Efficacy of INM004 in Children With STEC-HUS

A Phase III Study to Evaluate the Efficacy of INM004 (Shiga Antitoxin) in Pediatric Patients With Shiga Toxin-producing Escherichia Coli-associated Hemolytic Uremic Syndrome.

The objectives of this study are to evaluate the efficacy, safety, and pharmacokinetics of INM004 in pediatric patients with Hemolytic Uremic Syndrome associated to infection by Shiga toxin-producing Escherichia coli (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:

1. Age ≥ 9 months and < 18 years at the time of randomization.

2. In addition, only for subjects < 1 year and ≥ 15 years, confirmation of STEC infection determined by:

   1. Detection of generic Stx, Stx1, Stx2, or Stx1/Stx2 in stools by enzyme immunoassay (EIA); or
   2. Detection of stx, stx1, stx2, or stx1/stx2 genes in stools by Polymerase Chain Reaction (PCR); or
   3. Detection of specific anti-polysaccharide (IgM) antibodies in serum; or
   4. Fecal culture positive for E. coli O157 confirmed by serogroup-specific seroagglutination.

3. Hospitalization at the participating institution.

4. History of onset of diarrhea within 10 days prior to STEC-HUS diagnosis at the participating institution.

5. Diagnosis of STEC-HUS defined as a subject with signs of renal damage, hemolysis, and platelet consumption:

   1. 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.

   2. Presence of hemolysis documented by:

      • LDH levels above the ULN for age, and/or
      • Presence of schistocytes in peripheral blood smear.

   3. 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.

6. 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.

7. Subjects who have already had menarche must have a negative pregnancy test.

Exclusion Criteria:

1. Start of dialysis within 48 hours prior to admission to the participating institution.

2. More than 24 hours from diagnosis of STEC-HUS at the participating institution up to randomization.

3. History of chronic/recurrent hemolytic anemia, thrombocytopenia, or CKD.

4. Personal and/or family history of atypical HUS.

5. Suspected HUS secondary to infectious processes other than gastrointestinal (e.g., Streptococcus pneumoniae, HIV).

6. Suspected HUS secondary to other etiologies (e.g., drug-associated HUS, neoplasms, bone marrow or solid organ transplantation, autoimmune disorders).

7. 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.

8. 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.

9. Pregnant or breastfeeding woman.

10. Impossibility of hospitalization in the participating institution.

11. Concurrent participation in another clinical trial or having participated in a clinical trial in the last 3 months.

12. Severe malnutrition. Defined when the weight is three standard deviations below the median, according to height, age and sex as per WHO guidelines.

13. 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).