BACKGROUND: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.
AIM: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months post-transplantation. The secondary objective included the assessment of safety up to 12 months post-infusion, and of preliminary efficacy.
METHODS: Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with three doses of HepaStem. Clinical status, portal-vein hemodynamics, morphology of the liver, de novo detection of circulating anti-human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events (SAEs) to infusion were evaluated by using an intent-to-treat analysis.
RESULTS: The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the SAEs, of which 38% occurred within one month post-infusion. There was a trend of higher events in UCD as compared to CN patients. Segmental left portal vein thrombosis occurred in one patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age and underlying diseases.
CONCLUSIONS: This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.