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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01632904
First received: June 29, 2012
Last updated: May 14, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Polycythemia Vera
Drug: Ruxolitinib
Drug: Hydroxyurea (HU)
Drug: HU-placebo
Drug: Ruxolitinib-placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • 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 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    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:
  • Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 [ Time Frame: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake.

  • Percentage of Subjects Achieving a Durable Response on TSS-C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Durable Response on TSS-C defined as a ≥ 50% improvement from baseline in TSS-C at Week 16 that was maintained at the Week 48 visit.

  • Percentage of Subjects Achieving a Durable Response on Individual Symptoms Scores for TSS-C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: June 2012
Study Completion Date: November 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ruxolitinib and hydroxyurea (HU)-placebo Drug: Ruxolitinib
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.
Drug: HU-placebo

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.

Active Comparator: HU and ruxolitinib-placebo Drug: Hydroxyurea (HU)
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.
Drug: Ruxolitinib-placebo

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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01632904

  Show 70 Study Locations
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Mark Jones, M.D. Incyte Corporation
  More Information

No publications provided

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01632904     History of Changes
Other Study ID Numbers: 18424-357
Study First Received: June 29, 2012
Results First Received: March 26, 2015
Last Updated: May 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Incyte Corporation:
Polycythemia Vera
PV

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015