Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance

NCT04285086 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: P1101 ET
• Study Type: interventional
• Target: 174
• Locations: 8 countries
• Sites: 65

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.

Conditions

Essential Thrombocythemia

Keywords

Essential Thrombocythemia; Ropeginterferon; P1101; PharmaEssentia; MPN; Myeloproliferative neoplasms; ET; JAK2; CALR; MPL; IFN

Outcome Measures

Primary Outcomes (4)

• Peripheral blood count remission

  platelets ≤400 x 10\^9/L AND white blood cells (WBC) \<9.5 x 10\^9/L

  month 9 and month 12

• Improvement or non-progression in disease-related signs

  splenomegaly

  month 9 and month 12

• Large symptoms improvement or maintain non-progression

  based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

  month 9 and month 12

• Absence of hemorrhagic or thrombotic events

  absence of hemorrhagic or thrombotic events

  month 9 and month 12

Study Arms (2)

Ropeginterferon alfa-2b (P1101)

EXPERIMENTAL

Pre-filled Syringe, Q2W, SC injection

Biological: Ropeginterferon alfa-2b

Anagrelide

ACTIVE COMPARATOR

Capsules, Daily, p.o.

Drug: Anagrelide

Interventions

Ropeginterferon alfa-2b BIOLOGICAL

Ropeginterferon alfa-2b (P1101) dosage: from 250 mcg to 500 mcg

Also known as: P1101

Ropeginterferon alfa-2b (P1101)

Anagrelide DRUG

Anagrelide dosage: 0.5 mg per capsule, according to label and physician's judgement

Anagrelide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• PharmaEssentia: lead

Study Sites (65)

Washington University School of Medicine - Division of Oncology

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2C1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

Peking University People's Hospital

Beijing, Beijing Municipality, China

Location

The First Affiliated Hospital, Chongqing Medical University

Chongqing, Chongqing Municipality, China

Location

NanFang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technolog

Wuhan, Hubei, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

Location

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, China

Location

Ruijin Hospital affiliated to Shanghai Jiao Tong University school of Medicine

Shanghai, Shanghai Municipality, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

The Second Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300211, China

Location

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Ehime University Hospital

Tōon, Ehime, 791-0204, Japan

Location

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0329, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

University of Miyazaki Hospital

Miyazaki, Miyazaki, 889-1692, Japan

Location

Kansai Medical University Hospital

Hirakata, Osaka, 573-1191, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Juntendo University Shizuoka Hospital

Izunokuni, Shizuoka, 410-2295, Japan

Location

Juntendo University Hospital

Bunkyo City, Tokyo, 113-8431, Japan

Location

Nippon Medical School Hospital

Bunkyo City, Tokyo, 113-8603, Japan

Location

NTT Medical Center Tokyo

Shinagawa City, Tokyo, 141-0022, Japan

Location

Tokyo Medical University Hospital

Shinjuku, Tokyo, 160-0023, Japan

Location

University of Yamanashi Hospital

Chūō, Yamanashi, 409-3898, Japan

Location

National University Hospital

Singapore, 119074, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Daegu Catholic University Hospital

Daegu, 30566, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

SoonChunHyang University Seoul Hospital

Seoul, 04401, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, 06591, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Chia-Yi Christian Hospital

Chiayi City, Chiayi County, 60002, Taiwan

Location

Chiayi Chang Gung Memorial Hospital

Chiayi City, Chiayi County, 61363, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, Kaohsiung City, 81362, Taiwan

Location

E-Da Cancer Hospital

Kaohsiung City, Kaohsiung City, 82445, Taiwan

Location

E-Da Hospital

Kaohsiung City, Kaohsiung City, 82445, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, New Taipei City, 22060, Taiwan

Location

Tainan Municipal An-Nan Hospital

Tainan, Tainan City, 70965, Taiwan

Location

Chi Mei Medical Center

Tainan, Tainan City, 71004, Taiwan

Location

Chi-Mei Hospital - Liouying Branch

Tainan, Tainan City, 73657, Taiwan

Location

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, Taipei City, 11101, Taiwan

Location

Taipei Municipal Wan Fang Hospital

Taipei, Taipei City, 11696, Taiwan

Location

Hualien Tzu Chi Hospital

Hualien City, 97002, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Tri-Service General Hospital

Taipei, 11449, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan, 33305, Taiwan

Location

Related Publications (2)

• Mesa R, Gill H, Zhang L, Jin J, Kirito K, Komatsu N, Qin A, Xiao Z, Tashi T, Shimoda K, Ohishi K, Chen S, Zuo X, Shirane S, Hu Y, Zhang S, Wang Y, Takenaka K, Ichii M, Xu N, Shih LY, Lim KH, Lee SE, Bae SH, Teo WZY, Maze D, Oh ST, Bose P, Sato T, Zagrijtschuk O, Lin S, Shih WJ, Mascarenhas J, Masarova L; SURPASS-ET Study Group. Ropeginterferon alfa-2b in hydroxyurea-intolerant or hydroxyurea-refractory essential thrombocythaemia (SURPASS ET): a multicentre, open-label, randomised, active-controlled, phase 3 study. Lancet Haematol. 2025 Nov;12(11):e862-e875. doi: 10.1016/S2352-3026(25)00264-9.

  PMID: 41193116 DERIVED

• Verstovsek S, Komatsu N, Gill H, Jin J, Lee SE, Hou HA, Sato T, Qin A, Urbanski R, Shih W, Zagrijtschuk O, Zimmerman C, Mesa RA. SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocythemia. Future Oncol. 2022 Sep;18(27):2999-3009. doi: 10.2217/fon-2022-0596. Epub 2022 Aug 4.

  PMID: 35924546 DERIVED

MeSH Terms

Conditions

Thrombocythemia, Essential; Myeloproliferative Disorders

Interventions

anagrelide

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Bone Marrow Diseases; Hemorrhagic Disorders

Study Officials

• Toshiaki Sato, MD/PhD

  PharmaEssentia Japan K.K.

  STUDY DIRECTOR

• Craig Zimmerman, PhD

  PharmaEssentia USA Corp.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Experimental Drug (Biological): Ropeginterferon alfa-2b (P1101), Q2W, SC injection Control Drug: Anagrelide, capsules, daily, p.o.

Study Record Dates

• First Submitted: February 23, 2020
• First Posted: February 26, 2020
• Study Start: August 25, 2020
• Primary Completion: November 12, 2024
• Study Completion (Estimated): August 31, 2029
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); JP (13); KR (7); CA (3); US (3); SG (2); CN (15); TW (21)