additional weeks, after which participants will be contacted for survival
follow-up approximately every 6 months for up to 5 years from the date of enrollment or until
study termination. For those participants planning to continue treatment with MMB following
the end of the study, the Early Study Drug Discontinuation (ESDD), 30-day, 12-Week, and
survival follow-up visits are not required.
Trial website
https://clinicaltrials.gov/show/NCT01969838
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications