Switch Study From Hydroxyurea to Ruxolitinib for RELIEF of Polycythemia Vera Symptoms: The Relief Study

• Proportion of subjects with ≥ 50% reduction in individual PV-related symptoms at Week 16 compared to Baseline [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
• Duration of symptomatic improvement in subjects experiencing relief from the cluster of PV-related symptoms [ Time Frame: Week 16 and Week 48. ] [ Designated as safety issue: No ]
• Duration of symptomatic improvement in subjects experiencing relief from individual symptoms [ Time Frame: Week 16 and Week 48. ] [ Designated as safety issue: No ]
• Safety of ruxolitinib and HU as measured by adverse events. [ Time Frame: Screening through the end of study participation (estimated 18 months). ] [ Designated as safety issue: Yes ]

The purpose of the RELIEF study is to compare symptoms in polycythemia vera (PV) subjects treated with ruxolitinib versus subjects treated with hydroxyurea (HU) as measured by the percent of subjects who achieve a clinically meaningful symptom improvement (ie, total symptom score reduction of ≥ 50% reduction) at Week 16 compared to Baseline. The study is also designed to demonstrate that these responses are durable with continued treatment.

This is a Phase 3 multicenter, double-blind, double-dummy, randomized study. Only subjects with PV who have received HU for at least 12 weeks, have been receiving a stable dose before screening and still have symptoms related to PV will be enrolled.

Subjects will be randomized (1:1) to 1 of 2 treatment arms:

A: ruxolitinib and HU-placebo B: HU and ruxolitinib-placebo

Subjects randomized to either arm may be eligible to transition to open-label ruxolitinib after Week 16.

• Drug: ruxolitinib and HU-placebo
  All subjects begin on 10mg BID of ruxolitinib or its placebo based on randomization assignment. NOTE: Subjects who are randomized to ruxolitinib 10mg BID will also receive HU-placebo.
• Drug: HU and ruxolitinib-placebo
  All subjects begin on the stable pre-study dose of HU or its placebo based on randomization assignment. NOTE: Subjects randomized to HU will also receive ruxolitinib-placebo.

• Experimental: ruxolitinib and HU-placebo
  Intervention: Drug: ruxolitinib and HU-placebo
• Active Comparator: HU and ruxolitinib-placebo
  Intervention: Drug: HU and ruxolitinib-placebo

Inclusion Criteria:

• Subjects must currently be reporting symptoms while on a stable dose of HU monotherapy and be eligible to continue HU on study after randomization.
• Before screening, the subject must have been receiving HU for at least 12 weeks AND be receiving a stable dose.
• Subjects must meet baseline symptom criteria

• Subjects should meet at least 1 of the following criteria:

  • No more than 1 phlebotomy within the 6 months before screening OR
  • No palpable splenomegaly.
• Subjects must have a hematocrit that can be controlled within 35% to 48% (inclusive) before randomization.

Exclusion Criteria:

• Subjects with inadequate liver or renal function at screening.
• Subjects with clinically significant infection that requires therapy
• Subjects with known active hepatitis A, B, or C at screening or with known HIV positivity.
• Subjects with an active malignancy over the previous 2 years
• Subjects with clinically significant cardiac disease (Class III or IV).