Unknown Digestion, Kidneys & Other Organs NIHR-supported project Heart, Stroke & Blood

A global phase 3, randomised, double-blind and placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease

Funder NIHR (part of DHSC)
Recipient organisation NIHR Wellcome Trust Cambridge Clinical Research Facility
NIHR support Recorded as supported by this research centre
Period Feb 2025 — Ongoing

In plain English

AI plain-English summary

A daily pill called etavopivat is being tested against placebo in 408 adolescents and adults with sickle cell disease across the world. Sickle cell disease makes red blood cells stiff and sticky, causing them to block blood vessels. These blockages trigger sudden, severe pain episodes called vaso-occlusive crises, and over time they damage organs. Current treatments are limited. Etavopivat works by activating an enzyme inside red blood cells that helps them produce energy and bind oxygen more effectively, making the cells healthier and more flexible. If the trial shows etavopivat reduces the number of pain crises and slows organ damage, it could offer a new daily treatment option for people with sickle cell disease. The study also measures whether the drug improves exercise capacity and reduces fatigue—outcomes that directly affect daily life. Participants take either the drug or a placebo for the first 52 weeks, then all receive etavopivat for another 52 weeks. They attend 20 clinic visits for physical exams, walking tests, heart checks, and blood and urine tests, and use a smartphone app to log medication and pain episodes.

View original technical description
All organs in our body need oxygen to function optimally. Red blood cells are responsible for carrying oxygen from the lungs to all parts of the body. People with sickle cell disease produce unusually shaped red blood cells (sickle cells), that are stiff and sticky. This can cause blood vessels to get blocked causing pain, usually referred to as vaso-occlusive crises. This blockage of blood flow can also damage vital organs and tissue. Etavopivat is a small molecule that can activate a specific protein found in the red blood cells. This enzyme helps the red blood cells to produce energy and to bind oxygen, improving the health of red blood cells. We are doing this study to see how well etavopivat, the new medicine being tested, works in people living with sickle cell disease. We will evaluate if etavopivat reduces the patients' number of vaso-occlusive crisis and damage to organs. We will also evaluate whether etavopivat improves the patients' exercise capacity and reduces their fatigue.In the first 52 weeks participants will take etavopivat or placebo daily assigned by chance. In the second 52 weeks participants will take etavopivat daily. A total of 408 male and female adolescent and adults, older than 12 years with sickle cell disease across the world will participate in this study. To be able to be part of the study, participants should have between 1 and 15 vaso-occlusive crises (sickle cell pain crises) in the past year and have low red blood cell count (anaemia). The participants will be asked to come to 20 visits at the clinic. The participants will have physical examinations as well as other tests, including a walking exercise, heart checks and blood and urine tests. During specific clinic visits, participants will be asked to answer short questionnaires about their health and quality of life. Every day during the study, participants will use the Study App to register when they took the study medicine and register if they had any sickle cell pain.

Researchers

Martin Besser (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

An open-label, multi-centre, rollover study to characterise long-term safety and efficacy of Etavopivat in adults and children who have sickle cell disease or thalassemia and have completed a treatment period in an Etavopivat study
A research study looking at long-term treatment with etavopivat in people with sickle cell disease or thalassaemia (FLORAL)
A single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
A phase 2/3, double-blind, randomised, placebo-controlled, multicentre study to evaluate the efficacy and safety of Mitapivat in subjects with Sickle Cell Disease study
A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Sickle Cell Disease

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