P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk

A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase III Study to Assess Efficacy and Safety of Ropeginterferon Alfa-2b (P1101) in Adult Patients With Pre-fibrotic/Early Primary Myelofibrosis (PMF) or Overt PMF at Low or Intermediate-1 Risk According to DIPSS Plus

This is a phase 3 double-blind clinical trial arm to test Ropeginterferon alfa-2b (P1101) in adult patients with Primary Myelofibrosis (PMF) at early stage or low to medium risk.

Participants will receive the study drug/placebo bi-weekly and have an assessment visit every 4 weeks. The ratio of study drug to placebo group is 2:1.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Myelofibrosis; Myeloproliferative Neoplasm
• Intervention / Treatment: Biological: Ropeginterferon alfa-2b; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ting-Fang Wang; Phone Number: +886-2-26557688; Email: tingfang_wang@pharmaessentia.com
• Study Contact Backup: Name: Aypiin Shen; Phone Number: +886-2-26557688 Ext. 7896; Email: aypiin_shen@pharmaessentia.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged ≥18 years at the time of signing the informed consent form;
2. Patients with pre-fibrotic/early PMF (Pre-PMF) or overt primary myelofibrosis at low to intermediate-1 risk according to DIPSS plus, diagnosed according to WHO 2016 or 2022 classification;
3. 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. Hgb ≥10.0 g/dL at screening;
5. Neutrophil count ≥1.0 × 10^9/L at screening;
6. Creatinine clearance rate ≥30 mL/min at screening (according to the Cockcroft-Gault formula);
7. 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 known contraindications to interferon α or hypersensitivity to interferon α;
2. Patients with prior interferon therapy having poor tolerability or lack of efficacy to the previous interferon therapy per investigator's judgement;
3. Patients with an ongoing cytoreduction (e.g., HU or IFN-α) at the time of screening if, in the Investigator's opinion, randomizing them into the placebo arm will lead to immediate rebound increase of peripheral blood counts and thus may jeopardize their health status;
4. With severe or serious diseases that, in the Investigator's opinion, may affect the patient's participation in this study;
5. History of major organ transplantation;
6. Pregnant or breastfeeding women;
7. Patients with any other diseases that will affect the study results or may weaken the compliance to protocol per the Investigator's judgment;
8. 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.
9. Eligible for JAK inhibitor therapy at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Ropeginterferon alfa-2b is administrated subcutaneously (SC) every two weeks (± 3 days) until 56 weeks.	Biological: Ropeginterferon alfa-2b; Pre-filled Syringe. Dosage: up to 500mcg; Other Names: P1101
Placebo Comparator: Control group; Placebo is administrated subcutaneously (SC) every two weeks (± 3 days) until 56 weeks.	Other: Placebo; Placebo is a look-alike substance with the intervention (Ropeginterferon alfa-2b) that contains no active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant Complete Hematologic Response (CrCHR): Platelet count, and	≤400 × 10^9/L	56 weeks
CrCHR: White Blood Cells (WBC) count, and	<10 × 10^9/L	56 weeks
CrCHR: Peripheral blood: Hemoglobin (Hgb), and	>10.0 g/dL	56 weeks
CrCHR: Absence of thrombotic events, and	Absence of major thrombotic events during the observation time frame	56 weeks
CrCHR: No progression to AML, or	No progression to secondary acute myeloid leukemia (AML)	56 weeks
Symptom endpoint	No progression on clinical symptoms based on the MFSAF Total Symptom Score (TSS) v4.0	56 weeks

Collaborators and Investigators

• Sponsor: PharmaEssentia
• Investigators: Study Director: Toshiaki Sato, MD/PhD, PharmaEssentia JP

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Estimated): June 21, 2024

Study Record Updates

• Last Update Posted (Estimated): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: MPN; P1101; PMF; Primary Myelofibrosis; Myeloproliferative neoplasms; Ropeginterferon; PharmaEssentia; Pre-fibrotic; Low or Intermediate-1 Risk
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Primary Myelofibrosis; Myeloproliferative Disorders
• Other Study ID Numbers: A23-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No