Efficacy and Safety of P1101 in Polycythemia Vera Patients for Whom the Standard of Treatment is Difficult to Apply

NCT04182100 | Completed Phase 2 Results FDA Drug

• 1 other identifier: A19-201
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 2 single arm study to investigate efficacy and safety of P1101 for adult Japanese patients with PV.

Conditions

Polycythemia Vera (PV)

Keywords

Myeloproliferative Neoplasms

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12

  The primary efficacy endpoint was the phlebotomy-free CHR rate at Months 9 and 12. The phlebotomy-free CHR rate was defined as the proportion of patients who achieved phlebotomy-free CHR at both Months 9 and 12 without phlebotomies during the previous 3 months. A responder in sense of the primary endpoint was a patient who met all of the following criteria at Months 9 and 12: Hematocrit \<45% phlebotomy-free (absence of phlebotomy during the previous 3 months) Platelet count ≤400 × 10\^9/L Leukocyte count ≤10 × 10\^9/L

  12 months

Secondary Outcomes (10)

• Changes in Hct From Baseline

  Baseline, 3 months, 6 months, 9 months and 12 months

• Changes in WBC Count From Baseline

  Baseline, 3 months, 6 months, 9 months and 12 months

• Changes in Plt Count From Baseline

  Baseline, 3 months, 6 months, 9 months and 12 months

• Changes in Spleen Size From Baseline

  Baseline, 3 months, 6 months, 9 months and 12 months

• Time to Requiring no Phlebotomy

  Up to 12 months

Other Outcomes (1)

• Status of Bone Marrow Histological Remission (Optional)

  0 month, 12 months

Study Arms (1)

P1101

EXPERIMENTAL

Conventional treatment based on phlebotomies, low-dose aspirin (acetylsalicylic acid, 75-150 mg/day) plus the subcutaneous administration of pegylated proline-interferon alpha-2b (P1101, ropeginterferon alfa-2b) once every 2 weeks.

Drug: P1101; Drug: Low-dose aspirin; Procedure: Phlebotomy

Interventions

P1101 DRUG

P1101 (ropeginterferon alfa-2b) will be administered subcutaneously every 2 weeks at the starting dose of 100 μg every two weeks (or 50 μg in patients under another cytoreductive therapy). The dose should be gradually increased by 50 μg every two weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelets \<400 x 10\^9/L and leukocytes \<10 x 10\^9/L). The maximum recommended single dose is 500 μg injected every two weeks. The dose will be maintained at the highest level which can be tolerated and delivers best possible disease response.

Also known as: ropeginterferon alfa-2b

P1101

Low-dose aspirin DRUG

Low-dose aspirin (acetylsalicylic acid) (75-150 mg/day) will be given as background therapy during the 12 months of study treatment, unless contraindicated.

Also known as: Low-dose acetylsalicylic acid

P1101

Phlebotomy PROCEDURE

Phlebotomy is performed aiming at a hematocrit \< 45%. When the hematocrit value is 45% or higher, phlebotomy is performed. The volume of phlebotomy per procedure should be 200 to 400 mL while monitoring the circulatory dynamics such as blood pressure and pulse. In the elderly and patients with cardiovascular disorders, a small volume (100-200 mL) should be considered to avoid rapid changes in hemodynamics.

P1101

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥20 years old
• Patients diagnosed with PV according to the WHO 2008 or WHO 2016 criteria
• PV patients for whom the current standard of treatment is difficult to apply. (Patients with a documented history of refractory to HU are excluded.)
• Younger patients (long-term treatment is anticipated)
• Patients who are categorized as low risk, but cytoreduction is recommended due to disease-related signs and symptoms (headache, dizziness, pruritus, night sweats, fatigue, erythromelalgia, vision disorders, scintillating scotoma, early satiety, abdominal distension).
• Patients with HU intolerance
• Total HU treatment duration shorter than 3 years (cumulatively) at screening
• For cytoreduction naïve patients only: PV in need of cytoreductive treatment, defined by fulfilling as one or more of the following criteria at baseline:
• at least one previous well documented major cardiovascular PV-related event in the medical history
• poor tolerance of phlebotomy (defined as a phlebotomy/ procedure-related adverse event causing significant adverse impact on the patient and limiting ability to apply phlebotomy with the intention to keep Hct \<45%)
• frequent need of phlebotomy (more than one phlebotomy within last month prior entering the study)
• platelet counts greater than 1000 x 10\^9/L (for two measurements within the month prior treatment start)
• leukocytosis (WBC\>10 x 10\^9/L for two measurements within the month prior treatment start)
• Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), international normalized ratio (INR) ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 x ULN, aspartate aminotransferase (AST) ≤2.0 x ULN at screening
• Hemoglobin (HGB) ≥10 g/dL at screening

You may not qualify if:

• Patients with symptomatic splenomegaly
• Previous use of IFNα for any indication
• Any contraindications or hypersensitivity to interferon-alfa
• Co-morbidity with severe or serious conditions which may impact patient participation in the study in investigator's opinion
• History of major organ transplantation
• Pregnant or lactating females
• Patients with any other medical conditions, which in the opinion of the Investigator would compromise the results of the study or may impair compliance with the requirements of the protocol
• History or presence of thyroid dysfunction (clinical symptoms of hyper- or hypo-thyroidism) of the autoimmune origin, except late stages cases on the oral thyroid substitution therapy, where potential exacerbation under interferon therapy will not constitute any further harm to the patient
• Documented autoimmune disease (e.g., hepatitis, idiopathic thrombocytopenic purpura \[ITP\], scleroderma, psoriasis, or any autoimmune arthritis)
• Clinically relevant pulmonary infiltrates and pneumonitis at screening, patients with a history of interstitial pulmonary disease
• Active infections with systemic manifestations (e.g., bacterial, fungal, hepatitis B \[HBV\], hepatitis C \[HCV\], or human immunodeficiency virus \[HIV\]) at screening)
• Evidence of severe retinopathy (e.g., cytomegalovirus retinitis \[CMV\], macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) based on the ophthalmological assessment by specialists.
• Uncontrolled depression
• Previous suicide attempts or at any risk of suicide at screening
• Uncontrolled diabetes mellitus (HbA1c level of \> 7% at baseline)

Sponsors & Collaborators

• PharmaEssentia Japan K.K.: lead

Study Sites (8)

Ehime University Hospital

Toon-shi, Ehime, 791-0295, Japan

Location

Mie University Hospital

Tsu, Mie-ken, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

NTT Medical Center Tokyo

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Tokyo Medical University Hospital

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

University of Yamanashi Hospital

Chuo-shi, Yamanashi, 409-3898, Japan

Location

Related Publications (1)

• Qin A, Shimoda K, Suo S, Fu R, Kirito K, Wu D, Liao J, Chen H, Wu L, Su X, Gao Y, Sato T, Li Y, Zhang J, Shen W, Wang W, Zhang L, Jin J, Komatsu N. Population Pharmacokinetics-Pharmacodynamics and Exposure-Response of Ropeginterferon Alfa-2b in Chinese and Japanese Patients With Polycythemia Vera. Pharmacol Res Perspect. 2025 Jun;13(3):e70109. doi: 10.1002/prp2.70109.

  PMID: 40313042 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Myeloproliferative Disorders

Interventions

Aspirin; Phlebotomy

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Hiroaki Kawase
• Organization: PharmaEssentia Japan KK

hiroaki_kawase@pharmaessentia.com

+81-3-6910-5103

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Conventional treatment based on phlebotomies, low-dose aspirin (acetylsalicylic acid, 75-150 mg/day) plus the subcutaneous administration of P1101 (ropeginterferon alfa-2b) once every 2 weeks

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: December 2, 2019
• Study Start: December 20, 2019
• Primary Completion: March 8, 2021
• Study Completion: March 8, 2021
• Last Updated: September 15, 2025
• Results First Posted: September 15, 2025

Record last verified: 2021-12

Locations

JP (8)