Clinical Trials in Graft-Versus-Host Disease: Changes in Study Characteristics, Investigated Drugs, and Endpoints Over Time

BACKGROUND: Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). Mapping the trial landscape is essential to identify innovation barriers and optimize future study designs and trial conduct. OBJECTIVES: This analysis characterized GvHD treatment trials registered on ClinicalTrials.gov to evaluate design features and results reporting trends. RESULTS: Following screening of 1713 identified records, 384 trials met the specified inclusion criteria. Phase distribution was 15.9% phase 1, 38.8% phase 2, and 11.2% phase 3 studies. Single-group (61.1%) and parallel (31.3%) designs predominated, with sponsors being primarily academic (60.4%) or industry (30.7%). Regarding study status, 37.0% were completed, 22.9% prematurely halted, and 24.7% ongoing (15.4% unknown). For completed studies, the median number of participants was 30 and the median duration to reach the primary outcome was 3.13 years. Chronic GvHD was studied slightly more often (47.9%) than acute GvHD (43.5%), with significant differences in terms of study phases, recruitment status, duration, sponsor, and organ involvement. The most frequently studied treatments were corticosteroids (n = 64), mesenchymal stromal cells (n = 52), ruxolitinib (n = 31), extracorporeal photopheresis (n = 26), fecal microbiota transplantation (n = 17), rituximab (n = 15), and belumosudil (n = 13). The majority of trials (55.2%) investigated steroid-refractory GvHD or later-line treatment. Over the last decade, a significant shift toward industry sponsorship (13.4% to 38.9%, p < .001), multicenter designs, and targeted therapies was observed. Response was the predominant (60.1%) co-/primary endpoint of GvHD studies, followed by safety (28.2%), whereas patient-reported outcomes played a minor role (6.4%). Time to result reporting differed significantly based on trial phase and design. CONCLUSIONS: While the trial landscape is evolving toward multinational collaborations and biology-based agents, the high rate of premature termination remains a substantial barrier to progress. Optimizing the study design, including regulatory advice, recruitment, and logistics, is critical to improve long-term outcomes in transplant recipients.