Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance (SURPASS ET)
Essential Thrombocythemia
About this trial
This is an interventional treatment trial for Essential Thrombocythemia focused on measuring Essential Thrombocythemia, Ropeginterferon, P1101, PharmaEssentia
Eligibility Criteria
Inclusion Criteria:
- 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 14 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)
- 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
Exclusion Criteria:
- Any subject requiring a legally authorized representative
- 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
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, or previous suicide attempts or at any risk of suicide at screening, in the judgement of the Investigator
- History or presence of clinically significant neurodegenerative 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
- 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
- Subjects with documented ANA resistance or intolerance (see Appendix 8 for definition).
Sites / Locations
- Mayo ClinicRecruiting
- University of Kansas Cancer CenterRecruiting
- Washington University School of Medicine - Division of OncologyRecruiting
- Mount Sinai Medical CenterRecruiting
- Weill Medical College of Cornell UniversityRecruiting
- MD Anderson Cancer CenterRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- University of UtahRecruiting
- Froedtert Hospital and Medical College of WisconsinRecruiting
- St. Paul's HospitalRecruiting
- Princess Margaret Hospital
- Jewish General Hospital
- Peking Union Medical College HospitalRecruiting
- Peking University People's HospitalRecruiting
- The First Affiliated Hospital, Chongqing Medical UniversityRecruiting
- NanFang Hospital of Southern Medical UniversityRecruiting
- Union Hospital Tongji Medical College Huazhong University of Science and TechnologRecruiting
- Zhongnan Hospital of Wuhan UniversityRecruiting
- The First Affiliated Hospital of Soochow UniversityRecruiting
- Shengjing Hospital of China Medical UniversityRecruiting
- Shaanxi Provincial People's HospitalRecruiting
- Qilu Hospital of Shandong UniversityRecruiting
- Ruijin Hospital affiliated to Shanghai Jiao Tong University school of MedicineRecruiting
- West China Hospital, Sichuan UniversityRecruiting
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting
- The First Affiliated Hospital, College of Medicine, Zhejiang UniversityRecruiting
- Queen Mary HospitalRecruiting
- Ehime University HospitalRecruiting
- Kitasato University HospitalRecruiting
- Mie University HospitalRecruiting
- University of Miyazaki HospitalRecruiting
- Kansai Medical University HospitalRecruiting
- Kindai University HospitalRecruiting
- Osaka University HospitalRecruiting
- Juntendo University Shizuoka HospitalRecruiting
- Juntendo University HospitalRecruiting
- Nippon Medical School HospitalRecruiting
- NTT Medical Center TokyoRecruiting
- Tokyo Medical University HospitalRecruiting
- University of Yamanashi HospitalRecruiting
- Gachon University Gil Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- Severance Hospital, Yonsei University Health SystemRecruiting
- SoonChunHyang University Seoul HospitalRecruiting
- Konkuk University HospitalRecruiting
- Samsung Medical CenterRecruiting
- Seoul St. Mary's Hospital, The Catholic University of KoreaRecruiting
- Korea University Guro HospitalRecruiting
- National University HospitalRecruiting
- Singapore General HospitalRecruiting
- Chiayi Chang Gung Memorial HospitalRecruiting
- Hualien Tzu Chi Hospital
- Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
- Kaohsiung Chang Gung Memorial HospitalRecruiting
- China Medical University HospitalRecruiting
- National Cheng Kung University HospitalRecruiting
- National Taiwan University HospitalRecruiting
- Mackay Memorial HospitalRecruiting
- Taipei Veterans General HospitalRecruiting
- Tri-Service General HospitalRecruiting
- Linkou Chang Gung Memorial HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Ropeginterferon alfa-2b (P1101)
Anagrelide
Pre-filled Syringe, Q2W, SC injection
Capsules, Daily, p.o.