polycythemia vera (PV)
Conditions
Interventions
investigational material(s)
Generic name etc : Ropeginterferonum alfa-2b
INN of investigational material : ropeginterferonum alfa-2b
Therapeutic category code : 429 Other antitumor agents
Dosage and A
Sponsors
PharmaEssentia Japan K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients more than or equal to 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 naive 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 less than45%) - frequent need of phlebotomy (more than one phlebotomy within last month prior entering the study) - platelet counts greater than 1,000,000/microliter (for two measurements within the month prior treatment start) - leukocytosis (WBC greater than 10,000/microliter for two measurements within the month prior treatment start) 6. Adequate hepatic function defined as bilirubin less than or equal to 1.5 x upper limit normal (ULN), international normalized ratio (INR) less than or equal to 1.5 x ULN, albumin more than 3.5 g/dL, alanine aminotransferase (ALT) less than or equal to 2.0 x ULN, aspartate aminotransferase (AST) less than or equal to 2.0 x ULN at screening 7. Hemoglobin (HGB) more than or equal to 10 g/dL at screening 8. Neutrophil count more than or equal to 1,500/microliter at screening 9. Serum creatinine less than or equal to 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 less than10] 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 IFN-alpha therapy). 11. Males and females of childbearing potential, as well as all women less than 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
Exclusion criteria: 1. Patients with symptomatic splenomegaly 2. Previous use of IFN-alpha 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 more than 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 less than 4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety efficacy Proportion of subjects achieving durable phlebotomy-free complete hematological response (CHR) at Month 12. The primary efficacy outcome measure is the proportion of subjects achieving durable phlebotomy-free complete hematologic response (CHR) at Month 12. Durable phlebotomy-free CHR is defined as any subject achieving phlebotomy-free CHR at Month 9 and maintaining the response up to Month 12. A responder in sense of a primary outcome measure is a subject who has met all the following criteria at the time points: - Hematocrit less than 45% phlebotomy-free (absence of phlebotomy during the previous 3 months) - Platelet count less than or equal to 400,000/microliter, - WBC count less than or equal to 10,000/microliter | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy pharmacokinetics - Changes in Hct, WBC, Plt count and spleen size from baseline- Time to requiring no phlebotomy - Time required to first response - Duration of response maintenance - Proportion of subjects without thrombotic or hemorrhagic events - Change of JAK2 V617F mutant allelic burden over time vs. baseline - PK of P1101 | — |
Countries
Japan
Outcome results
None listed