Sickle Cell Disease Clinical Trials in the UK (2026)
26 May 202611 min readTrialConnect Research Team
Sickle cell disease (SCD) affects over 17,000 people in the UK, making it the most common inherited blood disorder in the country. The UK has been at the forefront of SCD research, and in 2023 the MHRA became the first regulator in the world to approve Casgevy (CRISPR-based gene therapy) for SCD. Here is what is actively recruiting across the UK trial landscape.
The UK has a comprehensive network of sickle cell centres, and the NHS Sickle Cell and Thalassaemia Screening Programme ensures universal newborn screening. The National Haemoglobinopathy Panel coordinates clinical care, and the British Society for Haematology actively supports SCD research.
There are currently over 50 actively recruiting sickle cell trials in the UK. The therapeutic landscape has transformed: from hydroxyurea as the only disease-modifying therapy a decade ago to CRISPR gene editing, gene addition therapy, and multiple novel agents targeting every aspect of the disease.
Types of SCD Trials
Gene Therapy & Editing
CRISPR-Cas9 (Casgevy), lentiviral gene addition (LentiGlobin), and base editing therapies offering potential one-time cures.
The UK is a world leader in SCD gene therapy, driven by MHRA's early approval and the NHS's commitment to funding:
Casgevy (exagamglogene autotemcel) — CRISPR-Cas9 editing of BCL11A in haematopoietic stem cells to boost foetal haemoglobin (HbF). UK follow-up trials are tracking long-term durability, the need for boost transfusions, and outcomes in older patients
LentiGlobin (lovotibeglogene autotemcel) — lentiviral gene addition of a modified beta-globin gene, approved in the US and in UK Phase 3 follow-up studies
Next-generation CRISPR approaches — base editing and prime editing targeting the beta-globin promoter and BCL11A binding sites, potentially reducing transplantation conditioning intensity
In vivo gene editing — very early-phase UK trials exploring whether CRISPR editing can be delivered directly to haematopoietic stem cells without ex vivo manipulation and chemotherapy conditioning
Disease-Modifying Therapies
Beyond hydroxyurea and gene therapy, several new pharmacological approaches are in trials:
Mitapivat — a pyruvate kinase activator that increases red cell ATP and decreases 2,3-DPG, reducing sickling propensity. In UK Phase 3 trials following encouraging Phase 2 data
Voxelotor (GBT440/GBT601) — haemoglobin S polymerisation inhibitor that increases haemoglobin-oxygen affinity. UK post-marketing studies exploring long-term outcomes, including effects on haemolysis and pulmonary hypertension
HbF induction by novel mechanisms — pomalidomide analogues, LSD1 inhibitors, and oral decitabine-based approaches to pharmacologically boost foetal haemoglobin
Anti-inflammatory agents — statins, zileuton (5-lipoxygenase inhibitor), and other anti-inflammatory drugs targeting chronic SCD inflammation beyond acute crises
Pain Management and VOC Prevention
Vaso-occlusive crises are the most common reason for SCD hospitalisation:
Anti-P-selectin antibodies — crizanlizumab (Adakveo) and next-generation anti-adhesion molecules in UK trials following real-world evidence of efficacy
Nitric oxide modulation — inhaled NO, L-arginine, and sildenafil trials for acute VOC treatment, pulmonary hypertension, and chronic haemolysis-related complications
Novel analgesic approaches — trials of ketamine infusion protocols for acute VOC, low-dose naltrexone for chronic pain, and cannabinoid-based therapies for sickle cell pain
Pacing and prevention programmes — RCTs of hydration and warming protocols, hydroxyurea dose adjustments, and proactive crisis prevention strategies
Paediatric Sickle Cell Research
Children with SCD have distinct needs, and UK centres are active in paediatric-specific trials:
Stroke prevention in children — the UK STOP extension studies using transcranial Doppler ultrasound screening, with trials of intensified transfusion vs. hydroxyurea for abnormal TCD velocities
Early gene therapy — trials evaluating whether gene therapy (Casgevy, LentiGlobin) at younger ages (3–12 years) prevents irreversible organ damage before it occurs
Cognitive outcomes in paediatric SCD — longitudinal trials tracking neurocognitive development in children with SCD and evaluating early intervention strategies
Acute chest syndrome management — trials of early intervention strategies including bronchodilators, inhaled steroids, and antibiotic protocols
Haploidentical transplant in children — reduced-intensity conditioning protocols for children lacking a matched sibling donor, using T-cell replete haploidentical grafts
Stem Cell Transplant
Allogeneic haematopoietic stem cell transplant remains the only established curative option beyond gene therapy. UK trials are expanding access:
Reduced-intensity conditioning — UK multi-centre trials of alemtuzumab-based and fludarabine/melphalan-based RIC protocols to reduce transplant-related mortality
Haploidentical transplant — using half-matched family donors with post-transplant cyclophosphamide, expanding donor availability to virtually all patients
Matched unrelated donor transplant — optimising donor selection and conditioning for patients without a matched sibling donor, using UK blood donor registries
Gene-modified autologous transplant — bridge trials between standard transplant and gene therapy, using the same conditioning regimens but with gene-corrected autologous stem cells
Mixed chimerism management — trials determining the level of donor chimerism needed for clinical cure and strategies to maintain stable mixed chimerism
Who Can Participate?
Eligibility varies by trial type but commonly includes:
Gene therapy trials — confirmed diagnosis of SCD (HbSS, HbSβ0-thalassaemia, or other severe genotype), age 12–45 (some extend to 60), history of ≥2–4 vaso-occlusive crises per year, adequate stem cell mobilisation potential, no active organ failure or significant iron overload
Disease-modifying therapy trials — may include milder genotypes (HbSC, HbSβ+), require documented baseline haemoglobin and crisis rate, and may allow concurrent hydroxyurea
Pain trials — require documented VOC history, may specifically target patients with frequent crises (≥2 per year) or chronic pain
Stem cell transplant trials — severe SCD with end-organ damage (stroke, acute chest syndrome, pulmonary hypertension), adequate organ function, available donor, age typically 2–45
General exclusions — for gene therapy/transplant: active infection, significant organ dysfunction (liver cirrhosis, advanced renal disease), active malignancy, and inability to undergo stem cell mobilisation
💡 Tip: Prepare Your Crisis History
Trial teams will need your crisis history for the past 1–2 years — how many VOC episodes requiring hospital attendance, what treatments were needed (IV fluids, opioids, transfusion), any acute chest syndrome episodes, stroke history, and current treatments (hydroxyurea dose, transfusions, crizanlizumab). Your haematology team can provide a comprehensive summary. For gene therapy trials, additional tests include iron studies, liver MRI (FerriScan), and stem cell mobilisation assessment.
UK Sickle Cell Trial Locations
Major UK centres running SCD trials include:
London — King's College Hospital (one of the UK's largest SCD centres), St George's Hospital, Imperial College, Guy's and St Thomas', University College London Hospitals
Manchester — Manchester Royal Infirmary, Central Manchester University Hospitals
Birmingham — City Hospital (Sandwell and West Birmingham), Queen Elizabeth Hospital, Birmingham Children's Hospital
Bristol — Bristol Royal Hospital for Children, University Hospitals Bristol
Sheffield — Royal Hallamshire Hospital, Sheffield Children's Hospital
Leicester — Leicester Royal Infirmary, University of Leicester
Nottingham — Queen's Medical Centre, Nottingham University Hospitals
Oxford — Oxford University Hospitals, Churchill Hospital
How to Find Your Match
Use our Smart Matcher to find SCD trials tailored to your genotype, crisis frequency, organ complications, and treatment goals. Whether you are exploring CRISPR gene therapy as a potential cure, looking for better pain management, or seeking to prevent complications, we can match you to actively recruiting studies.