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

Phase 3

Completed

Interventions: Drug: Hydroxyurea (HU)
Drug: Ruxolitinib
Drug: Ruxolitinib-placebo
Drug: HU-placebo

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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 2 phlebotomies 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).

Arm && Interventions

Group	Intervention	Description
HU and ruxolitinib-placebo	Hydroxyurea (HU)	-
HU and ruxolitinib-placebo	Ruxolitinib-placebo	-
ruxolitinib and hydroxyurea (HU)-placebo	Ruxolitinib	-
ruxolitinib and hydroxyurea (HU)-placebo	HU-placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving a ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine (TSS-C) at Week 16, as Measured by the Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Diary	From Baseline to Week 16	Symptoms of polycythemia vera were assessed using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) electronic diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): tiredness, itching, muscle aches, night sweats, and sweats while awake. The total symptom score ranged from 0-50 and was calculated as the sum of the 5 symptom scores. A higher score indicates worse symptoms.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16	From Baseline to Week 16	The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake.
Proportion of Subjects Randomized to Ruxolitinib Who Achieved ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine and the Individual Symptom Scores at Week 16 That Were Maintained at Week 48	Week 48	Durable Response on TSS-C/individual symptoms defined as a ≥ 50% reduction in TSS-C/individual symptoms at Week 16 that were maintained at Week 48