Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis

Hematopoietic Neoplasm Clinical Trial

— JAKARTA  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01437787
• Other study ID #: EFC12153
• Secondary ID: 2011-001897-25U1
• Status: Completed
• Phase: Phase 3
• First received: September 16, 2011
• Last updated: December 8, 2015
• Start date: December 2011
• Est. completion date: June 2014

Study information

• Verified date: December 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

The expected duration of a patient's treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a ≥6-month (6-cycle) treatment period, and an End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematopoietic Neoplasm
• Primary Myelofibrosis

Intervention

Drug:
• SAR302503
Pharmaceutical form:capsule Route of administration: oral
• Placebo
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
Australia	Investigational Site Number 036001	Box Hill
Australia	Investigational Site Number 036005	Herston
Australia	Investigational Site Number 036003	Randwick
Australia	Investigational Site Number 036004	Tweed Heads
Australia	Investigational Site Number 036002	Wodonga
Austria	Investigational Site Number 040001	Wien
Belgium	Investigational Site Number 056003	Antwerpen
Belgium	Investigational Site Number 056001	Leuven
Brazil	Investigational Site Number 076002	Jau
Brazil	Investigational Site Number 076004	Porto Alegre
Brazil	Investigational Site Number 076001	Rio De Janeiro
Canada	Investigational Site Number 124001	Montreal
Canada	Investigational Site Number 124003	Montreal
Canada	Investigational Site Number 124002	Saint John
France	Investigational Site Number 250006	Marseille
France	Investigational Site Number 250005	Nantes Cedex 01
France	Investigational Site Number 250004	Nimes
France	Investigational Site Number 250002	Pierre Benite Cedex
France	Investigational Site Number 250007	Poitiers
France	Investigational Site Number 250003	Toulouse
France	Investigational Site Number 250001	Villejuif Cedex
Germany	Investigational Site Number 276006	Aachen
Germany	Investigational Site Number 276007	Bonn
Germany	Investigational Site Number 276008	Dresden
Germany	Investigational Site Number 276001	Mannheim
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348001	Debrecen
Hungary	Investigational Site Number 348007	Györ
Hungary	Investigational Site Number 348006	Kecskemét
Hungary	Investigational Site Number 348003	Miskolc
Ireland	Investigational Site Number 372002	Dublin
Ireland	Investigational Site Number 372001	Galway
Israel	Investigational Site Number 376003	Haifa
Israel	Investigational Site Number 376002	Tel Hashomer
Italy	Investigational Site Number 380002	Bergamo
Italy	Investigational Site Number 380007	Bologna
Italy	Investigational Site Number 380004	Firenze
Italy	Investigational Site Number 380001	Pavia
Italy	Investigational Site Number 380006	Pavia
Italy	Investigational Site Number 380003	Varese
Korea, Republic of	Investigational Site Number 410002	Bundang-Gu
Korea, Republic of	Investigational Site Number 410001	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Korea, Republic of	Investigational Site Number 410004	Seoul
Korea, Republic of	Investigational Site Number 410005	Seoul
Korea, Republic of	Investigational Site Number 410006	Seoul
Korea, Republic of	Investigational Site Number 410007	Seoul
Lithuania	Investigational Site Number 440001	Kaunas
Lithuania	Investigational Site Number 440002	Klaipeda
Mexico	Investigational Site Number 484001	Queretaro
Poland	Investigational Site Number 616005	Brzozow
Poland	Investigational Site Number 616002	Gdansk
Poland	Investigational Site Number 616006	Lodz
Poland	Investigational Site Number 616010	Warszawa
Poland	Investigational Site Number 616003	Wroclaw
Portugal	Investigational Site Number 620005	Coimbra
Portugal	Investigational Site Number 620001	Lisboa
Portugal	Investigational Site Number 620004	Lisboa
Portugal	Investigational Site Number 620003	Porto
Romania	Investigational Site Number 642003	Brasov
Romania	Investigational Site Number 642004	Bucharest
Romania	Investigational Site Number 642002	Bucuresti
Romania	Investigational Site Number 642006	Bucuresti
Romania	Investigational Site Number 642001	Timisoara
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643009	Moscow
Russian Federation	Investigational Site Number 643010	Nizhny Novgorod
Russian Federation	Investigational Site Number 643008	Petrozavodsk
Russian Federation	Investigational Site Number 643004	St-Petersburg
Russian Federation	Investigational Site Number 643005	St.-Petersburg
Russian Federation	Investigational Site Number 643007	Volgograd
Singapore	Investigational Site Number 702001	Singapore
Singapore	Investigational Site Number 702002	Singapore
South Africa	Investigational Site Number 710003	Johannesburg
South Africa	Investigational Site Number 710002	Parktown
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724002	Madrid
Sweden	Investigational Site Number 752001	Stockholm
Sweden	Investigational Site Number 752002	Uddevalla
Taiwan	Investigational Site Number 158002	Changhua
Taiwan	Investigational Site Number 158003	Kaohsiung
Taiwan	Investigational Site Number 158001	Taipei
United Kingdom	Investigational Site Number 826006	Belfast
United Kingdom	Investigational Site Number 826003	Birmingham
United Kingdom	Investigational Site Number 826002	Glasgow
United Kingdom	Investigational Site Number 826004	Leeds
United Kingdom	Investigational Site Number 826001	London
United Kingdom	Investigational Site Number 826005	London
United Kingdom	Investigational Site Number 826007	Manchester
United Kingdom	Investigational Site Number 826008	Newcastle Upon Tyne
United Kingdom	Investigational Site Number 826009	Oxford
United Kingdom	Investigational Site Number 826010	Southampton
United States	Investigational Site Number 840013	Baton Rouge	Louisiana
United States	Investigational Site Number 840002	Canton	Ohio
United States	Investigational Site Number 840004	Houston	Texas
United States	Investigational Site Number 840001	La Jolla	California
United States	Investigational Site Number 840012	La Jolla	California
United States	Investigational Site Number 840006	Los Angeles	California
United States	Investigational Site Number 840009	Newark	New Jersey
United States	Investigational Site Number 840008	Rochester	Minnesota
United States	Investigational Site Number 840014	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		6 months	No
Secondary	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.	6 months	No
Secondary	OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.		approximately 5 years	No
Secondary	PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.		approximately 5 years	No
Secondary	Proportion of patients who have =25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter.		6 months	No
Secondary	Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI.		2 years	No
Secondary	Clinical and laboratory events graded by the NCI CTCAE v4.03.		approximately 5 years	Yes