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/show/NCT01437787




Registration number
NCT01437787
Ethics application status
Date submitted
16/09/2011
Date registered
21/09/2011
Date last updated
8/01/2016

Titles & IDs
Public title
Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis
Scientific title
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
Secondary ID [1] 0 0
2011-001897-25
Secondary ID [2] 0 0
EFC12153
Universal Trial Number (UTN)
Trial acronym
JAKARTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematopoietic Neoplasm 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR302503
Treatment: Drugs - Placebo

Placebo Comparator: Placebo comparator - once daily X 28 days, orally, empty stomach, approximately same time each day

Experimental: SAR302503 400 mg - once daily X 28 days, orally, empty stomach, approximately same time each day

Experimental: SAR302503 500 mg - once daily X 28 days, orally, empty stomach, approximately same time each day


Treatment: Drugs: SAR302503
Pharmaceutical form:capsule
Route of administration: oral

Treatment: Drugs: Placebo
Pharmaceutical form:capsule
Route of administration: oral

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

Outcomes
Primary outcome [1] 0 0
Response Rate (RR), defined as the proportion of patients who have a =35% reduction in volume of spleen size at the end of Cycle 6, and confirmed 4 weeks thereafter
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Symptom Response Rate (SRR): Proportion of patients with =50% reduction from baseline to the end of Cycle 6 in the total symptom score. - This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.
Timepoint [2] 0 0
approximately 5 years
Secondary outcome [3] 0 0
PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.
Timepoint [3] 0 0
approximately 5 years
Secondary outcome [4] 0 0
Proportion of patients who have =25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter.
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI.
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Clinical and laboratory events graded by the NCI CTCAE v4.03.
Timepoint [6] 0 0
approximately 5 years

Eligibility
Key inclusion criteria
Inclusion criteria:

- Diagnosis of Primary Myelofibrosis (MF) or Post-Polycythemia Vera MF or Post-Essential
Thrombocythemia MF, according to the 2008 World Health Organization and International
Working Group of Myelofibrosis Research and Treatment (IWG-MRT) criteria.

- MF classified as high-risk or intermediate-risk level 2, as defined by modified
IWG-MRT criteria (IPSS) (according to Cervantes F. et. al.; at screening).

- Enlarged spleen, palpable at least 5 cm below costal margin.

- At least 18 years of age.

- Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at study entry.

- The following laboratory values within 14 days prior to the initiation of IMP or
placebo:

- Absolute Neutrophil Count (ANC) =1.0 x 10exp9/L

- Platelet count =50 x 10exp9/L

- Serum creatinine =1.5 x Upper Limit of Normal (ULN)

- Serum amylase and lipase =1.5 x ULN
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Splenectomy.

- Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide,
interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day
prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones
(eg, androgens, danazol) within 14 days prior to initiation of IMP or placebo;
darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who
have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the
study as long as it has not been administered within 14 days prior to initiation of
IMP or placebo.

- Major surgery within 28 days or radiation within 6 months prior to initiation of IMP
or placebo.

- Prior treatment with a Janus Kinase 2 (JAK2) inhibitor.

- Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers

- AST or ALT =2.5 x ULN

- Total Bilirubin:

- Exclude if =3.0 x ULN

- Patients with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct
bilirubin fraction is =25% of the total

- Prior history of chronic liver disease (eg, chronic alcoholic liver disease,
autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,
hemachromatosis, non-alcoholic steatohepatitis [NASH])

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.

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 analysing the results/data
Intervention assignment
Crossover
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)
Recruitment hospital [1] 0 0
Investigational Site Number 036001 - Box Hill
Recruitment hospital [2] 0 0
Investigational Site Number 036005 - Herston
Recruitment hospital [3] 0 0
Investigational Site Number 036003 - Randwick
Recruitment hospital [4] 0 0
Investigational Site Number 036004 - Tweed Heads
Recruitment hospital [5] 0 0
Investigational Site Number 036002 - Wodonga
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [5] 0 0
3690 - Wodonga
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
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Austria
State/province [8] 0 0
Wien
Country [9] 0 0
Belgium
State/province [9] 0 0
Antwerpen
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
Jau
Country [12] 0 0
Brazil
State/province [12] 0 0
Porto Alegre
Country [13] 0 0
Brazil
State/province [13] 0 0
Rio De Janeiro
Country [14] 0 0
Canada
State/province [14] 0 0
Montreal
Country [15] 0 0
Canada
State/province [15] 0 0
Saint John
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Nantes Cedex 01
Country [18] 0 0
France
State/province [18] 0 0
Nimes
Country [19] 0 0
France
State/province [19] 0 0
Pierre Benite Cedex
Country [20] 0 0
France
State/province [20] 0 0
Poitiers
Country [21] 0 0
France
State/province [21] 0 0
Toulouse
Country [22] 0 0
France
State/province [22] 0 0
Villejuif Cedex
Country [23] 0 0
Germany
State/province [23] 0 0
Aachen
Country [24] 0 0
Germany
State/province [24] 0 0
Bonn
Country [25] 0 0
Germany
State/province [25] 0 0
Dresden
Country [26] 0 0
Germany
State/province [26] 0 0
Mannheim
Country [27] 0 0
Hungary
State/province [27] 0 0
Budapest
Country [28] 0 0
Hungary
State/province [28] 0 0
Debrecen
Country [29] 0 0
Hungary
State/province [29] 0 0
Györ
Country [30] 0 0
Hungary
State/province [30] 0 0
Kecskemét
Country [31] 0 0
Hungary
State/province [31] 0 0
Miskolc
Country [32] 0 0
Ireland
State/province [32] 0 0
Dublin
Country [33] 0 0
Ireland
State/province [33] 0 0
Galway
Country [34] 0 0
Israel
State/province [34] 0 0
Haifa
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Hashomer
Country [36] 0 0
Italy
State/province [36] 0 0
Bergamo
Country [37] 0 0
Italy
State/province [37] 0 0
Bologna
Country [38] 0 0
Italy
State/province [38] 0 0
Firenze
Country [39] 0 0
Italy
State/province [39] 0 0
Pavia
Country [40] 0 0
Italy
State/province [40] 0 0
Varese
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Bundang-Gu
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Lithuania
State/province [43] 0 0
Kaunas
Country [44] 0 0
Lithuania
State/province [44] 0 0
Klaipeda
Country [45] 0 0
Mexico
State/province [45] 0 0
Queretaro
Country [46] 0 0
Poland
State/province [46] 0 0
Brzozow
Country [47] 0 0
Poland
State/province [47] 0 0
Gdansk
Country [48] 0 0
Poland
State/province [48] 0 0
Lodz
Country [49] 0 0
Poland
State/province [49] 0 0
Warszawa
Country [50] 0 0
Poland
State/province [50] 0 0
Wroclaw
Country [51] 0 0
Portugal
State/province [51] 0 0
Coimbra
Country [52] 0 0
Portugal
State/province [52] 0 0
Lisboa
Country [53] 0 0
Portugal
State/province [53] 0 0
Porto
Country [54] 0 0
Romania
State/province [54] 0 0
Brasov
Country [55] 0 0
Romania
State/province [55] 0 0
Bucharest
Country [56] 0 0
Romania
State/province [56] 0 0
Bucuresti
Country [57] 0 0
Romania
State/province [57] 0 0
Timisoara
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Moscow
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Nizhny Novgorod
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Petrozavodsk
Country [61] 0 0
Russian Federation
State/province [61] 0 0
St-Petersburg
Country [62] 0 0
Russian Federation
State/province [62] 0 0
St.-Petersburg
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Volgograd
Country [64] 0 0
Singapore
State/province [64] 0 0
Singapore
Country [65] 0 0
South Africa
State/province [65] 0 0
Johannesburg
Country [66] 0 0
South Africa
State/province [66] 0 0
Parktown
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Sweden
State/province [69] 0 0
Stockholm
Country [70] 0 0
Sweden
State/province [70] 0 0
Uddevalla
Country [71] 0 0
Taiwan
State/province [71] 0 0
Changhua
Country [72] 0 0
Taiwan
State/province [72] 0 0
Kaohsiung
Country [73] 0 0
Taiwan
State/province [73] 0 0
Taipei
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Belfast
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Birmingham
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Glasgow
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Leeds
Country [78] 0 0
United Kingdom
State/province [78] 0 0
London
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Manchester
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Newcastle Upon Tyne
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Oxford
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

- To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503
(Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen
volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in
patients with contraindications for MRI).

Secondary Objectives:

- To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as
measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.

- To evaluate the Overall Survival of patients treated with either 400 mg/day or 500
mg/day of IMP as compared to placebo.

- To evaluate the Progression Free Survival of patients treated with either 400 mg/day or
500 mg/day of IMP as compared to placebo.

- To evaluate the durability of splenic response.

- To evaluate the safety of IMP.
Trial website
https://clinicaltrials.gov/show/NCT01437787
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
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