A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of P1101 in Adults With ET

Essential Thrombocythemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05482971
• Other study ID #: EXCEED ET / A22-301
• Status: Recruiting
• Phase: Phase 2
• Start date: September 29, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: PharmaEssentia
• Contact: Jewell Jessup, PhD
• Phone: 1-800-999-2449
• Email: clinicaltrials[@]pharmaessentia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: December 31, 2026
• Est. primary completion date: July 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-a 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

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Ropeginterferon alfa-2b-njft (P1101)
Ropeginterferon alfa-2b-njft (P1101)

Locations

Country	Name	City	State
Canada	University of Calgary Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Paul's Hospital - Providence Health Care	Vancouver	British Columbia
United States	The Winship Cancer Institute Emory University	Atlanta	Georgia
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina (UNC) - Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	University of Virginia - Emily Couric Cancer Center	Charlottesville	Virginia
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Astera HealthCare	East Brunswick	New Jersey
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Marin Cancer Care	Greenbrae	California
United States	East Carolina University	Greenville	North Carolina
United States	John Theurer Cancer Center At Hackensack UMC	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Yale University School of Medicine - Yale Cancer Center	New Haven	Connecticut
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Mercy Health - Paducah Medical Oncology and Hematology	Paducah	Kentucky
United States	Cancer Care Specialists	Reno	Nevada
United States	Washington University School of Medicine - Division of Oncology	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Regional Medical Oncology Center	Wilson	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
PharmaEssentia

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess efficacy of ropeginterferon alfa-2b-njft (P1101) in adult USA/Canadian patients with ET	Efficacy will be based on peripheral blood count remission as defined by hematocrit (HCT) <45%, white blood cell (WBC) count =10 × 109/L, and platelets (PLT) = 400 × 109/L in at least 80% of bi-weekly measurements for a consecutive 32-wek period during the 52-week core study treatment period.	12 months