The Congenital Athymia Patient Registry: An Observational Cohort Study to Evaluate the Real-World Efficacy and Safety of Allogeneic Processed Thymus Tissue-agdc

Abstract

Congenital athymia is an ultra-rare condition characterized by the absence of a functioning thymus and severe immunodeficiency. Allogeneic processed thymus tissue-agdc (RETHYMIC®) is an approved treatment for immune reconstitution in pediatric patients with congenital athymia. The Congenital Athymia Patient Registry is an observational cohort study designed to evaluate immune reconstitution after administration of allogeneic processed thymus tissue-agdc, determine how treatment impacts long-term survival, and record incidence of adverse events of special interest (AESIs) and hospitalizations. Results from this registry will provide additional information for healthcare providers who are treating patients with congenital athymia. The primary objectives are to evaluate survival at 1 year and 2 years posttreatment and to characterize immune reconstitution over time after treatment. The secondary objective is to evaluate incidence and timing of AESIs within 2 years posttreatment. An exploratory objective is to evaluate overall survival beyond 2 years posttreatment. Eligibility criteria include a confirmed congenital athymia diagnosis, treatment with allogeneic processed thymus tissue-agdc, and written informed consent. Data will be abstracted from medical records at baseline (pre implantation), every 3 months during the first year after allogeneic processed thymus tissue agdc administration, every 6 months during the second year, and each year thereafter. Survival will be assessed by vital status at 12 months, 24 months, and beyond 2 years after treatment with allogeneic processed thymus tissue-agdc. Immune reconstitution will be evaluated by flow cytometry assessing total and naïve CD3, CD4, and CD8 T-cell counts over time. Hospitalizations, AESIs, spontaneous adverse events, immunosuppressive medication use, immunoglobulin replacement therapy, and vaccination administration will be recorded over time. The target sample size is 75 patients over a 3-year enrollment period; all patients will receive allogeneic processed thymus tissue-agdc at a single site. Enrollment began in 2022 and 6 patients have been enrolled as of September 2022. The study will end when all patients have achieved at least 2 years of follow-up, died, or withdrawn consent. Data from this ongoing registry will provide real-world evidence to supplement safety and efficacy results from clinical trials of allogeneic processed thymus tissue-agdc and may inform future guidelines for patient care after administration.