Open-label, controlled, phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of INM004 in pediatric patients with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome

Abstract

Background Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study aimed to assess the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS. Methods Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other renal and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms. Results Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, trends toward a lower number of patients needing dialysis and dialysis for more than ten days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm. Conclusions INM004 showed an adequate safety profile. Efficacy trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a Phase 3 study of INM004 in pediatric patients with STEC-HUS.