A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera

Study Overview
=================
Brief Summary
-----------------
The study is designed to evaluate the safety and efficacy of rusfertide in subjects with polycythemia vera (PV) in maintaining hematocrit control and in improving symptoms of PV.

Detailed Description
-----------------
Phase 3 study in approximately 250 subjects previously diagnosed with polycythemia vera (PV) who require phlebotomy on a routine basis. There is a 32-week period during which rusfertide or placebo will be added-on to each subject's ongoing therapy for polycythemia vera which may include phlebotomy only or phlebotomy plus stable doses of either of hydroxyurea, interferon and/or ruxolitinib. All subjects who successfully complete the double blind 32-week portion of the study will receive rusfertide for 124 weeks. Approximately 6 and 12 months after their last dose of rusfertide, subjects will have a post-study contact (e.g. by phone) for safety.

Official Title
-----------------
A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients With Polycythemia Vera

Conditions
-----------------
Polycythemia Vera

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Rusfertide


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled. There are additional inclusion criteria. Male and female subjects aged 18 (or the country specific minimum age of consent >18) years or older. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera. At least 3 phlebotomies due to inadequate hematocrit control in 6 months before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization. CBC values immediately prior to randomization: Hematocrit <45%, WBC 4000/μL to 20,000/μL (inclusive), and Platelets 100,000/μL to 1,000,000/μL (inclusive) Subjects receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen. Subjects treated with phlebotomy alone at randomization must have stopped cytoreductive therapy 2 to 6 months before screening. Main Exclusion Criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled. There are additional exclusion criteria. Clinically meaningful laboratory abnormalities at Screening. Subjects who require phlebotomy at hematocrit levels lower than 45%. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization. Active or chronic bleeding within 2 months prior to randomization. History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer. Subjects with in situ or stage 1 squamous cell carcinoma of the skin, in situ or stage 1 basal cell carcinoma of the skin, or in situ melanoma of the skin identified during screen unless the cancer is adequately treated before randomization. Received Busulfan, Pipobroman or 32Phosphorus within 7 months prior to screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blind (Part 1a): Subjects will be randomized in a blinded fashion to 32 weeks of rusfertide or placebo added-on to each subject's ongoing treatment for polycythemia vera. Open-label (Part 1b + Part 2): Open-label treatment phase during which all subjects who complete Part 1a successfully will receive rusfertide for 124 weeks.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rusfertide<br>Rusfertide (32 Weeks) - Rusfertide (124 Weeks Open-label) | Drug: Rusfertide<br>* Experimental drug<br>|
| Experimental: Placebo<br>Placebo (32 Weeks) - Rusfertide (124 Weeks Open-label) | Drug: Placebo<br>* Placebo<br>Drug: Rusfertide<br>* Experimental drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving a response who receive rusfertide compared to placebo. | Response is defined as absence of phlebotomy eligibility. | Week 20 through Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of mean number of phlebotomies between rusfertide and placebo. |  | Week 0 to Week 32 | 
| Proportion of subjects with HCT values <45% for rusfertide and placebo. |  | Week 0 to Week 32 | 
| Comparison mean change from baseline in total fatigue score based on PROMIS Short Form between rusfertide and placebo. |  | Week 32 | 
| Comparison of mean change from baseline in total MFSAF total score. |  | Week 32 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polycythemia Vera, PV