Phase 2a trial of dazodalibep plus belatacept shows 25% acute rejection rate in kidney transplant patients

This phase 2a, open-label, single-arm trial evaluated the efficacy and safety of dual costimulation blockade with dazodalibep (CD154-specific) and belatacept (CD80/86-specific) as sole maintenance therapy for rejection prophylaxis. The study enrolled 23 adults undergoing their first, nonidentical kidney transplant from deceased or living donors. The primary endpoint was a composite of efficacy failure (treated biopsy-proven acute rejection of grade 1A or higher, graft loss, or death) at week 24, with follow-up through week 48.

Regarding efficacy, the prespecified primary composite endpoint was not met among patients who completed the study. Of 20 evaluable patients, 5 (25%) experienced treated biopsy-proven acute rejection of grade 1A or higher. No antibody-mediated rejection events were reported. Kidney function was described as similar between patients who did and did not experience rejection through 24 weeks, though specific numerical data were not provided.

Safety and tolerability data indicated the regimen was generally safe and well tolerated. Most patients (22 of 23, 96%) experienced at least 1 treatment-emergent adverse event. Only 13 of the 23 enrolled patients (56.5%) completed the study, with 10 patients discontinuing. Key limitations include the open-label, single-arm design, the small sample size (n=23), and the high rate of study non-completion, which limits interpretability.

Given the preliminary nature of this phase 2a evidence, the lack of a comparator group, and the failure to meet the primary efficacy endpoint, these findings should be interpreted with caution. The regimen's role in clinical practice cannot be determined from this single-arm study.