| Protocol No: | ECCT/26/06/02 | Date of Protocol: | 17-12-2025 |
| Status: | Approved | Date Approved: | 23-10-2026 |
| Study Title: |
A global phase 3 Randomised, Double-blind and Placebo-controlled Study Evaluating the Efficacy and Safety of etavopivat in children with Sickle Cell Disease.
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| Study Objectives: | Primary Objectives To demonstrate superiority in reducing the VOC rate with etavopivat treatment compared to placebo in children with SCD Secondary Objectives 1.To compare the time to first VOC event between etavopivat treatment and placebo in children with SCD 2. To compare change in fatigue scores between etavopivat treatment and placebo in children with SCD 3. To compare the Hb response rate between etavopivat treatment and placebo in children with SCD 4. To compare the effect on haemolysis biomarkers between etavopivat treatment and placebo in children with SCD 5. To compare the safety and tolerability of etavopivat treatment versus placebo in children with SCD during the double-blind treatment period 6. To evaluate the effects of etavopivat versus placebo on hospitalisations and absenteeism
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| Laymans Summary: | Background SCD is caused by the inheritance of a mutated form of haemoglobin (Hb) called sickle Hb (HbS). The disease is characterised by a polymerisation of deoxygenated HbS in the red blood cells (RBCs). Polymerised HbS forms rigid aggregates that alter membrane elasticity and results in a sickle-shaped deformation of the cell. Sickled RBCs tend to be fragile, whereby the mechanical trauma of circulation causes haemolysis and chronic anaemia. Sickled cells can aggregate in capillaries, blocking blood flow and triggering VOCs, which is a hallmark of SCD. The acute and painful events are consequences of tissue ischaemia leading to infarction and oedema. Haemolysis of sickled RBCs is associated with inflammatory changes, endothelial and vascular damage and organ disorders such as stroke, pulmonary hypertensions, and leg ulcers. Collectively, these factors contribute to the significant morbidity and increased mortality associated with SCD. Etavopivat is an allosteric activator of the pyruvate kinase red blood cell isozyme (PKR), a key enzyme in glycolysis. In SCD, PKR activation reduces 2,3-diphosphoglycerate (2,3-DPG) levels and increases adenosine triphosphate (ATP) production. Reduction of 2,3-DPG improves Hb oxygen (O2) affinity, averting HbS polymerisation and subsequent sickling. The increase in ATP production helps preserve RBC membrane integrity and deformability, improving RBC survival. These disease-modifying effects are expected to lead to a reduction in VOC events and improve anaemia. Synopsis This is an interventional, multi-national, multi-centre, randomised (1:1), double-blind, placebo-controlled, study in participants aged 2 to < 12 years of age with sickle cell disease (SCD), who had 2 to 15 vaso-occlusive crises (VOCs) in the year prior to screening. Rationale: This study aims to evaluate the efficacy of etavopivat (compared to placebo) on annualised VOC rates in children. In addition, this study aims to evaluate the safety of etavopivat and explore additional benefits of etavopivat compared to placebo. The purpose of the study is to provide scientific evidence supporting the benefit-risk profile in paediatric participants aged 2 to younger than 12 years. A single-arm phase 2 study in this age group is currently ongoing 4202-HEM-202 (HibiscusKids) and the present study will further strengthen paediatric data for etavopivat.
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| Abstract of Study: | Introduction Sickle cell disease (SCD) and thalassaemia, both inherited haemoglobinopathies, are among the most common monogenic diseases worldwide and among the most common causes of chronic haemolytic anaemia.1 In 2007, the World Health Organization estimated that 5.2% of the population worldwide carries a haemoglobinopathy gene variant, classifying the disease group as a growing global health problem.2 People diagnosed with haemoglobinopathies often have a poor quality of life and a life expectancy reduced by 20 to 30 years.3 The lack of effective treatment strategies for patients with haemoglobinopathies reflects a critical unmet medical need. Etavopivat is currently under development in clinical studies as a potential treatment for SCD and other inherited haemoglobinopathies, such as thalassaemia. Study rationale The objective of this study is to evaluate efficacy and safety of etavopivat (compared to placebo) supporting the benefit-risk profile in children younger than 12 years of age with SCD. Etavopivat (or placebo) will be added to standard of care with the primary endpoint being the reduction in the annualised rate of vaso-occlusive crises (VOCs) from baseline to week 52 in children with SCD. As a pharmaceutical company, Novo Nordisk has a legitimate interest in conducting research to learn how the medicines and devices we develop work and learn more about how to prevent and/or treat serious chronic diseases and related conditions. As part of conducting research, Novo Nordisk also has a legitimate interest to communicate the results of our research, and interact with competent authorities. Novo Nordisk may also share data with external researchers who are not part of this study for research purposes, to find out more about etavopivat, SCD or related conditions and to help improve medical care and scientific understanding. |