A phase 3 clinical trial is evaluating the efficacy and safety of Ropeginterferon alfa-2b (Ropeg) in patients with early/lower-risk primary myelofibrosis (PMF). This randomized, double-blind, placebo-controlled, multi-center study aims to address the unmet needs in treating early-stage PMF, where current options are limited. The trial is enrolling patients with pre-fibrotic or low to intermediate-1 risk PMF based on the Dynamic International Prognostic Scoring System-plus (DIPSS-plus).
Study Design and Objectives
The study randomizes eligible patients in a 2:1 ratio to receive either Ropeg or a placebo. The treatment period lasts 56 weeks, followed by a 4-week safety follow-up. Patients completing the core study can enter an extended 56-week open-label treatment phase. Ropeg is administered subcutaneously every two weeks, with dose adjustments based on tolerability. The co-primary endpoints are clinically relevant complete hematologic response (CrCHR) and improvement in myelofibrosis-associated symptoms.
Eligibility Criteria
Key inclusion criteria include patients aged 18 years or older with a diagnosis of pre-fibrotic or overt PMF at low/intermediate-1 risk according to DIPSS-plus, a white blood cell count greater than 10 x 10^9/L or platelet count of 450 x 10^9/L or higher, and a hemoglobin level of 10 g/dL or greater. Exclusion criteria include prior intolerance to interferon alfa, eligibility for JAK inhibitor therapy, and certain autoimmune or severe systemic diseases.
Dosing and Assessments
The starting dose of Ropeg is 250 μg, with potential titration to 350 μg and then 500 μg every two weeks. Doses can be adjusted based on tolerability. Assessments include regular clinical and hematologic tests, bone marrow biopsies, and safety evaluations. The study also monitors molecular responses in driver and non-driver mutations.
Endpoints and Sample Size
The co-primary endpoints are CrCHR, defined by specific hematologic criteria and absence of thrombotic events or progression to acute myeloid leukemia, and symptom improvement based on the Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS). Secondary endpoints include changes in mutant allele frequencies, spleen size, time to disease progression, progression-free survival, event-free survival, and bone marrow response. The study plans to enroll approximately 150 patients to achieve sufficient statistical power.
Rationale for Ropeginterferon Alfa-2b
Ropeginterferon alfa-2b is a novel PEGylated interferon alfa with a favorable pharmacokinetic profile. It is already approved for treating polycythemia vera (PV) and is under development for other indications. Unlike some other treatments, Ropeg has not been shown to cause clinically significant anemia in PV patients. The trial aims to determine if Ropeg can provide clinical efficacy and tolerability in early/lower-risk PMF, where there is a need for disease-modifying agents.
