Last updated on July 2019

INCB 18424-272 A Double-Blind, Double-Dummy Phase 2 Randomized Study to Evaluate the Efficacy and Safety of Ruxolitinib Versus Anagrelide in Subjects with Essential Thrombocythemia Who are Resistant to or Intolerant of Hydroxyurea


Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: *Healthy Patient Studies
  • Age: 18 Years
  • Gender: Male or Female

A subject who meets all of the following criteria may be included in the study:

  1. Men and women, aged 18 or older.
  2. Subjects diagnosed with ET according to revised WHO 2016 criteria (Appendix A; Arber et al 2016).
  3. Subjects who are resistant to or intolerant of HU (Appendix B), that is, fulfilling at least 1 of the following criteria:
    1. Platelet count > 600× 109/L after 3 months of at least 2 g/day of HU (2.5 g/day in subjects with a body weight over 80 kg) OR at the subject's maximally tolerated dose if that dose is < 2 g/day.
    2. Platelet count > 400 × 109/L and WBC count < 2.5 × 109/L or hemoglobin (Hgb) > 10 g/dl at any dose of HU.
    3. Presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU.
    4. HU-related fever.
  4. Platelet count > 650 × 109/L at screening.
  5. WBC > 11.0 × 109/L at screening.
  6. ECOG performance status 0 to 2.
  7. Known status of JAKV617F mutation.
  8. Willingness to avoid pregnancy or fathering children based on the following criteria (Appendix G):
    1. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR = 12 months of amenorrhea and at least 50 years of age).
    2. Woman of childbearing potential who has a negative serum pregnancy test at screening and negative urinary test before the first dose on Day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.
    3. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.

Subject Exclusion Criteria

A subject who meets any of the following criteria will be excluded from the study:
  1. Subjects who have previously been treated with anagrelide or JAK inhibitors.
  2. Subjects with inadequate liver function at screening and Day 1 (before drug administration) as demonstrated by the following:
    1. Total bilirubin > 1.5 × ULN.
    2. AST or ALT > 1.5 × ULN.
    3. Hepatocellular disease (eg, cirrhosis).
  3. Subjects with inadequate renal function at screening as demonstrated by creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
  4. Subjects with clinically significant cardiovascular disease, including uncontrolled cardiac disease, including unstable angina; acute myocardial infarction within 6 months from Day 1 of study drug administration; New York Heart Association Class III or IV congestive heart failure; and arrhythmia requiring therapy unless approved by medical monitor/sponsor.
  5. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
  6. Subjects with impairment of gastrointestinal (GI) function or active GI disease that may significantly alter absorption of ruxolitinib or anagrelide (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, and small bowel obstruction).
  7. Inability to swallow and retain oral medication.
  8. Subjects with clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy:
    1. Subjects with acute bacterial infections requiring antibiotic therapy should delay screening/enrollment until the course of antibiotic therapy has been completed.
    2. Subjects on chronic antibiotics for prophylaxis are allowed.
  9. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation: HBV DNA and HCV RNA must be undetectable. Subjects cannot be positive for hepatitis B surface antigen or anti–hepatitis B core antibodies. Subjects who have positive anti-HBs as the only evidence of prior exposure may participate in the study provided that there is both 1) no known history of HBV infection and 2) verified receipt of hepatitis B vaccine.
  10. Known human immunodeficiency virus infection.
  11. Subjects with diagnosed primary immunodeficiency syndromes, such as X-linked gammaglobulinemia and common variable immune deficiency.
  12. Subjects with peripheral blood blast count of > 0% at screening.
  13. Subjects with an active malignancy over the previous 2 years except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or completely resected papillary thyroid and follicular thyroid cancers.
  14. Pregnant or breastfeeding women.
  15. Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of ruxolitinib or anagrelide or their anticipated use during the study (does not apply to topical ketoconazole).
  16. Use of concomitant treatment of fluconazole at a dose > 200 mg.
  17. Subjects being treated concurrently with any prohibited medications.
  18. Subjects being treated concurrently with any medications that may prolong QTc interval of the ECG (including but not limited to chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amodarone, disopyramide, procainamide, and pimozide).
  19. Subjects being treated concurrently with any investigational agent or who have previously participated in an investigational study within 30 days before to the first dose of study drug or within 5 half-lives of the previous investigational product, whichever is longer (except for treatment with HU that can be stopped the day before the first day of dosing with study treatment).
  20. Subjects being treated concurrently with any investigational agent or who have previously participated in an investigational study within 30 days before to the first dose of study drug or within 5 half-lives of the previous investigational product, whichever is longer (excepting for treatment with HU that can be stopped the day before the first day of dosing with study treatment).
  21. Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF).
  22. Subjects who are unwilling or incapable of complying with the requirements of the study.
  23. Subjects with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
  24. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
  25. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


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