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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01632904
Recruitment Status : Completed
First Posted : July 3, 2012
Results First Posted : April 7, 2015
Last Update Posted : November 14, 2017
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Polycythemia Vera
Interventions Drug: Ruxolitinib
Drug: Hydroxyurea (HU)
Drug: HU-placebo
Drug: Ruxolitinib-placebo
Enrollment 110
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ruxolitinib Hydroxyurea
Hide Arm/Group Description

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.

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.

Hydroxyurea (HU) (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.

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.

Period Title: Overall Study
Started 54 56
Completed 47 [1] 50 [2]
Not Completed 7 6
Reason Not Completed
Adverse Event             4             1
Physician Decision             0             1
Subject decision             3             2
Disease Progression             0             1
Reason for discontinuation not available             0             1
[1]
Patients still in the study as of data cutoff, 27MAR2014.
[2]
Patients still in the study as of 27MAR2014, including those who crossed over to ruxolitinib
Arm/Group Title Ruxolitinib Hydroxyurea Total
Hide Arm/Group Description

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.

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.

Hydroxyurea (HU) (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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 54 56 110
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants 56 participants 110 participants
63.1  (11.68) 64.2  (12.68) 63.7  (12.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 56 participants 110 participants
Female
30
  55.6%
22
  39.3%
52
  47.3%
Male
24
  44.4%
34
  60.7%
58
  52.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 54 participants 56 participants 110 participants
White or Caucasian 53 56 109
Asian 1 0 1
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT); all subjects randomized in the study. For the overall TSS-C score, only those subjects with a baseline score of 0 and a Week 16 score of 0 or missing were excluded from the analysis.
Arm/Group Title Ruxolitinib Hydroxyurea
Hide Arm/Group Description:

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.

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.

Hydroxyurea (HU) (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.

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.

Overall Number of Participants Analyzed 53 54
Measure Type: Number
Unit of Measure: Percentage of participants
43.4 29.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ruxolitinib, Hydroxyurea
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.82
Confidence Interval (2-Sided) 95%
0.82 to 4.04
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16
Hide Description The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake.
Time Frame From Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT); all subjects randomized in the study. For individual symptom scores within the TSS-C cluster, only those subjects with a baseline score of 0 and a Week 16 score of 0 or missing were excluded from the analysis.
Arm/Group Title Ruxolitinib Hydroxyurea
Hide Arm/Group Description:

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.

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.

Hydroxyurea (HU) (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.

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.

Overall Number of Participants Analyzed 53 54
Measure Type: Number
Unit of Measure: Percentage of participants
Tiredness (n= 50, 53) 40.0 26.4
Itching (n= 48, 50) 54.2 32.0
Muscle aches (n= 47, 49) 38.3 30.6
Night sweats (n= 42, 48) 47.6 41.7
Sweats while awake (n= 42, 46) 54.8 34.8
3.Secondary Outcome
Title 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
Hide Description 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
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT); all subjects randomized to Ruxolitinib in the study. For TSS-C/individual symptoms, subject without baseline value was excluded from the analysis.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TSS-C
31.5
(19.5 to 45.6)
Tiredness
24.1
(13.5 to 37.6)
Itching
37.0
(24.3 to 51.3)
Muscle aches
20.4
(10.6 to 33.5)
Night sweats
29.6
(18.0 to 43.6)
Sweats while awake
37.0
(24.3 to 51.3)
Time Frame The duration of the study up to Week 16. This time frame defines the blinded, comparative phase of the study where the majority of patients remained on their original randomized assignment and exposure between ruxolitinib and hydroxyurea was similar.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ruxolitinib Hydroxyurea
Hide Arm/Group Description

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.

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.

Hydroxyurea (HU) (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.

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.

All-Cause Mortality
Ruxolitinib Hydroxyurea
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Ruxolitinib Hydroxyurea
Affected / at Risk (%) Affected / at Risk (%)
Total   5/54 (9.26%)   4/56 (7.14%) 
Cardiac disorders     
Angina unstable  1  1/54 (1.85%)  0/56 (0.00%) 
General disorders     
Chest discomfort  1  1/54 (1.85%)  0/56 (0.00%) 
Pyrexia  1  0/54 (0.00%)  1/56 (1.79%) 
Infections and infestations     
Urosepsis  1  0/54 (0.00%)  1/56 (1.79%) 
Investigations     
Platelet count increased  1  1/54 (1.85%)  0/56 (0.00%) 
Hemoglobin decreased  1  0/54 (0.00%)  1/56 (1.79%) 
Metabolism and nutrition disorders     
Hyperkalemia  1  0/54 (0.00%)  1/56 (1.79%) 
Musculoskeletal and connective tissue disorders     
Spondylolisthesis  1  1/54 (1.85%)  0/56 (0.00%) 
Nervous system disorders     
Cerebral ischemia  1  1/54 (1.85%)  0/56 (0.00%) 
Renal and urinary disorders     
Hematuria  1  0/54 (0.00%)  1/56 (1.79%) 
Hydronephrosis  1  0/54 (0.00%)  1/56 (1.79%) 
Renal failure acute  1  0/54 (0.00%)  1/56 (1.79%) 
Vascular disorders     
Arterial occlusive disease  1  1/54 (1.85%)  0/56 (0.00%) 
Deep vein thrombosis  1  0/54 (0.00%)  1/56 (1.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ruxolitinib Hydroxyurea
Affected / at Risk (%) Affected / at Risk (%)
Total   50/54 (92.59%)   45/56 (80.36%) 
Blood and lymphatic system disorders     
Anemia  1  8/54 (14.81%)  5/56 (8.93%) 
Thrombocytosis  1  2/54 (3.70%)  0/56 (0.00%) 
Leukopenia  1  1/54 (1.85%)  2/56 (3.57%) 
Neutropenia  1  1/54 (1.85%)  3/56 (5.36%) 
Lymphadenopathy  1  0/54 (0.00%)  2/56 (3.57%) 
Thrombocytopenia  1  2/54 (3.70%)  5/56 (8.93%) 
Cardiac disorders     
Palpitations  1  2/54 (3.70%)  1/56 (1.79%) 
Atrial fibrillation  1  0/54 (0.00%)  2/56 (3.57%) 
Ear and labyrinth disorders     
Tinnitus  1  2/54 (3.70%)  1/56 (1.79%) 
Eye disorders     
Vision blurred  1  3/54 (5.56%)  0/56 (0.00%) 
Gastrointestinal disorders     
Nausea  1  6/54 (11.11%)  3/56 (5.36%) 
Abdominal pain upper  1  3/54 (5.56%)  0/56 (0.00%) 
Dry mouth  1  2/54 (3.70%)  0/56 (0.00%) 
Dyspepsia  1  2/54 (3.70%)  0/56 (0.00%) 
Abdominal distension  1  3/54 (5.56%)  2/56 (3.57%) 
Abdominal pain  1  3/54 (5.56%)  3/56 (5.36%) 
Vomiting  1  2/54 (3.70%)  3/56 (5.36%) 
Stomatitis  1  1/54 (1.85%)  2/56 (3.57%) 
Constipation  1  4/54 (7.41%)  7/56 (12.50%) 
Diarrhea  1  5/54 (9.26%)  11/56 (19.64%) 
General disorders     
Fatigue  1  11/54 (20.37%)  6/56 (10.71%) 
Edema peripheral  1  3/54 (5.56%)  1/56 (1.79%) 
Asthenia  1  3/54 (5.56%)  3/56 (5.36%) 
Pyrexia  1  2/54 (3.70%)  1/56 (1.79%) 
Chest pain  1  2/54 (3.70%)  0/56 (0.00%) 
Infections and infestations     
Urinary tract infection  1  4/54 (7.41%)  1/56 (1.79%) 
Upper respiratory tract infection  1  3/54 (5.56%)  2/56 (3.57%) 
Bronchitis  1  1/54 (1.85%)  2/56 (3.57%) 
Nasopharyngitis  1  1/54 (1.85%)  2/56 (3.57%) 
Injury, poisoning and procedural complications     
Contusion  1  3/54 (5.56%)  0/56 (0.00%) 
Investigations     
Weight increased  1  3/54 (5.56%)  0/56 (0.00%) 
Blood lactate dehydrogenase increased  1  2/54 (3.70%)  0/56 (0.00%) 
Neutrophil count decreased  1  0/54 (0.00%)  2/56 (3.57%) 
Weight decreased  1  0/54 (0.00%)  2/56 (3.57%) 
Platelet count decreased  1  0/54 (0.00%)  3/56 (5.36%) 
Metabolism and nutrition disorders     
Gout  1  1/54 (1.85%)  3/56 (5.36%) 
Hyperkalemia  1  0/54 (0.00%)  1/56 (1.79%) 
Hyperuricemia  1  0/54 (0.00%)  2/56 (3.57%) 
Musculoskeletal and connective tissue disorders     
Neck pain  1  2/54 (3.70%)  0/56 (0.00%) 
Muscle spasms  1  4/54 (7.41%)  3/56 (5.36%) 
Myalgia  1  2/54 (3.70%)  1/56 (1.79%) 
Arthralgia  1  2/54 (3.70%)  3/56 (5.36%) 
Back pain  1  1/54 (1.85%)  4/56 (7.14%) 
Nervous system disorders     
Headache  1  9/54 (16.67%)  3/56 (5.36%) 
Dizziness  1  7/54 (12.96%)  5/56 (8.93%) 
Paresthesia  1  2/54 (3.70%)  2/56 (3.57%) 
Psychiatric disorders     
Insomnia  1  4/54 (7.41%)  2/56 (3.57%) 
Disturbance in attention  1  2/54 (3.70%)  1/56 (1.79%) 
Depression  1  1/54 (1.85%)  3/56 (5.36%) 
Renal and urinary disorders     
Hydronephrosis  1  0/54 (0.00%)  1/56 (1.79%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/54 (0.00%)  2/56 (3.57%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  3/54 (5.56%)  1/56 (1.79%) 
Cough  1  2/54 (3.70%)  2/56 (3.57%) 
Epistaxis  1  1/54 (1.85%)  2/56 (3.57%) 
Oropharyngeal pain  1  0/54 (0.00%)  3/56 (5.36%) 
Skin and subcutaneous tissue disorders     
Rash  1  6/54 (11.11%)  0/56 (0.00%) 
Hyperhidrosis  1  4/54 (7.41%)  2/56 (3.57%) 
Alopecia  1  3/54 (5.56%)  1/56 (1.79%) 
Night sweats  1  3/54 (5.56%)  1/56 (1.79%) 
Pruritus  1  6/54 (11.11%)  6/56 (10.71%) 
Erythema  1  1/54 (1.85%)  2/56 (3.57%) 
Vascular disorders     
Hypertension  1  2/54 (3.70%)  4/56 (7.14%) 
Hypotension  1  0/54 (0.00%)  2/56 (3.57%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Incyte Corporation
Phone: 855 463-3463
Layout table for additonal information
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01632904    
Other Study ID Numbers: 18424-357
First Submitted: June 29, 2012
First Posted: July 3, 2012
Results First Submitted: March 26, 2015
Results First Posted: April 7, 2015
Last Update Posted: November 14, 2017