| Protocol No: | ECCT/25/08/05 | Date of Protocol: | 03-05-2024 |
| Study Title: |
An open-label, multi-centre, rollover study to characterise long-term safety and efficacy of etavopivat in adults, adolescents and children who have sickle cell disease or thalassaemia and have completed a treatment period in an etavopivat study.
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An open-label, multi-centre, rollover study to characterise long-term safety and efficacy of etavopivat in adults, adolescents and children who have sickle cell disease or thalassaemia and have completed a treatment period in an etavopivat study
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| Study Objectives: |
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| 1 | Primary Objective: To investigate long-term safety of etavopivat in adults, adolescents and children with SCD, SCDTD, TDT or NTDT transferring from the Hibiscus, HibiscusKids, Hibiscus3 and Gladiolus studies. Secondary objectives To investigate long-term clinicalefficacy measures of etavopivat treatment in adults, adolescents and children with SCD transferring from the Hibiscus, HibiscusKids, Hibiscus3 and Gladiolus studies. To evaluate the effects of etavopivat on hospitalisations in adults, adolescents and children with SCD transferring from the Hibiscus, HibiscusKids, Hibiscus3 and Gladiolus studies. To investigate long-term clinical efficacy measures of etavopivat treatment in adults and adolescents with NTDT transferring from the Gladiolus study. To investigate long-term clinical efficacy measures of etavopivat treatment in adults and adolescents with TDT or SCDTD, transferring from the Gladiolus study. |
| Laymans Summary: |
A research study looking at long-term treatment with etavopivat in people with sickle cell disease or thalassaemia.
The purpose of this rollover study is to investigate the long-term safety of etavopivat in participants 11 months of age and older with SCD or thalassaemia who have completed a treatment period in previous etavopivat studies.
Long-term clinical efficacy measures of etavopivat treatment will also be assessed. This study will also ensure that participants who are benefiting from etavopivat treatment have prolonged access to the drug in the time before it is commercially available in their country.
Etavopivat is an orally bioavailable, small-molecule activator of pyruvate kinase red blood cell (PKR) isozyme. The investigational medicinal product (IMP) is being developed for the treatment of inherited haemoglobinopathies, such as Sickle cell disease (SCD) and thalassemia.
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| 1 | People with sickle cell disease produce unusually shaped red blood cells (sickle cells). These are stiff and sticky and can cause blood vessels to get blocked causing pain, referred to as vaso-occlusive crises (sickle cell pain crises). This can also damage vital organs and tissue. People with thalassaemia do not make enough haemoglobin or make abnormal haemoglobin, which can cause red blood cells to be destroyed, and cause anaemia. People with thalassaemia who need regular blood transfusions to survive are said to have transfusion-dependent thalassaemia while those that do not are said to have non-transfusion-dependent thalassaemia. Etavopivat is a small molecule that activates a specific protein found in red blood cells. This protein helps red blood cells to bind oxygen and to produce energy, which improves red blood cell health. These effects may help reduce the symptoms of people with sickle cell disease and thalassaemia. This study will help us understand how safe etavopivat is when you take it for a longer time, and how well it works in people with the inherited blood disorders sickle cell disease or thalassaemia |
| Abstract of Study: |
This is an interventional, multi-national, multi-centre, open-label, phase 3b study in adults (participants ≥ 18 years old), adolescents (participants ≥ 12 to < 18 years old) and children(participants ≥ 11 months to < 12 years old) with sickle cell disease (SCD), with SCD who have been on chronic transfusions to prevent primary stroke or recurrence of stroke (SCDTD), non-transfusion-dependent thalassaemia (NTDT) or transfusion-dependent thalassaemia (TDT).
The purpose of this rollover study is to investigate the long-term safety of etavopivat in participants 11 months of age and older with SCD or thalassaemia who have
completed a treatment period in previous etavopivat studies. Long-term clinical efficacy measures of etavopivat treatment will also be assessed.
Etavopivat is an orally bioavailable, selective activator of erythrocyte pyruvate kinase (PKR), currently under development in clinical studies as a potential treatment for inherited haemoglobinopathies, including SCD and thalassemia.
Approximately 325 participants are planned to be enrolled in the study in about 120 sites worldwide. All participants will receive etavopivat. Participants ≥ 12 years old will receive an oral dose of 400 mg QD administered as 2 × 200 mg tablets. Participants < 12 years old will receive an age- and weight-adjusted dose (400 mg QD equivalent 1.0dose) administered as granules.
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| 1 |
This is an interventional, multi-national, multi-centre, open-label, phase 3b study in adults
(participants ≥18 years old), adolescents (participants ≥12 to <18 years old) and children (participants ≥2 to <12 years old) with sickle cell disease (SCD), with SCD who have been on chronic transfusions to prevent primary stroke or recurrence of stroke (SCDTD),
non-transfusion-dependent thalassaemia (NTDT) or transfusion-dependent thalassaemia (TDT).The purpose of this rollover study is to investigate the long-term safety of etavopivat in participants
from 2 years of age and older with SCD or thalassaemia who have completed a treatment period in previous etavopivat studies (parent studies, see Section 4.1). Long-term clinical efficacy measures
of etavopivat treatment will also be assessed. This study will also ensure that participants who are benefiting from etavopivat treatment have prolonged access to the drug in the time before it is commercially available in the country.
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