This is a Phase 3 single arm study to investigate efficacy and safety of P1101's rapid titration for adult Japanese patients with PV.
Eligible patients will be treated with P1101, starting at 250 μg. A starting dose of P1101 is 250 mcg, an intermediate dose is 350 mcg, and a target dose is 500 mcg. As such, subjects will not be exposed to below optimal doses within the first 4 weeks. The maximum recommended single dose is 500 μg injected every two weeks. A primary efficacy endpoint is the rate of phlebotomy-free complete hematologic response (CHR) at Week 24, where CHR is defined as the proportion of patients who have achieved a CHR and have not required phlebotomy in the previous 12 weeks. A responder for the primary endpoint is defined as meeting all of the following criteria at Week 24: Hct (\<45%), WBC (≤10 x 10\^9/L), and PLT (≤400 x 10\^9/L).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
The subjects will be treated with P1101(ropeginterferon alfa-2b), starting at a dose of 250 micrograms. The dose of P1101 will be increased to 350 micrograms 2 weeks later and to 500 micrograms another 2 weeks later, and then P1101 will be administered at a fixed dose of 500 micrograms throughout the treatment period. Although the dose may be reduced to the prior dose for reasons related to the safety or tolerability, the increased dose should be preferably maintained throughout the treatment period. The dose of P1101 will be increased or decreased appropriately depending on the pathological condition in the range up to 500 micrograms.
Low-dose aspirin (acetylsalicylic acid) (75-150 mg/day) will be given as background therapy during the 12 months of study treatment, unless contraindicated.
Mie University Hospital
Mie, Japan
Osaka University Hospital
Osaka, Japan
Kansai Medical University Hospital
Osaka, Japan
Juntendo University Hospital
Tokyo, Japan
Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Week 24
Time frame: 24 weeks
Rate of achieving "phlebotomy-free complete hematologic response (CHR)" (the same criteria as for the primary efficacy endpoint) at both Week 12 and Week 24.
Time frame: Week12, Week24
Time to achieve CHR
Time frame: Up to Week24
Time to reach response maintenance dose (three consecutive doses of the same dose)
Time frame: Up to Week24
Numbers of phlebotomy required and changes in numbers of phlebotomy required from baseline
Time frame: Baseline, up to Week24
Time to first response in peripheral blood count (Hct, WBC, and PLT)
Time frame: Up to Week24
Duration of response in peripheral blood count (Hct, WBC, and PLT)
Time frame: Up to Week24
Improvement of symptoms assessed by MPN-SAF TSS at each visit
Rated on a scale of 0-10 on an 11-point scale, with 0 being no symptoms, 1 being the best, and 10 being the worst.
Time frame: Up to Week24
Proportion of subjects without thrombotic or hemorrhagic events at Weeks 12 and 24
Time frame: Week12, week24
Change from baseline to Week 24 in JAK2 V617F allele burden level
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Phlebotomy is performed aiming at a hematocrit \< 45%. When the hematocrit value is 45% or higher, phlebotomy is performed. The volume of phlebotomy per procedure should be 200 to 400 mL while monitoring the circulatory dynamics such as blood pressure and pulse. In the elderly and patients with cardiovascular disorders, a small volume (100-200 mL) should be considered to avoid rapid changes in hemodynamics.
Tokyo Medical University Hospital
Tokyo, Japan
University of Yamanashi Hospital
Yamanashi, Japan
Time frame: Baseline, week24
Collect and measure Pharmacokinetics (PK) at trough
Time frame: Day1, Week2, Week4, Week6, Week8, Week10, Week12, Week14, Week16, Week18, Week20, Week22, Week24