A Study to Evaluate the Efficacy and Safety of Ropeginterferon Alfa-2b in Essential Thrombocythaemia Patients

NCT06514807 | Active Not Recruiting Phase 3

• 1 other identifier: ROP-ET
• Study Type: interventional
• Target: 117
• Locations: 10 countries
• Sites: 36

Brief 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.

Conditions

Essential Thrombocythaemia

Keywords

Ropeginterferon alfa-2b; essential thrombocythaemia; intolerant to cytoreductive treatment; refractory to cytoreductive treatment; not eligible for other cytoreductive treatments; JAK2; CALR; MPL mutation status; BESREMi; Thrombocythaemia

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (13)

• 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

Other Outcomes (1)

• Safety endpoints

  up to 36 months

Study Arms (1)

Ropeginterferon alfa-2b (tradename BESREMi®)

EXPERIMENTAL

Ropeginterferon alfa-2b (tradename BESREMi®) 250 micrograms/0.5 mL or 500 micrograms/0.5 ml solution for injection in pre-filled pen. Ropeginterferon alfa-2b will be administered subcutaneously every 2 weeks at a dose of 125 µg / 250 µg / 500 µg per injection (depends on the optimal disease response) for up to 36 months of treatment.

Drug: Ropeginterferon alfa-2b (BESREMi®)

Interventions

Ropeginterferon alfa-2b (BESREMi®) DRUG

Ropeginterferon alfa-2b 250 micrograms/0.5 mL or 500 micrograms/0.5 ml solution for injection in pre-filled pen.

Ropeginterferon alfa-2b (tradename BESREMi®)

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the patient and ability for the patient to comply with the requirements of the study.
• Male or female patients ≥ 18 years old
• Patients diagnosed with ET according to the World Health Organization (WHO) 2016 criteria (with a bone marrow biopsy test result not more than 5 years old) who need cytoreductive treatment but are intolerant or refractory to, and/or ineligible for all cytoreductive treatments approved for the treatment of ET (i.e., HU, ANA, BUS, and PB1).
• Patients resistant/intolerant to HU must have documented resistance/intolerance as defined by modified ELN criteria (Barosi, et al. 2007), whereby at least one of the following criteria is met:
• Platelet count \>600 x 109/L at ≥2 g/day (or ≥2.5 g/day if patient body weight \>80 kg) or maximally tolerated dose if \<2 g/day or at maximum dose per local practice after at least 3 months of HU
• Platelet count \>400 x 109/L and WBC count \<2.5 x 109/L at any dose and any duration of HU
• Platelet count \>400 x 109/L and haemoglobin (Hb) \<10 g/dL at any dose and any duration of HU
• Presence of HU-related toxicities at any dose and any duration of therapy (e.g., leg ulcers, mucocutaneous manifestations, pneumonitis, or HU-related fever)
• Patients resistant/intolerant to ANA, BUS, or PB must meet at least one of the following criteria:
• Patient designated as non-responder according to the primary efficacy endpoint of this protocol (modified ELN criteria) after at least 3 months of treatment with the recommended dosing defined in SmPC or local practice
• Presence of treatment-related toxicities at any dose and any duration of therapy Patients ineligible for HU: with contraindication as defined by locally available HU SmPC or designated as such by investigator due to benefit-risk concerns (e.g., patients with toxic ranges of myelosuppression, teratogenic/leukaemogenic/carcinogenic concerns, male patients of reproductive, age not willing or unable to use an effective method of contraception). Patients ineligible for ANA: with contraindication as defined by locally available ANA SmPC or designated as such by investigator due to benefit-risk concerns (e.g., cardiovascular risk factors, including heart failure, QT prolongation, the risk for progression to myelofibrosis). Patient ineligible for BUS and PB (in countries where BUS or PB is available and approved for treatment of ET): with contraindication as defined by locally available BUS/PB SmPC or designated as such by investigator due to benefit-risk concerns (e.g., teratogenic/leukaemogenic/carcinogenic concerns, male patients of reproductive age not willing or unable to use an effective method of contraception).
• If a patient received prior cytoreductive treatment for ET, the washout period between the last dose of treatment and the first dose of the study drug must be at least 14 days, or longer. (If the washout period not completed at time of first patients screening, washout may be done after obtaining ICF during the 28-day screening phase).
• Interferon treatment-naïve
• Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), international normalised ratio ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at screening.
• Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales.

You may not qualify if:

• Any patient requiring a legally authorised representative
• Any hypersensitivity to IFN-α or to any of the drug excipients
• Pre-existing thyroid disease, if not in remission or not controlled with conventional treatment
• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt
• Severe cardiovascular disease (i.e., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction or pulmonary hypertension
• Patients with diabetes mellitus that cannot be effectively controlled by medicinal products
• History or presence of autoimmune disease (excluding well-controlled Hashimoto's disease)
• Immunosuppressed transplant recipients
• Concomitant treatment with telbivudine
• Decompensated cirrhosis of the liver (Child-Pugh B or C)
• End stage renal disease (GFR \<15 mL/min)
• Symptomatic splenomegaly (per the investigator's judgement)
• Patients 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:
• History of any malignancy within 5 years (except Stage 0 chronic lymphocytic leukaemia, basal cell, squamous cell, and superficial melanoma)
• Infections with systemic manifestations (e.g., bacterial, fungal, or human immunodeficiency virus \[HIV\], except hepatitis B \[HBV\] and/or hepatitis C \[HCV\], at screening)

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead

Study Sites (36)

University Hospital Graz, Department of Internal Medicine, Clinical Department of Hematology

Graz, Styria, 8036, Austria

Location

Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)

Innsbruck, Tyrol, 6020, Austria

Location

Ordensklinikum Linz GmbH Elisabethinen Hospital, Department of Internal Medicine I - Hemato-Oncology

Linz, Upper Austria, 4020, Austria

Location

Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology

Vienna, Austria

Location

University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology

Brno, 625 00, Czechia

Location

University Hospital Kralovske Vinohrady, Clinic of Internal Hematology

Prague, 10000, Czechia

Location

Centre Hospitalier Universitaire De Poitiers

Poitiers, Poitiers, 86000, France

Location

Saint-Louis Hospital, Department of Adult Hematology

Paris, 75010, France

Location

Bordeaux University Hospital, Haut-Leveque Hospital

Pessac, 33600, France

Location

University Hospital Aachen, Clinic of Oncology, Hematology and Stem Cell Transplantation (Medical Clinic IV)

Aachen, 52074, Germany

Location

University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology

Halle, 06120, Germany

Location

Hannover Medical School, Clinic for haematology, haemostaseology, oncology and stem cell transplantation

Hanover, 30625, Germany

Location

University Hospital Mannheim, Medical Clinic III, Hematology and Internistic Oncology

Mannheim, 68167, Germany

Location

Johannes Wesling Hospital Minden, Department of Oncology and Hematology

Minden, 32429, Germany

Location

University Hospital Ulm, Center for Internal Medicine, Clinic of Internal Medicine III, Department of Hematology, Oncology, Rheumatology, Infectious Diseases

Ulm, 89081, Germany

Location

General Hospital of Athens Alexandra, Therapeutic Clinic, Department of Therapeutics

Athens, 11528, Greece

Location

University General Hospital "Attikon"

Athens, PC 12462, Greece

Location

Semmelweis University, Department of Internal Medicine and Haematology, Division of Hematology

Budapest, H-1088, Hungary

Location

University of Debrecen Clinical Center, Clinic of Internal Medicine, Department of Hematology

Debrecen, 4032, Hungary

Location

Polyclinic S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Careggi University Hospital, Department of Hematology

Florence, 50134, Italy

Location

Umberto I Polyclinic of Rome

Rome, 00161, Italy

Location

University Polyclinic Foundation "Agostino Gemelli" - IRCCS, Service of Hematology

Rome, 00168, Italy

Location

University Hospital City of Health and Science of Turin - Hospital Molinette, Complex Structure of Hematology - U

Turin, 10126, Italy

Location

University Teaching Centre, Hematology and Transplantology Clinic

Gdansk, 80-952, Poland

Location

Pratia Oncology Katowice

Katowice, 40-519, Poland

Location

Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department

Krakow, 31-501, Poland

Location

Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz, Department of Hematooncology with Subdivision of Daytime Chemotherapy

Lodz, 93-513, Poland

Location

Onco Card Srl

Brasov, 500052, Romania

Location

"Prof. Dr. Ion Chiricuta" Institute of Oncology, Hematology Department

Cluj-Napoca, 400015, Romania

Location

Fundeni Clinical Institute, Center for Hematology and Bone Marrow Transplantation

Crişan, 022328, Romania

Location

Iasi Regional Institute of Oncology, Department of Hematology

Iași, 700483, Romania

Location

University Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Clinic of Barcelona, Department of Hematology

Barcelona, 08036, Spain

Location

University Hospital Ramon y Cajal, Hematology Service

Madrid, 28034, Spain

Location

Morales Meseguer University General Hospital

Murcia, 30008, Spain

Location

MeSH Terms

Conditions

Thrombocythemia, Essential; Thrombocytosis

Condition Hierarchy (Ancestors)

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

Study Design

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

Model Details: Open-label, single-arm, multicentre, descriptive study of ropeginterferon alfa-2b in essential thrombocythaemia patients

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 23, 2024
• Study Start: December 4, 2023
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 15, 2028
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2); DE (6); FR (3); RO (4); GR (2); IT (5); AU (4); HU (2); PL (4); ES (4)