Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance
- Conditions
- Essential Thrombocythemia
- Interventions
- Biological: Ropeginterferon alfa-2b
- Registration Number
- NCT04285086
- Lead Sponsor
- PharmaEssentia
- Brief Summary
This is a Phase 3 open-label, multicenter, randomized, active-controlled study designed to compare the efficacy and safety and tolerability of P1101 compared with ANA after 12 months of treatment as second-line therapy for subjects with ET who have had a suboptimal or failed response to HU.
- Detailed Description
PharmaEssentia Corporation is developing a pegylated (PEG) IFN-α product, P1101, for the treatment of ET.
Available clinical data and experience with P1101 in PV shows that the compound, with proper dose modifications, is effective in controlling disease in a significant proportion of subjects with ET. Further, its increased serum half-life presents distinct advantages for ET treatment over that of standard IFN-α and other available PEG IFN-α therapy. This pivotal Phase 3 study will establish the efficacy and safety of P1101 in ET subjects.
In core study phase, the enrolled subjects will be randomized into two arms, the test arm is P1101, the control arm is ANA. The overall duration for each eligible patient is 14 months, including screening (1 month), treatment (12 months) and follow-up (1 month) period. Efficacy evaluations, safety assessments, and PK and immunogenicity evaluations of P1101 will be performed.
Evaluation of efficacy will include clinical laboratory assessments, allelic burden measurements of CALR, JAK-2, and MPL, spleen size measurements, bone marrow sampling, EQ-5D-3L, and MPN-SAF TSS completion.
Evaluation of safety will include assessing vital signs, clinical safety laboratory tests, physical examinations, ECG evaluation, heart ECHO, lung X-ray, ECOG performance status, ocular examination, and AEs.
Subjects who completed the end of treatment (EoT) and safety follow-up (EoS) visits of the SURPASS ET study and may benefit from P1101 therapy have the opportunity to receive P1101 treatment.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 174
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Male or female subjects ≥18 years old
-
Subjects diagnosed with high-risk ET (either older than 60 years and JAK2V617-positive at screening, or having disease-related thrombosis or hemorrhage in the past), diagnosed according to the World Health Organization (WHO) 2016 criteria
-
Subjects have received prior HU for ET, while the washout between the last dose of HU and randomization should not be shorter than 7 days
-
Interferon treatment-naïve, or anti-P1101 binding antibody negative at screening and the washout between last dose of interferon and randomization should not be shorter than 14 days.
-
Documented resistance/intolerance to prior HU for ET, referencing modified ELN criteria (Barosi, et al, 2007), whereby at least one of the following criteria is met:
Platelet count >600 x 10^9/L at ≥2 g/day (or ≥2.5 g/day if subject body weight >80 kg) or maximally tolerated dose if <2 g/day after at least 3 months of HU, or Platelet count >400 x 10^9/L and WBC count <2.5 x 10^9/L at any dose and any duration of HU, or Platelet count >400 x 10^9/L and hemoglobin (HGB) <10 g/dL at any dose and any duration of HU, or Presence of HU-related toxicities at any dose and any duration of therapy (e.g., leg ulcers, mucocutaneous manifestations, pneumonitis, or HU-related fever), or Platelet count >450 x 10^9/L at any dose and any duration of HU. The actual dose and duration of HU must be recorded on the eCRF. Moreover, if patient received one dose of HU, the reason why subject was judged to be HU resistance/intolerance must be recorded on the eCRF.
-
Platelets >450 x 10^9/L at screening
-
WBC >10 x 10^9/L at screening
-
HGB ≥11 g/dL at screening for males and 10 g/dL at screening for females
-
Neutrophil count ≥1.0 x 10^9/L at screening
-
Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), prothrombin time (PT) (international normalized ratio, INR) ≤1.5 x ULN, albumin >3.5 g/dL, alanine aminotransferase ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at screening
-
Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation)
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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, and females must agree to not breastfeed during the study
-
Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study
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Any subject requiring a legally authorized representative
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Any contraindications or hypersensitivity to IFN-α or ANA and their excipients
-
Known risk factors for QT-prolongation (e.g., congenital long QT, known history of acquired QT-prolongations). Medications that can prolong QTc and induce hypokalemia will not be allowed in the study.
-
Co-morbidity with severe or serious condition that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol, including significant cardiac disease (including New York Heart Association Class III-IV congestive heart failure and clinically significant arrhythmias) and pulmonary hypertension
-
History of major organ transplantation
-
Pregnant or lactating females
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Subjects with any other significant medical conditions that, in the opinion of the Investigator, would compromise the results of the study or may impair compliance with the requirements of the protocol, including but not limited to:
- Documented autoimmune disease at screening or in the history (e.g., thyroid dysfunction, hepatitis, idiopathic thrombocytopenic purpura, scleroderma, psoriasis, or any arthritis of autoimmune origin)
- Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol
- Infections with systemic manifestations (e.g., bacterial, fungal, or human immunodeficiency virus [HIV], except hepatitis B [HBV] and/or hepatitis C [HCV], at screening)
- Evidence of severe retinopathy (e.g., cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension)
- History or presence of clinically relevant depression
- Previous suicide attempts or at any risk of suicide at screening, in the judgement of the Investigator
- History or presence of clinically significant neurologic diseases
- History of any malignancy within 5 years (except Stage 0 chronic lymphocytic leukemia, basal cell, squamous cell, and superficial melanoma)
- History of alcohol or drug abuse within the last year
- History or evidence of any other MPN
- History of splenectomy
-
Use of any investigational drug <4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent
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Subjects with documented ANA resistance or intolerance (see Appendix 8 for definition).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ropeginterferon alfa-2b (P1101) Ropeginterferon alfa-2b Pre-filled Syringe, Q2W, SC injection Anagrelide Anagrelide Capsules, Daily, p.o.
- Primary Outcome Measures
Name Time Method Peripheral blood count remission month 9 and month 12 platelets ≤400 x 10\^9/L AND white blood cells (WBC) \<9.5 x 10\^9/L
Large symptoms improvement or maintain non-progression month 9 and month 12 based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Improvement or non-progression in disease-related signs month 9 and month 12 splenomegaly
Absence of hemorrhagic or thrombotic events month 9 and month 12 absence of hemorrhagic or thrombotic events
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (65)
University of Yamanashi Hospital
🇯🇵Chuo, Yamanashi, Japan
Ehime University Hospital
🇯🇵Toon, Ehime, Japan
Mie University Hospital
🇯🇵Tsu, Mie, Japan
Juntendo University Shizuoka Hospital
🇯🇵Izunokuni, Shizuoka, Japan
Juntendo University Hospital
🇯🇵Bunkyo City, Tokyo, Japan
Chi-Mei Hospital - Liouying Branch
🇨🇳Tainan City, Taiwan
NTT Medical Center Tokyo
🇯🇵Shinagawa City, Tokyo, Japan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
China Medical University Hospital
🇨🇳Taichung City, Taiwan
Chi Mei Medical Center
🇨🇳Tainan City, Taiwan
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
Tainan Municipal An-Nan Hospital
🇨🇳Tainan City, Taiwan
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
SoonChunHyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Mackay Memorial Hospital
🇨🇳Taipei City, Taiwan
National University Hospital
🇸🇬Singapore, Singapore
Washington University School of Medicine - Division of Oncology
🇺🇸Saint Louis, Missouri, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital, Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Union Hospital Tongji Medical College Huazhong University of Science and Technolog
🇨🇳Wuhan, Hubei, China
NanFang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Ruijin Hospital affiliated to Shanghai Jiao Tong University school of Medicine
🇨🇳Shanghai, Shanghai, China
Shaanxi Provincial People's Hospital
🇨🇳Xi'an, Shaanxi, China
The Second Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
🇨🇳Tianjin, Tianjin, China
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Kitasato University Hospital
🇯🇵Sagamihara, Kanagawa, Japan
University of Miyazaki Hospital
🇯🇵Miyazaki City, Miyazaki, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Kansai Medical University Hospital
🇯🇵Hirakata, Osaka, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Daegu Catholic University Hospital
🇰🇷Daegu, Korea, Republic of
Nippon Medical School Hospital
🇯🇵Bunkyo City, Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Tokyo Medical University Hospital
🇯🇵Shinjuku City, Tokyo, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital, The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Chia-Yi Christian Hospital
🇨🇳Chiayi City, Chiayi County, Taiwan
Singapore General Hospital
🇸🇬Singapore, Singapore
Chiayi Chang Gung Memorial Hospital
🇨🇳Chiayi City, Chiayi County, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung City, Taiwan
E-Da Cancer Hospital
🇨🇳Kaohsiung City, Taiwan
Hualien Tzu Chi Hospital
🇨🇳Hualien City, Taiwan
E-Da Hospital
🇨🇳Kaohsiung City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
🇨🇳Taipei City, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Taipei Municipal Wan Fang Hospital
🇨🇳Taipei City, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan City, Taiwan