A Study to Evaluate P1101 in Japanese PV Patients

A Phase III b, Single-arm, Multicenter, Optimal Dose Finding Study to Assess the Efficacy and Safety of P1101 in Japanese Patients With Polycythemia Vera (PV).

This is a Phase 3 single arm study to investigate efficacy and safety of P1101's rapid titration for adult Japanese patients with PV.

Study Overview

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

Detailed Description

Eligible patients will be treated with P1101, starting at 250 μg. A starting dose of P1101 is 250 mcg, an intermediate dose is 350 mcg, and a target dose is 500 mcg. As such, subjects will not be exposed to below optimal doses within the first 4 weeks. The maximum recommended single dose is 500 μg injected every two weeks.

A primary efficacy endpoint is the rate of phlebotomy-free complete hematologic response (CHR) at Week 24, where CHR is defined as the proportion of patients who have achieved a CHR and have not required phlebotomy in the previous 12 weeks. A responder for the primary endpoint is defined as meeting all of the following criteria at Week 24: Hct (<45%), WBC (≤10 x 10^9/L), and PLT (≤400 x 10^9/L).

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Mie, Japan, 514-8507
    • Mie University Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Yamanashi, Japan, 409-3898
    • University of Yamanashi Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female patients ≥18 years old at the time of informed consent to participate in the study
2. Patients diagnosed with PV according to the WHO 2008 or 2016 criteria
3. Patients with PV who have the inadequate response to an existing therapy or whom the existing therapy is inappropriate to apply (see Appendix 6)
4. Patients with adequate hepatic function at screening defined as total bilirubin ≤1.5 x upper limit of normal (ULN), international normalized ratio (INR) of prothrombin time (PT) ≤1.5 x ULN, albumin >3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 x ULN, and aspartate aminotransferase (AST) ≤2.0 x ULN.
5. Patients with hemoglobin (HGB) ≥10 g/dL in female and ≥11 g/dL in male at screening
6. Patients with a neutrophil count ≥1.5 x 10^9/L at screening
7. Patients with serum creatinine ≤1.5 x ULN at screening
8. 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 14 days following the last dose of the study drug. Also, women must agree not to breastfeed during the study (see Appendix 4 for details)
9. Written informed consent has been obtained from the patient or the patient's legally authorized representative, and the patient is capable of complying with the study requirements.

Exclusion Criteria:

1. Patients with contraindications to or hypersensitivity to IFN-α
2. Patients with previous use of IFN-α, or previous treatment with ruxolitinib
3. Patients with comorbidity with severe or serious condition that, in the opinion of the Investigator, may impact the patient's participation in the study
4. Patients with a history of major organ transplantation
5. Pregnant or lactating females

6. Patients with any other medical condition that, in the opinion of the Investigator, might impair the outcome of the study or compliance with the requirements of the protocol. These diseases include, but are not limited to, the following:

   6.1 Patients with a history or presence of autoimmune thyroid dysfunction (clinical symptoms of hyper- or hypo-thyroidism), 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 6.2 Patients with any documented history of autoimmune disease (for example, hepatitis, idiopathic thrombocytopenic purpura [ITP], scleroderma, psoriasis, or autoimmune arthritis) 6.3 Patients with clinically relevant pulmonary infiltrates, infectious pneumonia or noninfectious pneumonia at screening, or a history of interstitial pulmonary disease.

   6.4 Patients with active infection with systemic symptoms (for example, bacterial, fungal, hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection at screening).

   6.5 Patients with any evidence of severe retinal disease (e.g., cytomegalovirus [CMV] retinitis, macular degeneration) or clinically relevant ophthalmologic disease (due to diabetes mellitus or hypertension) based on the ophthalmological assessment by specialists.

   6.6 Patients with uncontrolled depression in the opinion of the Investigator 6.7 Patients with a history of suicide attempts or at risk for suicide at screening 6.8 Patients with uncontrolled diabetes mellitus (baseline HbA1c >7%) 6.9 Patients with active thromboembolism or active abdominal bleeding due to PV 6.10 Patients with a history of malignancy within the last 5 years [excluding adequately treated non-melanoma skin cancers, post-prostatectomy prostate-specific antigen (PSA) failure, healed cervical intraepithelial neoplasia and ductal carcinoma in situ (DCIS), stage 1 endometrial carcinoma, or solid tumors (without myelopathy), including other lymphomas that have not had evidence of disease for at least 2 years after treatment].

   6.11 Patients with a history of alcohol or drug abuse within the recent one year 6.12 Patients with a history or evidence of post-polycythemia vera myelofibrosis (post-PV MF), essential thrombocythemia, or MPN other than PV

7. Patients who received any other study treatment or concomitant medication with other study drug within 4 weeks prior to the first dose of study drug in this study or not recovered from any prior exposure to any other study drug.
8. Patients with symptomatic splenomegaly
9. Patients with circulating blasts in the peripheral blood within the last 12 weeks

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: 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-doaw 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.; Drug: P1101; The subjects will be treated with P1101(ropeginterferon alfa-2b), starting at a dose of 250 micrograms. The dose of P1101 will be increased to 350 micrograms 2 weeks later and to 500 micrograms another 2 weeks later, and then P1101 will be administered at a fixed dose of 500 micrograms throughout the treatment period. Although the dose may be reduced to the prior dose for reasons related to the safety or tolerability, the increased dose should be preferably maintained throughout the treatment period. The dose of P1101 will be increased or decreased appropriately depending on the pathological condition in the range up to 500 micrograms.; Other Names: Ropeginterferon alfa-2b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Week 24	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of achieving "phlebotomy-free complete hematologic response (CHR)" (the same criteria as for the primary efficacy endpoint) at both Week 12 and Week 24.		Week12, Week24
Time to achieve CHR		Up to Week24
Time to reach response maintenance dose (three consecutive doses of the same dose)		Up to Week24
Numbers of phlebotomy required and changes in numbers of phlebotomy required from baseline		Baseline, up to Week24
Time to first response in peripheral blood count (Hct, WBC, and PLT)		Up to Week24
Duration of response in peripheral blood count (Hct, WBC, and PLT)		Up to Week24
Improvement of symptoms assessed by MPN-SAF TSS at each visit	Rated on a scale of 0-10 on an 11-point scale, with 0 being no symptoms, 1 being the best, and 10 being the worst.	Up to Week24
Proportion of subjects without thrombotic or hemorrhagic events at Weeks 12 and 24		Week12, week24
Change from baseline to Week 24 in JAK2 V617F allele burden level		Baseline, week24
Collect and measure Pharmacokinetics (PK) at trough		Day1, Week2, Week4, Week6, Week8, Week10, Week12, Week14, Week16, Week18, Week20, Week22, Week24

Collaborators and Investigators

• Sponsor: PharmaEssentia Japan K.K.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Actual): July 26, 2024
• Study Completion (Actual): July 26, 2024

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Aspirin
• Other Study ID Numbers: A23-301

Drug and device information, study documents

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