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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 8
- 主要终点
- Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12
研究概览
简要总结
This is a Phase 2 single arm study to investigate efficacy and safety of P1101 for adult Japanese patients with PV.
详细描述
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..
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Neutrophil count ≥1.5 x 10^9/L at screening
- •Serum creatinine ≤1.5 x ULN at screening
- •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.).
- •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
- •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
排除标准
- •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
- •7-2.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)
- •History of any malignancy within for the past 5 years
- •History of alcohol or drug abuse within the last year
- •History or evidence of post polycythemia vera-myelofibrosis (PPV-MF), essential thrombocythemia, or any non-PV MPN
- •Presence of circulating blasts in the peripheral blood within the last 3 months
- •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
研究组 & 干预措施
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.
干预措施: P1101 (Drug)
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.
干预措施: Low-dose aspirin (Drug)
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.
干预措施: Phlebotomy (Procedure)
结局指标
主要结局
Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12
时间窗: 12 months
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
次要结局
- Changes in WBC Count From Baseline(Baseline, 3 months, 6 months, 9 months and 12 months)
- Changes in Hct From Baseline(Baseline, 3 months, 6 months, 9 months and 12 months)
- Duration of Response Maintenance(Up to 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)
- Time Required to First Response(Up to 12 months)
- Proportion of Subjects Without Thrombotic or Hemorrhagic Events(Up to 12 months)
- PK of P1101(Up to 12 months)
- Change of JAK2 Mutant Allelic Burden Over Time vs. Baseline(Baseline, 3 months, 6 months, 9 months and 12 months)