Keywords:Polycythemia Vera , Myeloproliferative Neoplasm , Hydrea , Jak2 inhibitor , Fatigue , Splenomegaly , Pruritis , Jakafi , Hematocrit , Phlebotomy
PRIMARY: To compare the efficacy of ruxolitinib and HU for reducing the cluster of symptoms defined by tiredness, itching, muscle aches, night sweats, and sweats while awake in subjects with PV.
SECONDARY: To compare the efficacy of ruxolitinib and HU for reducing the following individual symptoms:
− Muscle aches
− Night sweats
− Sweats while awake
To evaluate the durability of symptomatic improvement in subjects experiencing relief from the cluster of symptoms that includes tiredness, itching, muscle aches, night sweats, and sweats while awake, and for each of these symptoms individually.
To evaluate the safety of ruxolitinib and HU.
1. Subjects must be able to comprehend and be willing to sign an informed consent form (ICF).
2. Subjects must be 18 years of age or older.
3. Subjects must have confirmed diagnosis of PV according to the revised WHO criteria.
4. 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 have been on the same dose for the last 4 weeks.
5. Subjects must have completed the modified MPN-SAF screening symptom form and have a screening TSS of ≥ 8 for the symptom cluster C (TSS-C): tiredness, itching, muscle aches, night sweats, and sweats while awake.
6. Subjects should meet at least 1 of the following criteria with respect to phlebotomy and splenomegaly:
a. No more than 1 phlebotomy within the 6 months before screening OR
b. No palpable splenomegaly.
7. Subjects must have a HCT that can be controlled within 35% to 48% (inclusive) before randomization. (A phlebotomy may be performed during the screening period to achieve this target range.)
8. Subjects must have recovered from all side effects associated with phlebotomy, and at least 1 week must have elapsed between the phlebotomy and the beginning of the baseline phase.
9. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.
10. Subjects must be willing to and capable of complying with the requirements of the study.
11. Females must have a negative serum pregnancy test at screening and be one of the following:
a. Postmenopausal for at least 1 year with documented follicle-stimulating hormone (FSH) > 30 IU/L; or
b. Surgically sterile for at least 3 months; or
c. Of child-bearing potential and agree to take appropriate precautions to avoid pregnancy from screening through follow-up. (Note: Permitted methods that are highly effective in preventing pregnancy should be communicated to subjects and their understanding confirmed).
1. Pregnant or breastfeeding women, or subjects (male or female) unwilling to take appropriate measures to avoid pregnancy.
2. Subjects with inadequate liver or renal function at screening as demonstrated by any of the following:
c. Encephalopathy ≥ Grade 2 as per Child-Pugh System
d. Hepatocellular disease
e. Total bilirubin > 2 . the upper limit of normal (ULN; unless direct bilirubin is < 2 . ULN)
f. Alanine aminotransferase (ALT) > 2.5 . ULN
g. Modification of Diet in Renal Disease estimated glomerular filtration rate < 30 mL/min/1.73 m2, or requiring dialysis
3. Subjects with PLT count < 100 . 109/L or an ANC of < 1 . 109/L
4. Subjects with impairment of GI function or active GI disease that may significantly alter absorption of ruxolitinib (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, and small bowel obstruction).
5. Subjects with clinically significant bacterial, fungal, parasitic, mycobacterial, or viral infection that requires therapy:
a. Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
b. Subjects with known active hepatitis A, B, or C at screening or with known HIV positivity.
6. Subjects with peripheral blood blast count of > 0% at screening.
7. Subjects with an active malignancy over the previous 2 years except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or completely resected papillary thyroid and follicular thyroid cancers.
8. Subjects with clinically significant cardiac disease (Class III or IV) as defined by the New York Heart Association.
9. Subjects receiving therapy for PV other than HU or aspirin within 12 weeks before screening or having a history of 32P therapy.
10. Subjects being treated concurrently with a potent systemic inhibitor of CYP3A4 at the time of screening.
11. Subjects being treated concurrently with any prohibited medications
12. Subjects who have previously received treatment with a JAK inhibitor.
13. Subjects being treated concurrently with any investigational agent or prior participation in an investigational study within 30 days before the first dose of study drug or within 5 half-lives of the investigational product, whichever is longer.
14. Subjects who are unable to comprehend or are unwilling to sign an ICF.
15. Subjects with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
16. Subjects with an uncontrolled intercurrent illness or any concurrent condition that, in the investigator’s opinion, would jeopardize the safety of the subject or compliance with the protocol.