Efficacy of INM004 in Children With STEC-HUS

The primary objective will be to evaluate the efficacy of INM004, added to the standard of care, as a treatment for STEC-HUS in the amelioration of renal function.

Secondary objectives

• To evaluate the efficacy of INM004 in the reduction of mortality.
• To evaluate the efficacy of INM004 in the prevention and reduction of extrarenal complications.
• To evaluate the efficacy of INM004 in the improvement of TMA laboratory parameters.
• To evaluate the efficacy of INM004 in the reduction of hospital stay days.
• To evaluate the safety of INM004
• To evaluate the pharmacokinetics of INM004
• To evaluate the kinetics of Stx

Inclusion criteria

• Age ≥ 9 months and < 18 years at the time of randomization.
• In addition, only for subjects < 1 year and ≥ 15 years, confirmation of STEC infection determined by:

• Detection of generic Stx, Stx1, Stx2, or Stx1/Stx2 in stools by enzyme immunoassay (EIA); or
• Detection of stx, stx1, stx2, or stx1/stx2 genes in stools by Polymerase Chain Reaction (PCR); or
• Detection of specific anti-polysaccharide (IgM) antibodies in serum; or
• Fecal culture positive for E. coli O157 confirmed by serogroup-specific seroagglutination.
• Hospitalization at the participating institution.
• History of onset of diarrhea within 10 days prior to STEC-HUS diagnosis at the participating institution.
• Diagnosis of STEC-HUS defined as a subject with signs of renal damage, hemolysis, and platelet consumption:

• Signs of renal damage defined as:

• Serum creatinine value above the ULN for age and sex, and GFR below the LLN for age, sex, and height.
• Presence of hemolysis documented by:

• LDH levels above the ULN for age, and/or
• Presence of schistocytes in peripheral blood smear.
• Platelet consumption according to any of the following laboratory criteria:

• Peripheral blood platelet count < 150 × 103/μL, and/or
• A ≥50% decrease in peripheral blood platelet count compared to a sample collected within the previous 24 hours.
• Informed consent form signed and dated by the subject or, the legal guardian(s), with the subject's assent as appropriate based on age and regulatory guidelines in the region.
• Subjects who have already had menarche must have a negative pregnancy test.

Exclusion criteria

• Start of dialysis within 48 hours prior to admission to the participating institution.
• More than 24 hours from diagnosis of STEC-HUS at the participating institution up to randomization.
• History of chronic/recurrent hemolytic anemia, thrombocytopenia, or CKD.
• Personal and/or family history of atypical HUS.
• Suspected HUS secondary to infectious processes other than gastrointestinal (e.g., Streptococcus pneumoniae, HIV).
• Suspected HUS secondary to other etiologies (e.g., drug-associated HUS, neoplasms, bone marrow or solid organ transplantation, autoimmune disorders).
• Any other acute or chronic medical condition that, in the opinion of the investigator, may interfere with the evaluation of the efficacy and/or safety of the study medication.
• History of: a) anaphylaxis of any kind; b) prior administration of equine serum (e.g., antivenom, anti-arachnid serum, anti-SARS-CoV-2 serum, etc.) or an allergic reaction from contact or exposure to horses.
• Pregnant or breastfeeding woman.
• Impossibility of hospitalization in the participating institution.
• Concurrent participation in another clinical trial or having participated in a clinical trial in the last 3 months.
• Severe malnutrition. Defined when the weight is three standard deviations below the median, according to height, age and sex as per WHO guidelines.
• Medical conditions that may affect kidney function or cause/enhance neurological symptoms or signs:

• Congenital or acquired anomalies that may affect functioning renal mass.
• Epilepsy or structural abnormalities of the brain that may increase the risk of seizures.
• Trisomy 21.
• Prematurity (born before 28 weeks gestation).
• Other (according to investigator criteria).