Clinical trial NCT05482971: A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of P1101 in Adults With ET
Official title: A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Ropeginterferon Alfa-2b-njft (P1101) in Adult Patients With Essential Thrombocythemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Essential Thrombocythemia
Keywords: MPN
Myeloproliferative
Neoplasms
Myeloproliferative Neoplasms
Essential
Thrombocythemia
Besremi
Ropeginterferon Alfa-2b-njft
P1101
Essential Thrombocythemia
Lead sponsor: PharmaEssentia
Sponsor class: INDUSTRY
First posted: 2022-08-01
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Ropeginterferon alfa-2b-njft (P1101) in Adult Patients with Essential Thrombocythemia

Detailed description: PharmaEssentia is developing a pegylated (PEG) IFN-α product, P1101, for the treatment of Essential Thrombocythemia (ET) as lack of disease modifying therapies in essential ET constitutes a serious issue in modern hematology.

Ropeginterferon alfa-2b-njft (P1101) may represent an effective, well-tolerated treatment with the ability to provide a deeper response and superior control of important blood parameters with the potential to alter the course of the disease and prevent progression to post-ET myelofibrosis (MF) and/or secondary acute myeloid leukemia (sAML). Ropeginterferon alfa-2b-njft (P1101) is currently being evaluated in comparison to ANA in the ongoing global Phase 3 clinical study, SURPASS ET.

Enrolled patients will receive P1101 over 13 months followed by an extension period.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects ≥18 years old.
2. Subjects diagnosed with ET according to the World Health Organization (WHO) 2016 criteria.
3. Subjects that are cytoreductive treatment-naïve, or pre-exposed to HU and/or ANA, as specified below (according to Investigator's judgment and documented in the patient's medical record):

   a. Cytoreductive-naïve patients must be in need of cytoreductive treatment, defined as having at least one of the following:

   i. Progressive leukocytosis and/or thrombocytosis

   ii. Disease-related symptoms (i.e., pruritus, night sweats, fatigue)

   iii. Vasomotor/microvascular disturbances, not responsive to aspirin (including headache, chest pain or erythromelalgia, etc.)

   iv. High-risk (history of thrombosis at any age; or age \>60 years with JAK2 mutation)

   b. Patients previously exposed to HU will be classified as either:

   i. Documented formal HU resistance or intolerance

   ii. HU stopped without documented formal resistance/intolerance due to insufficient blood count control or toxicity. The last HU dose must be \>7 days prior the first dose of P1101.
4. Adequate hepatic function defined as bilirubin ≤1.5 × upper limit normal (ULN), prothrombin time (PT) (international normalized ratio, \[INR\]) ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at screening.
5. Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation).
6. 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.
7. Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study.
8. Platelet count \>450 × 109/L at screening
9. Both ANA-naïve and ANA-pretreated subjects are eligible for the study, regardless of the reason to terminate ANA use

Exclusion Criteria:

1. Any subject requiring a legally authorized representative
2. Subjects who stopped prior interferon alfa therapy due to low efficacy or poor tolerability
3. Any contraindications or hypersensitivity to IFN-α and/or its excipients
4. Co-morbidity with severe or serious condition that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol, including significant cardiac disease (including New York Heart Association Class III-IV congestive heart failure and clinically significant arrhythmias) and pulmonary hypertension
5. History of major organ transplantation
6. Pregnant or lactating females
7. Subjects with any significant medical conditions that, in the opinion of the Investigator, would compromise the results of the study or may impair compliance with the requirements of the protocol, including but not limited to:

   1. Documented autoimmune disease at screening or in the history (e.g., thyroid dysfunction, hepatitis, idiopathic thrombocytopenic purpura, scleroderma, psoriasis, or any arthritis of autoimmune origin)
   2. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol
   3. Infections with systemic manifestations (e.g., bacterial, fungal, or human immunodeficiency virus \[HIV\], except hepatitis B \[HBV\] and/or hepatitis C \[HCV\],at screening)
   4. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis \[CMV\], macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension)
   5. History or presence of clinically relevant depression
   6. Previous suicide attempts or at any risk of suicide at screening, in the judgment of the Investigator
   7. History or presence of clinically significant neurologic diseases
   8. History of any malignancy within 5 years (except adequately treated nonmelanoma 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)
   9. History of alcohol or drug abuse within the last year
   10. History or evidence of any other MPN
8. Use of any investigational drug \<4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent
9. Presence of more than one driver mutation (e.g., V617F JAK2 and CALR, CALR and MPL, V617F JAK2 and MPL)
10. Prior use of JAK inhibitors

Primary outcomes:
measure: To assess efficacy of ropeginterferon alfa-2b-njft (P1101) in adult USA/Canadian patients with ET
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: The Winship Cancer Institute Emory University
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Paducah
country: United States
facility: Mercy Health - Paducah Medical Oncology and Hematology
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Division of Oncology
state: Missouri
city: Reno
country: United States
facility: Cancer Care Specialists
state: Nevada
city: East Brunswick
country: United States
facility: Astera HealthCare
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center At Hackensack UMC
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina (UNC) - Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Wilson
country: United States
facility: Regional Medical Oncology 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 Cancer Center
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: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital - Providence Health Care
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: PharmaEssentia Corporation
name: Oleh Zagrijtschuk, MD, PhD
role: STUDY_DIRECTOR
References: