Polycythemia vera MedDRA version: 19.1 Level: LLT Classification code 10036061 Term: Polycythemia vera System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Jakavi
Product Name: ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for inclusion in this study have to meet all of the following criteria: 1. Subjects 18 years of age or older. 2. Subjects must be diagnosed with PV for at least 24 weeks prior to Screening according to the 2008 World Health Organization criteria (Table 2 in Tefferi and Vardiman, 2008; Appendix 1). 3. Subjects must have a treatment history for PV that meets the definition of resistance or intolerance to hydroxyurea (HU) by exhibiting at least one of the following five criteria (modified from Barosi et al, 2009A; Appendix 2): • HU Resistance, defined at least 12 weeks into a course of HU therapy at a dose of at least 2 grams/day OR at the subject’s maximally tolerated dose if that dose is less than 2 grams/day: a. Need for phlebotomy to keep hematocrit 400 x 109/L AND white blood cell count > 10 x 109/L, OR c. Failure to reduce splenomegaly extending greater than 10 cm below the costal margin by more than 50%, as measured by palpation. • HU Intolerance: a. Absolute neutrophil count 45% at Screening 5. Palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion 6. Subjects must have at least one of the following at Screening: a. WBC > 15 x 109/L. b. PLT > 600 x 109/L. 7. Subjects with ANC >= 1.5 x 109/L at Screening. 8. Subjects with peripheral blood blast count of 0% at Screening. 9. Subjects with an ECOG performance status of 0, 1 or 2 (Appendix 5) at Screening and Baseline. 10. Subjects on a therapeutic regimen for PV must have been on a stable dose and schedule for at least 2 weeks prior to Screening and no less than 4 weeks prior to randomization (Study Day 1). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 220
Exclusion criteria
Exclusion criteria: Subjects eligible for this study must not meet any of the following criteria: 1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception (confirmed by a positive hCG laboratory test > 5 mIU/mL) and until the termination of gestation. 2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. • Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide (Appendix 3). • Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. • Reliable contraception should be maintained throughout the study and for 5-half lives of study drug after study treatment discontinuation. XML File Identifier: R+shpvV7AIq4zBHAYQAWQbcmCFM= Page 12/24 • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: and estradiol = 2 X upper limit of laboratory normal (ULN). d. Alanine aminotransferase (ALT) > 2.5x ULN. e. MDRD-eGFR < 30 mL/min/1.73m2 or on dialysis. 4. Subjects with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 5. Subjects with clinically significant bacterial, fungal, parasitic or viral infection which requires therapy: • Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. • Subjects with known active hepatitis A, B or C at Screening or with known HIV positivity. 6. Subjects with diagnosed primary immunodeficiency syndromes such as X-Linked Agammaglobulinemia and Common Variable Immune Deficiency 7. Subjects with an active malignancy over the previous 5 years except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, with no evidence for recurrence in the past 3 years. 8. Subjects w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of INC424 to Best Available Therapy (BAT) as assessed by both the absence of phlebotomy eligibility and reduction in spleen volume. ;Secondary Objective: • To compare the proportion of subjects randomized to INC424 vs Best Available Therapy achieving both durable absence of phlebotomy eligibility and durable spleen volume reduction • To compare the proportion of subjects randomized to INC424 vs Best Available Therapy achieving complete hematologic remission ;Primary end point(s): Proportion of subjects achieving a response at Week 32, with response defined as having achieved both of the following: • The absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32, with no more than one phlebotomy eligibility occurring post-randomization and prior to the Week 8 visit; • A reduction in spleen volume as assessed by Imaging (see Section 6.2.1) = 35% from baseline at Week 32. ;Timepoint(s) of evaluation of this end point: Refer to protocol section 9.4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: Proportion of all randomized subjects who achieve the primary endpoint and who remain free from progression 48 weeks after randomization. Response Start Start of response is the date when a = 35% reduction from baseline in spleen volume as assessed by Imaging (see Section 6.2.1) was first documented, providing that response was ongoing at the time of the Week 32 spleen volume assessment. Progression (end of response) The end of response is defined as the first occurrence of either one of the following: 1. The first of two consecutive hematocrit assessments that confirms phlebotomy eligibility; 2. A spleen volume assessment by Imaging (see Section 6.2.1) that is reduced by < 35% from the baseline AND that is = 25% increased relative to the volume determined at the time of the best documented spleen volume response; 3. Death due to any cause; 4. Development of MF as evidenced by bone marrow biopsy; 5. Development of acute leukemia, as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks. ;Timepoint(s) of evaluation of this end point: refer to protocol section 9.5 | — |
Countries
Argentina, Australia, Belgium, Canada, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Spain, Thailand, Turkey, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed