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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Polycythemia Vera Symptom Study Evaluating Ruxolitinib Versus Hydroxyurea in a Randomized, Multicenter, Double-Blind, Double-Dummy, Phase 3 Efficacy and Safety Study of Patient Reported Outcomes

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Hydroxyurea (HU)
* Drug: HU-placebo
* Drug: Ruxolitinib-placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ruxolitinib and hydroxyurea (HU)-placebo<br> | Drug: Ruxolitinib<br>* Ruxolitinib will be orally self-administered at a starting dose of 10 mg (two 5 mg tablets) twice a day. Dose increases of 5 mg (1 tablet) in twice-daily increments are permitted after 4 weeks and again after 8 weeks of therapy for subjects who meet prespecified criteria for inadequate efficacy.<br>Drug: HU-placebo<br>* All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the ruxolitinib dose, the dose of HU-placebo will be adjusted concurrently.<br>|
| Active Comparator: HU and ruxolitinib-placebo<br> | Drug: Hydroxyurea (HU)<br>* Hydroxyurea (500 mg capsules) will be orally self-administered at the dose that the subject was receiving previously. The dose may be increased after 4 weeks and again after 8 weeks of therapy to optimize efficacy for subjects meeting prespecified criteria.<br>Drug: Ruxolitinib-placebo<br>* All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the HU dose, the dose of ruxolitinib-placebo will be adjusted concurrently.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | From Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake. | From Baseline to Week 16 | 
| 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 | 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 | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycythemia Vera, PV