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

Phase 2 Single Arm Study of Efficacy and Safety of P1101 for Polycythemia Vera (PV) Patients for Whom the Current Standard of Treatment is Difficult to Apply

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

Study Overview

• Status: Completed
• Conditions: Polycythemia Vera (PV)
• Intervention / Treatment: Drug: P1101; Drug: Low-dose aspirin; Procedure: Phlebotomy

Detailed Description

Eligible patients will be treated with P1101, starting at 100 μg (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.

At week 36 (month 9) and week 52 (month 12), the primary study endpoint, phlebotomy-free CHR, will be analyzed. After completion of the 52-week study duration, provision and administration of P1101, collection of the long-term follow up information (blood parameters, molecular and cytogenetic data, safety parameters and as also the optional bone marrow data) will be continued until the drug becomes commercially available for all study subjects..

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Ehime
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Mie-ken
    • Tsu, Mie-ken, Japan
      • Mie University Hospital
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan, 409-3898
      • University of Yamanashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ≥20 years old
2. Patients diagnosed with PV according to the WHO 2008 or WHO 2016 criteria

3. 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
4. Total HU treatment duration shorter than 3 years (cumulatively) at screening

5. 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)
6. 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
7. Hemoglobin (HGB) ≥10 g/dL at screening
8. Neutrophil count ≥1.5 x 10^9/L at screening
9. Serum creatinine ≤1.5 x ULN at screening
10. Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales (Patients with a borderline of HADS score [score 7 but <10] or patients with necessity [expected benefits are higher than the risks] based on investigators' discretion are required to receive following assessment by psychiatric specialist to confirm the eligibility for IFNα therapy.).
11. 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 28 days following the last dose of the study drug
12. Written informed consent obtained from the patient or the patient's legal representative, and ability for the patient to comply with the requirements of the study

Exclusion Criteria:

1. Patients with symptomatic splenomegaly
2. Previous use of IFNα for any indication
3. Any contraindications or hypersensitivity to interferon-alfa
4. Co-morbidity with severe or serious conditions which may impact patient participation in the study in investigator's opinion
5. History of major organ transplantation
6. Pregnant or lactating females

7. 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

   7-1. 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

   7-2.Documented autoimmune disease (e.g., hepatitis, idiopathic thrombocytopenic purpura [ITP], scleroderma, psoriasis, or any autoimmune arthritis)

   7-3. Clinically relevant pulmonary infiltrates and pneumonitis at screening, patients with a history of interstitial pulmonary disease

   7-4. Active infections with systemic manifestations (e.g., bacterial, fungal, hepatitis B [HBV], hepatitis C [HCV], or human immunodeficiency virus [HIV]) at screening)

   7-5. 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.

   7-6. Uncontrolled depression

   7-7. Previous suicide attempts or at any risk of suicide at screening

8. Uncontrolled diabetes mellitus (HbA1c level of > 7% at baseline)
9. History of any malignancy within for the past 5 years
10. History of alcohol or drug abuse within the last year
11. History or evidence of post polycythemia vera-myelofibrosis (PPV-MF), essential thrombocythemia, or any non-PV MPN
12. Presence of circulating blasts in the peripheral blood within the last 3 months
13. Use of any investigational drug(s), or investigational drug combinations <4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: P1101; 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; 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.; Other Names: ropeginterferon alfa-2b; Drug: Low-dose aspirin; Low-dose aspirin (acetylsalicylic acid) (75-150 mg/day) will be given as background therapy during the 12 months of study treatment, unless contraindicated.; Other Names: Low-dose acetylsalicylic acid; Procedure: Phlebotomy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of P1101	Trough concentration is the measured concentration of a drug at the end of a dosing interval at steady state every 2 weeks. Additionally, serum concentration is measured at hours 0, 24, 48, 96 and 168 after administration at Week 0 and Week 28.	Up to 12 months
Changes in Hct From Baseline	Hct will be recorded every 3 months.	Baseline, 3 months, 6 months, 9 months and 12 months
Changes in WBC Count From Baseline	WBC count will be recorded every 3 months.	Baseline, 3 months, 6 months, 9 months and 12 months
Changes in Plt Count From Baseline	Plt count will be recorded every 3 months.	Baseline, 3 months, 6 months, 9 months and 12 months
Changes in Spleen Size From Baseline	Spleen size will be recorded every 3 months.	Baseline, 3 months, 6 months, 9 months and 12 months
Time to Requiring no Phlebotomy	Time to requiring no phlebotomy is recorded.	Up to 12 months
Time Required to First Response	Time required to first response is defined as time to achieve complete hematological response (CHR) without phlebotomy.	Up to 12 months
Duration of Response Maintenance	Duration of maintained complete hematologic response (CHR) since first achievement of CHR after administration of the study drug will be calculated.	Up to 12 months
Proportion of Subjects Without Thrombotic or Hemorrhagic Events	Thrombotic or hemorrhagic events will be recorded any time during the study. The proportion of subjects without thrombotic or hemorrhagic events is defined as the proportion of subjects experienced no thrombotic and hemorrhagic events during the study period (12 months).	Up to 12 months
Change of JAK2 Mutant Allelic Burden Over Time vs. Baseline	Quantitative JAK2 measurements at screening, Months 3, 6, 9 and 12 (central laboratory) for subjects who signed consent form. Change of JAK2 allelic burden over time will be assessed.	Baseline, 3 months, 6 months, 9 months and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Status of Bone Marrow Histological Remission (Optional)	Status of bone marrow histological remission defined as the disappearance of hypercellularity (age-adjusted), trilineage growth (panmyelosis) and absence of >grade 1 reticulin fibrosis	0 month, 12 months

Collaborators and Investigators

• Sponsor: PharmaEssentia Japan K.K.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): March 8, 2021
• Study Completion (Actual): March 8, 2021

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Polycythemia Vera; Organic Chemicals; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Blood Specimen Collection; Salicylates; Hydroxybenzoates; Aspirin; Phlebotomy
• Other Study ID Numbers: A19-201

Drug and device information, study documents

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