Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
Inclusion Criteria:
1. Male or female subjects ≥18 years old. 2. 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. 3. 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. 4. 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. 5. 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. 6. Platelets >450 x 10^9/L at screening. 7. WBC >10 x 10^9/L at screening. 8. HGB ≥11 g/dL at screening for males and 10 g/dL at screening for females. 9. Neutrophil count ≥1.0 x 10^9/L at screening. 10. 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. 11. Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation) 12. 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. 13. Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study.Exclusion Criteria:
1. Any subject requiring a legally authorized representative. 2. Any contraindications or hypersensitivity to IFN-α or ANA and their excipients. 3. 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. 4. 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. 5. History of major organ transplantation. 6. Pregnant or lactating females. 7. 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: 1. 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) 2. 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. 3. Infections with systemic manifestations (e.g., bacterial, fungal, or human immunodeficiency virus [HIV], except hepatitis B [HBV] and/or hepatitis C [HCV], at screening) 4. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) 5. 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. 6. History or presence of clinically significant neurodegenerative diseases. 7. History of any malignancy within 5 years (except Stage 0 chronic lymphocytic leukemia, basal cell, squamous cell, and superficial melanoma) 8. History of alcohol or drug abuse within the last year. 9. History or evidence of any other MPN. 8. 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. 9. Subjects with documented ANA resistance or intolerance (see Appendix 8 for definition).Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04285086 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
PharmaEssentia |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Toshiaki Sato, MD/PhDCraig Zimmerman, PhD |
Principal Investigator Affiliation | PharmaEssentia Japan K.K.PharmaEssentia USA Corp. |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry, Other |
Overall Status | Recruiting |
Countries | Canada, China, Hong Kong, Japan, Korea, Republic of, Singapore, Taiwan, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Essential Thrombocythemia |
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. 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.
Arms
Experimental: Ropeginterferon alfa-2b (P1101)
Pre-filled Syringe, Q2W, SC injection
Active Comparator: Anagrelide
Capsules, Daily, p.o.
Interventions
Biological: - Ropeginterferon alfa-2b
Ropeginterferon alfa-2b (P1101) dosage: from 250 mcg to 500 mcg
Drug: - Anagrelide
Anagrelide dosage: 0.5 mg per capsule, according to label and physician's judgement
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
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Washington University School of Medicine - Division of Oncology
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Mount Sinai Medical Center
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Weill Medical College of Cornell University
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MD Anderson Cancer Center
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University of Texas Health Science Center at San Antonio
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University of Utah
Salt Lake City, Utah, 84112
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Address
Froedtert Hospital and Medical College of Wisconsin
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International Sites
Status
Recruiting
Address
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Status
Not yet recruiting
Address
Princess Margaret Hospital
Toronto, Ontario, M5G 2C1
Status
Not yet recruiting
Address
Jewish General Hospital
Montréal, Quebec, H3T 1E2
Status
Recruiting
Address
Peking Union Medical College Hospital
Beijing, Beijing,
Status
Recruiting
Address
Peking University People's Hospital
Beijing, Beijing,
Status
Recruiting
Address
The First Affiliated Hospital, Chongqing Medical University
Chongqing, Chongqing,
Status
Recruiting
Address
NanFang Hospital of Southern Medical University
Guangzhou, Guangdong,
Status
Recruiting
Address
Union Hospital Tongji Medical College Huazhong University of Science and Technolog
Wuhan, Hubei,
Status
Recruiting
Address
Zhongnan Hospital of Wuhan University
Wuhan, Hubei,
Status
Recruiting
Address
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu,
Status
Recruiting
Address
Shengjing Hospital of China Medical University
Shenyang, Liaoning,
Status
Recruiting
Address
Shaanxi Provincial People's Hospital
Xi'an, Shaanxi,
Status
Recruiting
Address
Qilu Hospital of Shandong University
Jinan, Shandong,
Status
Recruiting
Address
Ruijin Hospital affiliated to Shanghai Jiao Tong University school of Medicine
Shanghai, Shanghai,
Status
Recruiting
Address
West China Hospital, Sichuan University
Chengdu, Sichuan,
Status
Recruiting
Address
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin,
Status
Recruiting
Address
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang,
Status
Recruiting
Address
Queen Mary Hospital
Hong Kong, ,
Status
Recruiting
Address
Ehime University Hospital
Toon, Ehime, 791-0204
Status
Recruiting
Address
Kitasato University Hospital
Sagamihara, Kanagawa, 252-0329
Status
Recruiting
Address
Mie University Hospital
Tsu, Mie, 514-8507
Status
Recruiting
Address
University of Miyazaki Hospital
Miyazaki City, Miyazaki, 889-1692
Status
Recruiting
Address
Kansai Medical University Hospital
Hirakata, Osaka, 573-1191
Status
Recruiting
Address
Kindai University Hospital
Osakasayama, Osaka, 589-8511
Status
Recruiting
Address
Osaka University Hospital
Suita, Osaka, 565-0871
Status
Recruiting
Address
Juntendo University Shizuoka Hospital
Izunokuni, Shizuoka, 410-2295
Status
Recruiting
Address
Juntendo University Hospital
Bunkyo City, Tokyo, 113-8431
Status
Recruiting
Address
Nippon Medical School Hospital
Bunkyo City, Tokyo, 113-8603
Status
Recruiting
Address
NTT Medical Center Tokyo
Shinagawa City, Tokyo, 141-0022
Status
Recruiting
Address
Tokyo Medical University Hospital
Shinjuku City, Tokyo, 160-0023
Status
Recruiting
Address
University of Yamanashi Hospital
Chuo, Yamanashi, 409-3898
Status
Recruiting
Address
Gachon University Gil Medical Center
Incheon, , 21565
Status
Recruiting
Address
Seoul National University Hospital
Seoul, , 03080
Status
Recruiting
Address
Severance Hospital, Yonsei University Health System
Seoul, , 03722
Status
Recruiting
Address
SoonChunHyang University Seoul Hospital
Seoul, , 04401
Status
Recruiting
Address
Konkuk University Hospital
Seoul, , 05030
Status
Recruiting
Address
Samsung Medical Center
Seoul, , 06351
Status
Recruiting
Address
Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul, , 06591
Status
Recruiting
Address
Korea University Guro Hospital
Seoul, , 08308
Status
Recruiting
Address
National University Hospital
Singapore, , 119074
Status
Recruiting
Address
Singapore General Hospital
Singapore, , 169608
Status
Recruiting
Address
Chiayi Chang Gung Memorial Hospital
Puzi City, Chiayi County, 61363
Status
Not yet recruiting
Address
Hualien Tzu Chi Hospital
Hualien City, , 97002
Status
Recruiting
Address
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, , 80756
Status
Recruiting
Address
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, , 83301
Status
Recruiting
Address
China Medical University Hospital
Taichung City, , 40447
Status
Recruiting
Address
National Cheng Kung University Hospital
Tainan City, , 70403
Status
Recruiting
Address
National Taiwan University Hospital
Taipei City, , 10002
Status
Recruiting
Address
Mackay Memorial Hospital
Taipei City, , 10449
Status
Recruiting
Address
Taipei Veterans General Hospital
Taipei City, , 11217
Status
Recruiting
Address
Tri-Service General Hospital
Taipei City, , 11449
Status
Recruiting
Address
Linkou Chang Gung Memorial Hospital
Taoyuan City, , 33305