Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01969838




Registration number
NCT01969838
Ethics application status
Date submitted
22/10/2013
Date registered
25/10/2013
Date last updated
12/05/2023

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
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Total Symptom Score (TSS) Response Rate at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Rate of Red Blood Cell (RBC) Transfusions in the Double-blind Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)
Timepoint [2] 0 0
Baseline to Week 24
Secondary outcome [3] 0 0
RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding)
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
RBC Transfusion Dependence Rate at Week 24. (Defined as Having Had at Least 4 Units of RBC Transfusions, or a Hemoglobin Level Below 8 g/dL in 8 Weeks Prior to Week 24 (Excluding Cases Associated With Clinically Overt Bleeding)).
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
Sex
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
6/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/05/2019
Sample size
Target
Accrual to date
Final
432
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Parkville
Recruitment hospital [3] 0 0
- Saint Leonards
Recruitment hospital [4] 0 0
- Brisbane
Recruitment hospital [5] 0 0
- Herston
Recruitment hospital [6] 0 0
- Adelaide
Recruitment hospital [7] 0 0
- Bedford Park
Recruitment hospital [8] 0 0
- Frankston
Recruitment hospital [9] 0 0
- Melbourne
Recruitment hospital [10] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- Saint Leonards
Recruitment postcode(s) [4] 0 0
- Brisbane
Recruitment postcode(s) [5] 0 0
- Herston
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Bedford Park
Recruitment postcode(s) [8] 0 0
- Frankston
Recruitment postcode(s) [9] 0 0
- Melbourne
Recruitment postcode(s) [10] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Austria
State/province [11] 0 0
Vienna
Country [12] 0 0
Belgium
State/province [12] 0 0
Hainaut
Country [13] 0 0
Belgium
State/province [13] 0 0
Antwerp
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Belgium
State/province [15] 0 0
Liege
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Pleven
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Plovdiv
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Ruse
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Sofia
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Varna
Country [21] 0 0
Canada
State/province [21] 0 0
Alberta
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Czechia
State/province [24] 0 0
Vychodocesky KRAJ
Country [25] 0 0
Czechia
State/province [25] 0 0
Brno
Country [26] 0 0
Czechia
State/province [26] 0 0
Ostrava
Country [27] 0 0
Denmark
State/province [27] 0 0
Aalborg
Country [28] 0 0
Denmark
State/province [28] 0 0
Herlev
Country [29] 0 0
France
State/province [29] 0 0
Midi-pyrenees
Country [30] 0 0
France
State/province [30] 0 0
Rhone-alpes
Country [31] 0 0
France
State/province [31] 0 0
Le Kremlin Bicetre Cedex
Country [32] 0 0
France
State/province [32] 0 0
Lens
Country [33] 0 0
France
State/province [33] 0 0
Lille Cedex
Country [34] 0 0
France
State/province [34] 0 0
Marseille Cedex 9
Country [35] 0 0
France
State/province [35] 0 0
Nantes cedex 1
Country [36] 0 0
France
State/province [36] 0 0
Paris
Country [37] 0 0
France
State/province [37] 0 0
Pessac Cedex
Country [38] 0 0
France
State/province [38] 0 0
Villejuif Cedex
Country [39] 0 0
Germany
State/province [39] 0 0
Bayern
Country [40] 0 0
Germany
State/province [40] 0 0
Sachsen
Country [41] 0 0
Germany
State/province [41] 0 0
Dresden
Country [42] 0 0
Germany
State/province [42] 0 0
Dusseldorf
Country [43] 0 0
Germany
State/province [43] 0 0
Freiburg
Country [44] 0 0
Germany
State/province [44] 0 0
Hamburg
Country [45] 0 0
Germany
State/province [45] 0 0
Mainz
Country [46] 0 0
Germany
State/province [46] 0 0
Mannheim
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
Country [48] 0 0
Hungary
State/province [48] 0 0
Debrecen
Country [49] 0 0
Hungary
State/province [49] 0 0
Kaposvár
Country [50] 0 0
Israel
State/province [50] 0 0
Afula
Country [51] 0 0
Israel
State/province [51] 0 0
Ashkelon
Country [52] 0 0
Israel
State/province [52] 0 0
Haifa
Country [53] 0 0
Israel
State/province [53] 0 0
Jerusalem
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Japan
State/province [55] 0 0
Gifu
Country [56] 0 0
Japan
State/province [56] 0 0
Hokkaido
Country [57] 0 0
Japan
State/province [57] 0 0
Osaka
Country [58] 0 0
Japan
State/province [58] 0 0
Bunkyo-ku, Tokyo
Country [59] 0 0
Japan
State/province [59] 0 0
Fukushima City
Country [60] 0 0
Japan
State/province [60] 0 0
Kumamoto City
Country [61] 0 0
Japan
State/province [61] 0 0
Matsuyama
Country [62] 0 0
Japan
State/province [62] 0 0
Okayama
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Seoul
Country [64] 0 0
Netherlands
State/province [64] 0 0
Maastricht
Country [65] 0 0
Netherlands
State/province [65] 0 0
Nijmegen
Country [66] 0 0
Netherlands
State/province [66] 0 0
Rotterdam
Country [67] 0 0
Netherlands
State/province [67] 0 0
Utrecht
Country [68] 0 0
Poland
State/province [68] 0 0
Lodzkie
Country [69] 0 0
Poland
State/province [69] 0 0
Lubelskie
Country [70] 0 0
Poland
State/province [70] 0 0
Malopolskie
Country [71] 0 0
Poland
State/province [71] 0 0
Mazowiekie
Country [72] 0 0
Poland
State/province [72] 0 0
Pomorskie
Country [73] 0 0
Poland
State/province [73] 0 0
Wielkopolskie
Country [74] 0 0
Poland
State/province [74] 0 0
Bialystok
Country [75] 0 0
Poland
State/province [75] 0 0
Brzozow
Country [76] 0 0
Poland
State/province [76] 0 0
Chorzow
Country [77] 0 0
Romania
State/province [77] 0 0
Arad
Country [78] 0 0
Romania
State/province [78] 0 0
Brasov
Country [79] 0 0
Romania
State/province [79] 0 0
Bucuresti
Country [80] 0 0
Romania
State/province [80] 0 0
Cluj-Napoca
Country [81] 0 0
Romania
State/province [81] 0 0
Iasi
Country [82] 0 0
Singapore
State/province [82] 0 0
Singapore
Country [83] 0 0
Spain
State/province [83] 0 0
Madrid
Country [84] 0 0
Spain
State/province [84] 0 0
Navarra
Country [85] 0 0
Spain
State/province [85] 0 0
Badalona
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
Country [87] 0 0
Spain
State/province [87] 0 0
Valencia
Country [88] 0 0
Spain
State/province [88] 0 0
Zaragoza
Country [89] 0 0
Sweden
State/province [89] 0 0
Skane
Country [90] 0 0
Sweden
State/province [90] 0 0
Stockholm
Country [91] 0 0
Sweden
State/province [91] 0 0
Uddevalla
Country [92] 0 0
Sweden
State/province [92] 0 0
Örebro
Country [93] 0 0
Taiwan
State/province [93] 0 0
Kaohsiung
Country [94] 0 0
United Kingdom
State/province [94] 0 0
England
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Wales
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Northern Ireland
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sierra Oncology LLC - a GSK company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib (RUX) 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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01969838