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Clinical Trial
. 2025 Jun;40(6):1983-1995.
doi: 10.1007/s00467-024-06583-3. Epub 2024 Nov 12.

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

Alicia Fayad #  1 , Iliana Principi #  2 , Alejandro Balestracci  3 , Laura Alconcher  4 , Paula Coccia  5 , Marta Adragna  6 , Oscar Amoreo  7 , María Carolina Bettendorff  8 , María Valeria Blumetti  9 , Pablo Bonany  10 , María Laura Flores Tonfi  11 , Luis Flynn  12 , Lidia Ghezzi  5 , Jorge Montero  13 , Flavia Ramírez  14 , Claudia Seminara  15 , Ángela Suarez  16 , Ana Paula Spizzirri  16 , Marta Rivas  17 , Mariana Pichel  17 , Vanesa Zylberman  17 , Linus Spatz  17 , Carolina Massa  17 , Marina Valerio  17 , Santiago Sanguineti  17 , Mariana Colonna  17 , Ian Roubicek  17 , Fernando Goldbaum  18   19 ; INM004 Study Group
Affiliations
Clinical Trial

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

Alicia Fayad et al. Pediatr Nephrol. 2025 Jun.

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 the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing 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 kidney 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, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10 days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm.

Conclusions: INM004 showed an adequate safety profile. Efficacy non-statistically significant 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.

Keywords: Acute kidney injury; Clinical trial, Phase 2; Hemolytic uremic syndrome; Passive immunotherapy.

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Conflict of interest statement

Declarations. Ethics approval: This trial was performed following the principles of the Declaration of Helsinki and Good Clinical Practice. The protocol was approved by the local Ethics Committees of each of the participating centers and the Argentine National Food and Drug Regulatory Agency (ANMAT) after approval by the Ethics Committee accredited by the corresponding Health Authority within the jurisdiction (Disposition Number: DI-2022–7068-APN-ANMAT#MS). Conflict of interest: AF, IP, AB, LA, PC, MA, OA, MCB, MVB, PB, MLFT, LF, LG, JM, FR, CS, AS, and APS declare reimbursement for conduction of clinical trial as investigator of the study. MR, MP, VZ, LS, CM, MV, SS, MC, IR, and FG report personal fees from Inmunova S.A.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Study design and procedures. a Study design. b Visit schedule and procedures. STEC-HUS, Escherichia coli-associated hemolytic uremic syndrome; Dx, diagnosis; D, day; PK, pharmacokinetics; AEs, adverse events
Fig. 2
Fig. 2
Study secondary and exploratory outcomes. TMA, thrombotic microangiopathy; eGFR, estimated glomerular filtration rate; sCr, serum creatinine; LDH, lactate dehydrogenase; LLN, lower limit of normal; a, eGFR lower limit of normal (LLN) for each subject was estimated with the Bedside Schwartz equation [36], using the serum creatinine upper limit of normal (ULN) for age and sex (eGFRLLN (ml/min/1.73 m2) = (0.413 × height in cm)/CreatinineULN (mg/dL) for age and sex) reported by Chuang et al. (2021) [37]
Fig. 3
Fig. 3
Participant disposition. FAS, full analysis set; MP, matched population; SP, safety population. *Some subjects were counted more than once because they did not meet some inclusion criteria and also met some exclusion criteria
Fig. 4
Fig. 4
Laboratory parameters of the thrombotic microangiopathy during the entire follow-up period—matched population. a Creatinine; b eGFR, estimated glomerular filtration rate; c hemoglobin; d platelets.
Fig. 5
Fig. 5
Kaplan–Meier cumulative incidence of glomerular filtration rate recovery during the follow-up period. GFR, glomerular filtration rate; LLN, lower limit of normal
See this image and copyright information in PMC

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