A Study to Evaluate the Efficacy and Safety of Ropeginterferon Alfa-2b in Essential Thrombocythaemia Patients
NCT Number: NCT06514807
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Essential Thrombocythaemia
Interventions: DRUG: Ropeginterferon alfa-2b (BESREMi®)
Sponsor: AOP Orphan Pharmaceuticals AG
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 117
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2023-12-04
Completion Date: 2028-03-15
Locations: University Hospital Graz, Department of Internal Medicine, Clinical Department of Hematology, Graz, Styria, 8036, Austria|Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology), Innsbruck, Tyrol, 6020, Austria|Ordensklinikum Linz GmbH Elisabethinen Hospital, Department of Internal Medicine I - Hemato-Oncology, Linz, Upper Austria, 4020, Austria|Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology, Vienna, Austria|University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology, Brno, 625 00, Czechia|University Hospital Kralovske Vinohrady, Clinic of Internal Hematology, Prague, 10000, Czechia|Saint-Louis Hospital, Department of Adult Hematology, Paris, 75010, France|Bordeaux University Hospital, Haut-Leveque Hospital, Pessac, 33600, France|Centre Hospitalier Universitaire De Poitiers, Poitiers, 86000, France|University Hospital Aachen, Clinic of Oncology, Hematology and Stem Cell Transplantation (Medical Clinic IV), Aachen, 52074, Germany|University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology, Halle, 06120, Germany|Hannover Medical School, Clinic for haematology, haemostaseology, oncology and stem cell transplantation, Hannover, 30625, Germany|University Hospital Mannheim, Medical Clinic III, Hematology and Internistic Oncology, Mannheim, 68167, Germany|Johannes Wesling Hospital Minden, Department of Oncology and Hematology, Minden, 32429, Germany|University Hospital Ulm, Center for Internal Medicine, Clinic of Internal Medicine III, Department of Hematology, Oncology, Rheumatology, Infectious Diseases, Ulm, 89081, Germany|General Hospital of Athens Alexandra, Therapeutic Clinic, Department of Therapeutics, Athens, 11528, Greece|University General Hospital "Attikon", Athens, PC 12462, Greece|Semmelweis University, Department of Internal Medicine and Haematology, Division of Hematology, Budapest, H-1088, Hungary|University of Debrecen Clinical Center, Clinic of Internal Medicine, Department of Hematology, Debrecen, 4032, Hungary|Polyclinic S. Orsola-Malpighi, Bologna, 40138, Italy|Careggi University Hospital, Department of Hematology, Florence, 50134, Italy|Umberto I Polyclinic of Rome, Rome, 00161, Italy|University Polyclinic Foundation "Agostino Gemelli" - IRCCS, Service of Hematology, Rome, 00168, Italy|University Hospital City of Health and Science of Turin - Hospital Molinette, Complex Structure of Hematology - U, Turin, 10126, Italy|University Teaching Centre, Hematology and Transplantology Clinic, Gdansk, 80-952, Poland|Pratia Oncology Katowice, Katowice, 40-519, Poland|Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department, Kraków, 31-501, Poland|Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz, Department of Hematooncology with Subdivision of Daytime Chemotherapy, Łódź, 93-513, Poland|Onco Card Srl, Brasov, 500052, Romania|"Prof. Dr. Ion Chiricuta" Institute of Oncology, Hematology Department, Cluj-Napoca, 400015, Romania|Fundeni Clinical Institute, Center for Hematology and Bone Marrow Transplantation, Crisan, 022328, Romania|Iasi Regional Institute of Oncology, Department of Hematology, Iasi, 700483, Romania|University Hospital Germans Trias i Pujol, Badalona, 08916, Spain|Hospital Clinic of Barcelona, Department of Hematology, Barcelona, 08036, Spain|University Hospital Ramon y Cajal, Hematology Service, Madrid, 28034, Spain|Morales Meseguer University General Hospital, Murcia, 30008, Spain

Summary:
The primary objective of this study is to assess the efficacy of ropeginterferon alfa-2b in patients with ET who need cytoreductive treatment but are intolerant or refractory to, and/or ineligible for cytoreductive treatments approved and available for the treatment of ET (i.e., HU, ANA, BUS, and PB, when they are available and approved for ET treatment).

Ropeginterferon alfa-2b is currently the only interferon authorised as a cytoreductive treatment of a myeloproliferative neoplasm (MPN), and the long-term treatment data from its comprehensive clinical development program show its efficacy in the induction of haematologic remission, resolution of disease-associated symptoms, disease-modifying effect, as well as its favourable safety profile (Gisslinger et al., 2020; Kiladjian et al. 2022).

Available clinical data and experience show that ropeginterferon alfa-2b normalises various haematological parameters, including platelets. In addition, suppression of the malignant clone causing ET may be achieved, at least after long-term treatment, which is expected to possibly defer the onset of, or avoid long-term sequelae of ET.

Primary Outcome Measures: Durable (for at least 3 months) peripheral blood count remission, PLTs ≤400 x 109/L AND WBC \<10 x 109/L, At month 12|Absence of haemorrhagic or thrombotic events and absence of disease progression*, \*Progression is defined as conversion from asymptomatic to symptomatic splenomegaly or clinically relevant progression of spleen size at the Investigator's discretion, respectively., At month 12|Absence or Non-progression* in disease-related signs, \*Progression is defined as conversion from asymptomatic to symptomatic splenomegaly or clinically relevant progression of spleen size at the Investigator's discretion, respectively., At month 12|Durable (for at least 3 months) large symptoms improvement or maintenance of non-progression based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)#, # Large symptoms improvement for ET patients is defined as follows:

* Baseline TSS ≥20: 10-points reduction in TSS
* Baseline TSS 15-19, inclusive: 5-points reduction in TSS
* Baseline TSS 10-14, inclusive: TSS decreases to ≤10
* Baseline TSS \<10: TSS stays \<10, At month 12
Secondary Outcome Measures: Response at month 9, 18, 24, 30 and 36, Month 9, 18, 24, 30 and 36|Longitudinal changes in the ELN response rates over 12 months, up to 36 months|Time to first response (as defined by ELN criteria), up to 36 months|Duration of first response (as defined by ELN criteria), up to 36 months|Duration of first durable response (as defined by ELN criteria), up to 36 months|Time to first peripheral blood count remission response, up to 36 months|Duration of first durable peripheral blood count remission response, up to 36 months|Occurrence of thromboembolic and bleeding events response, up to 36 months|Occurrence of disease progression response, up to 36 months|Symptomatic improvement assessed by EQ-5D-5L questionnaire response, up to 36 months|Symptomatic improvement assessed by the 10-item MPN-SAF TSS, up to 36 months|Change in inflammation markers over time, up to 36 months|Change in CALR, MPL, or JAK2 allelic burden over time, up to 36 months
Other Outcome Measures: Safety endpoints, Adverse events (AEs), according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), up to 36 months