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.

PharmaEssentia65 sites in 8 countries174 target enrollmentAugust 25, 2020

ConditionsEssential Thrombocythemia

InterventionsRopeginterferon alfa-2b Anagrelide

DrugsRopeginterferon alfa-2b Anagrelide

Overview

Phase: Phase 3
Intervention: Ropeginterferon alfa-2b
Conditions: Essential Thrombocythemia
Sponsor: PharmaEssentia
Enrollment: 174
Locations: 65
Primary Endpoint: Peripheral blood count remission
Status: Active, not recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 25, 2020

End Date

August 31, 2029

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

PharmaEssentia

Responsible Party

Sponsor

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 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

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)