Clinical trial NCT06002490: A Study to Evaluate P1101 in Japanese PV Patients
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycythemia Vera (PV)
Keywords: Myeloproliferative Neoplasms
Lead sponsor: PharmaEssentia Japan K.K.
Sponsor class: INDUSTRY
First posted: 2023-08-21
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: 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.
timeFrame: Week12, Week24
measure: Time to achieve CHR
timeFrame: Up to Week24
measure: Time to reach response maintenance dose (three consecutive doses of the same dose)
timeFrame: Up to Week24
measure: Numbers of phlebotomy required and changes in numbers of phlebotomy required from baseline
timeFrame: Baseline, up to Week24
measure: Time to first response in peripheral blood count (Hct, WBC, and PLT)
timeFrame: Up to Week24
measure: Duration of response in peripheral blood count (Hct, WBC, and PLT)
timeFrame: Up to Week24
measure: Improvement of symptoms assessed by MPN-SAF TSS at each visit
timeFrame: Up to Week24
measure: Proportion of subjects without thrombotic or hemorrhagic events at Weeks 12 and 24
timeFrame: Week12, week24
measure: Change from baseline to Week 24 in JAK2 V617F allele burden level
timeFrame: Baseline, week24
measure: Collect and measure Pharmacokinetics (PK) at trough
timeFrame: Day1, Week2, Week4, Week6, Week8, Week10, Week12, Week14, Week16, Week18, Week20, Week22, Week24
Other outcomes:
Locations:
city: Mie
country: Japan
facility: Mie University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Osaka
country: Japan
facility: Kansai Medical University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Yamanashi
country: Japan
facility: University of Yamanashi Hospital
Study officials:
References: