Polycythemia Vera
Conditions
Keywords
polycythemia vera
Brief summary
This is a Phase 2 study with an open-label dose escalation phase followed by a blinded withdrawal phase and an open label extension. The study is designed to monitor the PTG-300 safety profile and to obtain preliminary evidence of efficacy of PTG-300 for the treatment of phlebotomy-requiring polycythemia vera.
Detailed description
Phase 2 study in approximately sixty subjects previously diagnosed with Polycythemia Vera who require phlebotomy on a routine basis. There is a 28 week dose finding phase to identify a dose that maintains hematocrit \<45%. Subjects who successfully complete the dose finding phase will be entered into a 12 week randomized withdrawal phase to confirm the response. Subsequently patients will enter into an up to 3 year open label extension to investigate long term safety.
Interventions
DRUGPTG-300
Active
DRUGPlacebo
Placebo
Sponsors
Protagonist Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Part 1 open label, Part 2 blinded, Part 3 open label
Intervention model description
Part 1: 28 week open-label dose escalation phase in which each subject's dose of PTG-300 is titrated to achieve a hematocrit \<45%. Part 2: 12-week blinded randomized withdrawal phase. Subjects are randomized 1:1 to continue PTG-300 or to receive placebo. Part 3: Up to 3 year open label extension.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled. 1. Male and female subjects aged 18 years or older. 2. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera. 3. Records of all phlebotomies performed for at least 28 weeks (preferably up to 52 weeks) before dosing are available. 4. Subjects who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before screening and have recovered from any adverse events due to cytoreductive therapy. 5. Subjects receiving cytoreductive therapy with hydroxyurea, interferon, or ruxolitinib must have received cytoreductive therapy for at least 24 weeks and be on a stable dose or have a decreasing dose (Medical Monitor approval required) for at least 8 weeks before dosing and with no planned change in dose. Main
Exclusion criteria
Subjects must meet NONE of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of responders during the blinded randomized withdrawal period (Week 29 to Week 41). | 12 weeks | A subject will be considered a responder during the blinded randomized withdrawal phase if hematocrit control is maintained without phlebotomy eligibility. Phlebotomy eligibility is defined as any one of the following criteria being met: * hematocrit ≥45% that was ≥3% higher than Week 29 pre-randomization hematocrit value, or * hematocrit \>48%, or * an increase of ≥5% in hematocrit compared to Week 29 pre-randomization hematocrit value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in rate of phlebotomy events between Week 17 through Week 29 (inclusive; 12 weeks) compared to each subject's historical rate. | 12 weeks | — |
| Change in rate of phlebotomy events between Week 1 through Week 29 (inclusive; 28 weeks) compared to each subject's historical rate. | 28 weeks | — |
| Proportion of subjects achieving a response at Week 29, with response defined as having achieved the absence of phlebotomy eligibility during the efficacy evaluation phase beginning at Week 17 and continuing to Week 29. | 12 Weeks | Phlebotomy eligibility in Part 1 is defined as a hematocrit ≥45% that was ≥3% higher than baseline level (defined as Part 1 pre-dose Day 1) or a hematocrit \>48%. |
| Proportion of subjects with reduction in the rate of phlebotomy events beginning at the Week 17 visit and continuing to Week 29 (12 weeks) compared to each subject's historical rate. | 12 Weeks | Time to phlebotomy eligibility from Week 29 to Week 41/End of Part 2. |
Countries
India, United States
Outcome results
None listed