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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

Phase III Study in Primary Myelofibrosis (PMF)

Sato Toshiaki

PharmaEssentia Japan K.K.

1-3-13 Motoakasaka, Minato-ku, Tokyo, Japan

toshiaki_sato@pharmaessentia.com

Sato Mai

PharmaEssentia Japan K.K.

1-3-13 Motoakasaka, Minato-ku, Tokyo, 107-0051, Japan

+81-3-6910-5103

mai_sato@pharmaessentia.com

Not Recruiting

Dec. 01, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

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 x upper limit of normal (ULN), international normalized ratio (INR) =<1.5 x ULN, albumin >3.5 g/dL, alanine aminotransferase (ALT) =<2.0 x ULN, and aspartate aminotransferase (AST) =<2.0 x ULN;
4.Hgb >=10.0 g/dL at screening;
5.Neutrophil count >=1.0 x 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.

1.Any known contraindications to interferon alfa or hypersensitivity to interferon alfa
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-alfa) 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.

Both

Myelofibrosis

Eligible patients will be enrolled and randomized in a 2:1 ratio to receive the treatment of ropeginterferon alfa-2b or placebo control in the study. Patients will receive ropeginterferon alfa-2b or placebo biweekly.

Myeloproliferative nemoplasms

Clinically relevant complete hematologic response (CrCHR) at 56 weeks and Symptom endpoint at 56 or possibly 80 weeks
The CrCHR is defined as:
- Platelet count =<400 x 10^9/L, and
- White blood cells (WBC) =<10 x 10^9/L, and
- Peripheral blood: Hemoglobin (Hgb) >10.0 g/dL, and
- Absence of major thrombotic events, and
- No progression to secondary acute myeloid leukemia (AML).
The symptom endpoint is defined as:
- No progression on clinical symptoms based on the MFSAF Total Symptom Score (TSS) v4.0; no progression on clinical symptoms defined as:
- If baseline TSS score =<10, TSS score stays =<10; or
- If baseline TSS score >10, no increase >50% in TSS score.

Incidence of adverse events (AEs) and serious adverse events (SAEs)

No

none