Trial Outcomes & Findings for Randomized Switch Study From Hydroxyurea to Ruxolitinib for RELIEF of Polycythemia Vera Symptoms: The Relief Study (NCT NCT01632904)

Last Updated: 2017-11-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

110 participants

Primary outcome timeframe

From Baseline to Week 16

Results posted on

2017-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	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. 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 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 Study STARTED	54	56
Overall Study COMPLETED	47	50
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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 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 Study Adverse Event	4	1
Overall Study Physician Decision	0	1
Overall Study Subject decision	3	2
Overall Study Disease Progression	0	1
Overall Study Reason for discontinuation not available	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruxolitinib n=54 Participants 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 n=56 Participants 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 n=110 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 11.68 • n=5 Participants	64.2 years STANDARD_DEVIATION 12.68 • n=7 Participants	63.7 years STANDARD_DEVIATION 12.15 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	22 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	34 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	53 participants n=5 Participants	56 participants n=7 Participants	109 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 16

Population: 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.

Outcome measures

Outcome measures
Measure	Ruxolitinib n=53 Participants 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 n=54 Participants 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.
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	43.4 Percentage of participants	29.6 Percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 16

Population: 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.

The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake.

Outcome measures

Outcome measures
Measure	Ruxolitinib n=53 Participants 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 n=54 Participants 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.
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 Tiredness (n= 50, 53)	40.0 Percentage of participants	26.4 Percentage of participants
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 Itching (n= 48, 50)	54.2 Percentage of participants	32.0 Percentage of participants
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 Muscle aches (n= 47, 49)	38.3 Percentage of participants	30.6 Percentage of participants
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 Night sweats (n= 42, 48)	47.6 Percentage of participants	41.7 Percentage of participants
Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 Sweats while awake (n= 42, 46)	54.8 Percentage of participants	34.8 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: 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.

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

Outcome measures

Outcome measures
Measure	Ruxolitinib n=54 Participants 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 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.
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 Night sweats	29.6 percentage of participants Interval 18.0 to 43.6	—
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 TSS-C	31.5 percentage of participants Interval 19.5 to 45.6	—
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 Tiredness	24.1 percentage of participants Interval 13.5 to 37.6	—
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 Itching	37.0 percentage of participants Interval 24.3 to 51.3	—
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 Muscle aches	20.4 percentage of participants Interval 10.6 to 33.5	—
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 Sweats while awake	37.0 percentage of participants Interval 24.3 to 51.3	—

Adverse Events

Ruxolitinib

Serious events: 5 serious events

Other events: 50 other events

Deaths: 0 deaths

Hydroxyurea

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ruxolitinib n=54 participants at risk 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 n=56 participants at risk 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.
Cardiac disorders Angina unstable	1.9% 1/54 • 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.	0.00% 0/56 • 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.
Vascular disorders Arterial occlusive disease	1.9% 1/54 • 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.	0.00% 0/56 • 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.
Nervous system disorders Cerebral ischemia	1.9% 1/54 • 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.	0.00% 0/56 • 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.
General disorders Chest discomfort	1.9% 1/54 • 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.	0.00% 0/56 • 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.
Investigations Platelet count increased	1.9% 1/54 • 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.	0.00% 0/56 • 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.
Musculoskeletal and connective tissue disorders Spondylolisthesis	1.9% 1/54 • 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.	0.00% 0/56 • 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.
Vascular disorders Deep vein thrombosis	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Renal and urinary disorders Hematuria	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Investigations Hemoglobin decreased	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Renal and urinary disorders Hydronephrosis	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Renal and urinary disorders Renal failure acute	0.00% 0/54 • 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.	1.8% 1/56 • 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.
General disorders Pyrexia	0.00% 0/54 • 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.	1.8% 1/56 • 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.
Infections and infestations Urosepsis	0.00% 0/54 • 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.	1.8% 1/56 • 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.

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 855 463-3463

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER