A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV

Study Overview
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Brief Summary
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A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients with PV

Detailed Description
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Polycythemia vera (PV) is the most common type of chronic myeloproliferative neoplasm (MPN), with an annual reported incidence of up to 2.6/100,000. This is a long-term debilitating and life-threatening disease because it is associated with the risk of thrombosis, bleeding, and progression to myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) Ropeginterferon alfa-2b-njft (P1101), which gained US marketing authorization in November 2021, is the only interferon alfa approved for the treatment of PV. This study aims to evaluate the efficacy, tolerability, and safety of ropeginterferon alfa-2b-njft (P1101) in US and Canadian PV patients, utilizing an optimized dosing regimen.

Official Title
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A Phase IIIb, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-njft (P1101) in Adult Patients With Polycythemia Vera (PV)

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: P1101 (Ropeginterferon alfa-2b-njft)
* Drug: Ropeginterferon alfa-2b-njft (P1101)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged ≥18 years at the time of signing the informed consent form Subjects diagnosed with PV according to the 2008 or 2016 World Health Organization (WHO) criteria Subjects with good liver function at screening, which is defined as total bilirubin ≤1.5 × upper limit of normal (ULN), international normalized ratio (INR) ≤1.5 × ULN, albumin >3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 × ULN, and aspartate aminotransferase (AST) ≤2.0 × ULN Hemoglobin (HGB) ≥10 g/dL for females, and HGB ≥11 g/dL for males at screening Neutrophil count ≥1.5 × 10^9/L at screening Creatinine clearance rate ≥40 mL/min at screening (according to the Cockcroft-Gault formula) Males and females of childbearing potential, as well as all women <2 years after the onset of menopause, must agree to use an acceptable form of birth control until 60 days following the last dose of the study drug, and females must agree to not breastfeed during the study Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study Exclusion Criteria: Any contraindications to interferon alfa or hypersensitivity to interferon alfa Subjects who stopped prior to interferon alfa therapy due to low efficacy or poor tolerability Subjects with severe or serious diseases that the Investigator determines may affect the subject's participation in this study History of major organ transplantation Pregnant or breastfeeding women Subjects with any other diseases that the Investigator determines will affect the study results or may weaken the compliance to protocol, including but not limited to: Prior or current autoimmune thyroid disease (clinical symptoms of hyper- or hypo-thyroidism), except subjects with controlled thyroid replacement therapy, could be enrolled Other documented autoimmune diseases (such as hepatitis, immune thrombocytopenia [ITP], scleroderma, psoriasis, or any autoimmune arthritis) Clinically significant pulmonary infiltration, infectious pneumonia, and non-infectious pneumonia, or a past history of interstitial pneumonia at screening Active infection with systemic manifestations (e.g., presence of bacteria, fungi, and/or human immunodeficiency virus [HIV] at screening, excluding hepatitis B [HBV] and/or hepatitis C [HCV] at screening) Evidence of severe retinopathy (e.g., cytomegalovirus [CMV]-induced retinitis, macular degeneration) or clinically significant eye diseases (due to diabetes or hypertension) History or presence of clinically relevant depression per Investigator's judgment Previously had suicidal attempts or has any risk for suicidal tendency at screening Poorly controlled diabetes defined as HbA1c >8.0% for at least 1 year Active thromboembolic complications caused by PV and abdominal hemorrhage in the active phase History of any malignancy within 5 years (except adequately treated non-melanoma skin cancer, prostate cancer status post resection with an undetectable prostate-specific antigen (PSA), curative treated in-situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage 1 Grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥2 years prior to study) History of alcohol or drug abuse in the past year History or evidence of post-polycythemia vera-myelofibrosis (PPV-MF), essential thrombocythemia, or any non-PV MPN Presence of blast cells in the peripheral blood in the past 12 weeks Use any investigational drug <4 weeks prior to the first dose of study drug, or not recovered from effects of prior administration of any investigational drug Any subject requiring a legally authorized representative

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P1101 250-350-500mcg<br>Pre-filled Syringe, Q2W starting at 250-350-500, SC injection | Drug: P1101 (Ropeginterferon alfa-2b-njft)<br>* Ropeginterferon alfa-2b-njft<br>|
| Active Comparator: Ropeginterferon alfa-2b-njft<br>Pre-filled Syringe, Q2W starting at 100 up to 500 (50mcg increases), SC injection | Drug: Ropeginterferon alfa-2b-njft (P1101)<br>* Ropeginterferon alfa-2b-njft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare efficacy, safety, and tolerability of P1101 utilizing 250-350-500 mcg compared to the current labeled dosing through assessing the proportion of subjects that are in a complete hematologic response at Week 24. | CHR is defined as hematocrit (HCT) <45%, white blood cell (WBC) count <10 × 10^9/L, platelets (PLT) ≤400 × 10^9/L in the absence of phlebotomy in the previous 12 weeks. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycythemia Vera, Essential Thrombocythemia, P1101, Ropeginterferonalfa-2b-njft, Polycythemia, Vera, PharmaEssentia, Besremi, Ropeg