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

Essential Thrombocythemia Clinical Trial

— SURPASS ET  

Official title:

A Phase 3, Open-Label, Multicenter, Randomized, Active-controlled Study to Assess PK and Compare the Efficacy, Safety, and Tolerability of P1101 vs Anagrelide as 2nd Line Therapy for Essential Thrombocythemia (SURPASS ET): The Core Study and Its Extension Study.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04285086
• Other study ID #: P1101 ET
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 25, 2020
• Est. completion date: December 30, 2025

Study information

• Verified date: November 2023
• Source: PharmaEssentia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 174
• Est. completion date: December 30, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 7 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-a 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

6. Previous suicide attempts or at any risk of suicide at screening, in the judgement of the Investigator

7. History or presence of clinically significant neurologic diseases

8. History of any malignancy within 5 years (except Stage 0 chronic lymphocytic leukemia, basal cell, squamous cell, and superficial melanoma)

9. History of alcohol or drug abuse within the last year

10. History or evidence of any other MPN

11. History of splenectomy

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).

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

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

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital, Chongqing Medical University	Chongqing	Chongqing
China	NanFang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Ruijin Hospital affiliated to Shanghai Jiao Tong University school of Medicine	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technolog	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Shaanxi Provincial People's Hospital	Xi'an	Shaanxi
Hong Kong	Queen Mary Hospital	Hong Kong
Japan	Juntendo University Hospital	Bunkyo City	Tokyo
Japan	Nippon Medical School Hospital	Bunkyo City	Tokyo
Japan	University of Yamanashi Hospital	Chuo	Yamanashi
Japan	Kansai Medical University Hospital	Hirakata	Osaka
Japan	Juntendo University Shizuoka Hospital	Izunokuni	Shizuoka
Japan	University of Miyazaki Hospital	Miyazaki City	Miyazaki
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Kitasato University Hospital	Sagamihara	Kanagawa
Japan	NTT Medical Center Tokyo	Shinagawa City	Tokyo
Japan	Tokyo Medical University Hospital	Shinjuku City	Tokyo
Japan	Osaka University Hospital	Suita	Osaka
Japan	Ehime University Hospital	Toon	Ehime
Japan	Mie University Hospital	Tsu	Mie
Korea, Republic of	Daegu Catholic University Hospital	Daegu
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital, The Catholic University of Korea	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	SoonChunHyang University Seoul Hospital	Seoul
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Taiwan	Chia-Yi Christian Hospital	Chiayi City	Chiayi County
Taiwan	Chiayi Chang Gung Memorial Hospital	Chiayi City	Chiayi County
Taiwan	Hualien Tzu Chi Hospital	Hualien City
Taiwan	E-Da Cancer Hospital	Kaohsiung City
Taiwan	E-Da Hospital	Kaohsiung City
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung City
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung City
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung City
Taiwan	Chi Mei Medical Center	Tainan City
Taiwan	Chi-Mei Hospital - Liouying Branch	Tainan City
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Tainan Municipal An-Nan Hospital	Tainan City
Taiwan	Mackay Memorial Hospital	Taipei City
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei City
Taiwan	Taipei Municipal Wan Fang Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Tri-Service General Hospital	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan City
United States	MD Anderson Cancer Center	Houston	Texas
United States	Washington University School of Medicine - Division of Oncology	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
PharmaEssentia

Countries where clinical trial is conducted

United States,  Canada,  China,  Hong Kong,  Japan,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Improvement or non-progression in disease-related signs	splenomegaly	month 9 and month 12
Primary	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
Primary	Absence of hemorrhagic or thrombotic events	absence of hemorrhagic or thrombotic events	month 9 and month 12