Clinical trial NCT05481151: A Study to Assess Efficacy, Safety, and Tolerability of P1101 in Adult Patients With PV
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Polycythemia Vera
Keywords: Polycythemia Vera
Essential Thrombocythemia
P1101
Ropeginterferonalfa-2b-njft
Polycythemia
Vera
PharmaEssentia
Besremi
Ropeg
Lead sponsor: PharmaEssentia
Sponsor class: INDUSTRY
First posted: 2022-08-01
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects aged ≥18 years at the time of signing the informed consent form
2. Subjects diagnosed with PV according to the 2008 or 2016 World Health Organization (WHO) criteria
3. 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
4. Hemoglobin (HGB) ≥10 g/dL for females, and HGB ≥11 g/dL for males at screening
5. Neutrophil count ≥1.5 × 10\^9/L at screening
6. Creatinine clearance rate ≥40 mL/min at screening (according to the Cockcroft-Gault formula)
7. 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
8. Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study

Exclusion Criteria:

1. Any contraindications to interferon alfa or hypersensitivity to interferon alfa
2. Subjects who stopped prior to interferon alfa therapy due to low efficacy or poor tolerability
3. Subjects with severe or serious diseases that the Investigator determines may affect the subject's participation in this study
4. History of major organ transplantation
5. Pregnant or breastfeeding women
6. 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:

   1. Prior or current autoimmune thyroid disease (clinical symptoms of hyper- or hypo-thyroidism), except subjects with controlled thyroid replacement therapy, could be enrolled
   2. Other documented autoimmune diseases (such as hepatitis, immune thrombocytopenia \[ITP\], scleroderma, psoriasis, or any autoimmune arthritis)
   3. Clinically significant pulmonary infiltration, infectious pneumonia, and non-infectious pneumonia, or a past history of interstitial pneumonia at screening
   4. 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)
   5. Evidence of severe retinopathy (e.g., cytomegalovirus \[CMV\]-induced retinitis, macular degeneration) or clinically significant eye diseases (due to diabetes or hypertension)
   6. History or presence of clinically relevant depression per Investigator's judgment
   7. Previously had suicidal attempts or has any risk for suicidal tendency at screening
   8. Poorly controlled diabetes defined as HbA1c \>8.0% for at least 1 year
   9. Active thromboembolic complications caused by PV and abdominal hemorrhage in the active phase
   10. 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)
   11. History of alcohol or drug abuse in the past year
   12. History or evidence of post-polycythemia vera-myelofibrosis (PPV-MF), essential thrombocythemia, or any non-PV MPN
   13. Presence of blast cells in the peripheral blood in the past 12 weeks
7. 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
8. Any subject requiring a legally authorized representative

Primary outcomes:
measure: 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.
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Baptist MD Anderson
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Paducah
country: United States
facility: Mercy Health
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland PA (Center for Cancer & Blood Disorders)
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: East Brunswick
country: United States
facility: Astera HealthCare
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: High Point
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia - Emily Couric Cancer Center
state: Virginia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Center - Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: PharmaEssentia Corporation
name: Ole Zagrijtschuk, MD, PhD
role: STUDY_DIRECTOR
References: