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/NCT01420783




Registration number
NCT01420783
Ethics application status
Date submitted
11/08/2011
Date registered
22/08/2011
Date last updated
17/03/2016

Titles & IDs
Public title
Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia
Scientific title
A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea
Secondary ID [1] 0 0
2011-001847-58
Secondary ID [2] 0 0
ARD12042
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematopoietic Neoplasm 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

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

Experimental: SAR302503 100 mg - once daily X 28 days

Experimental: SAR302503 200 mg - once daily X 28 days

Experimental: SAR302503 400 mg - once daily X 28 days

Experimental: SAR302503 600 mg - once daily X 28 days


Treatment: Drugs: SAR302503
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
Dose Ranging Phase: Proportion of PV patients with absence of phlebotomy and hematocrit below 45% and proportion of ET patients with a platelet count = 400 x 10x9/L for a minimum of 3 months during the first 8 cycles of therapy.
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
PV Dose Expansion Phase: Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.
Timepoint [2] 0 0
2 years
Primary outcome [3] 0 0
ET Dose Ranging Phase (only 600 mg dose group): Proportion of ET patients with a platelet count =400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.
Timepoint [3] 0 0
2 years
Secondary outcome [1] 0 0
Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit through Cycle 8 (for PV dose expansion phase only).
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Proportion of ET patients with platelet count =400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Cycle 8.
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Characterization of clinicohematologic response (CR, PR, and no Response) defined by European LeukemiaNet beginning at Day 1 of Cycle 6 visit through Cycle 8.
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Proportion of patients with a = 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Number of participants who have changes in histological, cytogenetic, and molecular responses in bone marrow.
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Response (defined as either a 2-point improvement in or resolution of a symptom present at baseline) at the end of Cycles 1, 4, and 8 or end of treatment (EOT), as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Cumulative Distribution Function of responses between treatment groups at the end of Cycles 1, 4, and 8 or EOT on the MPN-SAF.
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
For each MPN-associated symptom present at baseline on the MPN-SAF, proportion of patients with resolution of that symptom at the end of Cycles 1, 4, and 8.
Timepoint [9] 0 0
2 years
Secondary outcome [10] 0 0
To measure generic health-related quality of life and utility values using the EQ-5D questionnaire after completion of 8 cycles of therapy.
Timepoint [10] 0 0
2 years
Secondary outcome [11] 0 0
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) - CTCAE version 4.03, clinical laboratory parameters, ECG, and vital signs.
Timepoint [11] 0 0
2 years

Eligibility
Key inclusion criteria
Inclusion criteria:

- Has had a diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or
essential thrombocythemia (ET) documented at Screening.

- Polycythemia vera or essential thrombocythemia defined according to the revised WHO
criteria.

- Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia
vera patients on hydroxyurea with a hematocrit >45%, or phlebotomy twice in the last 6
months and at least once in the last 3 months.

- Essential thrombocythemia resistance or intolerance to hydroxurea is defined as
essential thrombocythemia patients on HU with platelet count >600 x 10x9/L.

Dose Expansion Phase (polycythemia vera) and 600 mg/day group (essential thrombocythemia):

- Has had a diagnosis of polycythemia vera or essential thrombocythemia according to the
revised WHO 2008 criteria.

- PV patients must be resistant or intolerant to hydroxyurea.

- ET patients must be resistant or intolerant to hydroxyurea.

- Provide written informed consent to participate.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Less than 18 years of age.

- Participation in any study of an investigational agent (drug, biologic, device) within
30 days prior to initiation of study drug, unless during non-treatment phase. (Prior
treatment with another JAK2 inhibitor is allowed.)

- Unwilling to comply with scheduled visits, treatment plans, laboratory assessments,
and other study-related procedures.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4 at study
entry.

- Splenectomy.

- Active malignancy other than polycythemia vera or essential thrombocythemia, except
adequately treated basal cell carcinoma and squamous cell carcinoma of the skin,
cervical carcinoma in situ, or other malignancies that have been stable and off
therapy for =5 years.

- Major surgery within 28 days or radiation within 3 months prior to initiation of study
drug.

- Active acute infection requiring antibiotics.

- Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
illness.

- Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
artery bypass surgery, transient ischemic attack, or pulmonary embolism within 3
months prior to initiation of study drug.

- Any severe acute or chronic medical, neurological, or psychiatric condition or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration, may interfere with the informed consent process and/or
with compliance with the requirements of the study, or may interfere with
interpretation of study results and, in the Investigator's opinion, would make the
patient inappropriate for entry into this study.

- Inadequate organ function.

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

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

- Concomitant treatment with or use of drugs or herbal agents known to be at least
moderate inhibitors or inducers cytochrome P450 3A4 (CYP3A4).

- Presence of any gastric or other disorder that would inhibit absorption of oral
medication.

- Known hypersensitivity to any excipients in the study drug formulation.

- Women of childbearing potential, unless using effective contraception while on study
drug.

- Men who partner with a woman of childbearing potential, unless they agree to use
effective contraception while on study drug.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
1/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2014
Sample size
Target
Accrual to date
Final
81
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036001 - Clayton
Recruitment hospital [2] 0 0
Investigational Site Number 036002 - Kingswood
Recruitment hospital [3] 0 0
Investigational Site Number 036004 - Kogarah
Recruitment hospital [4] 0 0
Investigational Site Number 036003 - Randwick
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2031 - Randwick
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
Michigan
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
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Canada
State/province [7] 0 0
Montreal
Country [8] 0 0
Canada
State/province [8] 0 0
Toronto
Country [9] 0 0
Canada
State/province [9] 0 0
Vancouver
Country [10] 0 0
France
State/province [10] 0 0
Brest
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Paris Cedex 10
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt Am Main
Country [14] 0 0
Germany
State/province [14] 0 0
Mannheim
Country [15] 0 0
Italy
State/province [15] 0 0
Bologna
Country [16] 0 0
Italy
State/province [16] 0 0
Firenze
Country [17] 0 0
Italy
State/province [17] 0 0
Orbassano
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seongnam
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Spain
State/province [20] 0 0
Badalona
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Belfast
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Birmingham
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

- Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg
SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per
European LeukemiaNet criteria) for :

- Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months
in patients with polycythemia vera, and

- Reduction of platelet count to =400 x 10x9/L for a minimum of 3 months in patients
with essential thrombocythemia.

- PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate
the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or
intolerant to hydroxyurea (per European LeukemiaNet criteria) for:

- Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and
continuing through Day 1 of Cycle 6 visit in patients with PV, and

- Reduction of platelet count to =400 x 10x9/L beginning at Day 1 of Cycle 4 visit
and continuing through Day 1 of Cycle 6 visit in patients with ET.

Secondary Objectives:

- To evaluate the safety of SAR302503.

- To evaluate the efficacy of SAR302503 in patients with PV who are resistant or
intolerant to hydroxyurea for inducing absence of phlebotomy eligibility.

- To evaluate the efficacy of SAR302503 in patients with ET who are resistant or
intolerant to hydroxyurea for reduction of platelet counts.

- To evaluate the efficacy of SAR302503 in inducing complete and partial responses
beginning at Day 1 of Cycle 6 visit through Cycle 8.

- To evaluate splenic response as measured by spleen volume using MRI or CT.

- To evaluate the pharmacokinetics of SAR302503 after single and repeat doses.

- To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele
burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition.

- To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated
symptoms, as well as overall impact on quality of life.

- To measure generic health-related quality of life and utility value using the EuroQol
Group (EQ-5DTM) questionnaire.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01420783
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01420783