Polycythemia Vera
Conditions
Keywords
Polycythemia Vera, PV
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.
Interventions
DRUGRuxolitinib
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.
DRUGHydroxyurea (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.
DRUGHU-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.
DRUGRuxolitinib-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.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Belgium, Germany, Ireland, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 54 |
| 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. | 56 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Disease Progression | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Reason for discontinuation not available | 0 | 1 |
| Overall Study | Subject decision | 3 | 2 |
Baseline characteristics
| Characteristic | Ruxolitinib | Hydroxyurea | Total |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 11.68 | 64.2 years STANDARD_DEVIATION 12.68 | 63.7 years STANDARD_DEVIATION 12.15 |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White or Caucasian | 53 participants | 56 participants | 109 participants |
| Sex: Female, Male Female | 30 Participants | 22 Participants | 52 Participants |
| Sex: Female, Male Male | 24 Participants | 34 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 54 | 45 / 56 |
| serious Total, serious adverse events | 5 / 54 | 4 / 56 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | 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 |
| Hydroxyurea | 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 | 29.6 Percentage of participants |
p-value: 0.13995% CI: [0.82, 4.04]Chi-squared
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Hydroxyurea | 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) | 34.8 Percentage of participants |
| Hydroxyurea | Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | Tiredness (n= 50, 53) | 26.4 Percentage of participants |
| Hydroxyurea | Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | Muscle aches (n= 47, 49) | 30.6 Percentage of participants |
| Hydroxyurea | Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | Night sweats (n= 42, 48) | 41.7 Percentage of participants |
| Hydroxyurea | Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | Itching (n= 48, 50) | 32.0 Percentage of participants |
Secondary
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
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |
| Ruxolitinib | 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 |