Phase 2/3 Study to Evaluate PK, Safety & Efficacy of INM004 in STEC Positive Pediatric Patients for Prevention of HUS
Bloody Diarrhea, STEC, Unspecified, Hemolytic-Uremic Syndrome
About this trial
This is an interventional prevention trial for Bloody Diarrhea
Eligibility Criteria
Inclusion Criteria:
- Age of ≥ 1 to < 10 y.
- Signed informed consent from the parent(s)/legal guardian with assent from the subject as appropriate by age and regulatory guidance.
- Bloody diarrhea based upon history or presentation (by visual inspection).
Detection of Stx2 in stool based on enzyme immunoassay (EIA) and/or stx2 based on PCR before randomization.
NOTE: The basis for accepting a positive test for stx2 by EIA is based on taking as valid the results yielded from an EIA whose sensitivity and specificity are greater than 98.7% and 100%, respectively (according to the description in the insert) as per recommendation given by the NRL. The Sponsor will select the investigational sites that have in their laboratory such EIA test used in the STEC diagnostic routine algorithm. (Appendix 6).
- For children between 1 to 5 years old: weight for length/height between percentiles 3 (< 2 z score) and 97 (> 2 z score) corresponding to age (according to the reference tables "WHO Child Growth Standards".
- For children ≥ 5 years: Body mass index (BMI) between percentiles 3 (<2 z score) and 97 (> 2 z score) corresponding to age (according to the reference tables "WHO Child Standards, Appendix 4)
Exclusion Criteria:
Any laboratory findings compatible with the development of HUS:
- Microangiopathic hemolytic anemia defined as LDH above the ULN for age with the finding of schistocytes on peripheral smear and a negative Coomb's test, and/or
- Thrombocytopenia: platelet count < 150 × 103/μL, and/or
- Renal failure: serum creatinine > ULN adjusted for age and gender criteria despite correction of hypovolemia, and/or hematuria, and/or proteinuria (Table 7.1)11 NOTE: Laboratory results must be obtained within 24 h before the 1st study drug administration; there must be no clinical signs and symptoms of HUS at the time laboratory assessments are obtained. If there is any change in clinical presentation in the 24 h before the 1st study drug administration, laboratory assessments are to be repeated and results reviewed before study drug administration.
NOTE: Laboratory and physical examination results must indicate normal hydration before the 1st study drug administration.
- A history of chronic/recurrent hemolytic anemia, thrombocytopenia, or chronic renal failure.
- A family history of aHUS.
- Anuria or oliguria after hypovolemia is corrected.
- Evidence of clinically significant chronic active disease not medically controlled.
- History of anaphylaxis, prior administration of equine serum (eg, antitetanus serum or anti-ophidic serum, or anti-arachnid toxin serum), or allergic reaction to contact with, or exposure to, horses.
Family relation or work relation with a member of the personnel of the research group.
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Sites / Locations
- Hospital Penna
- Hospital Sor Maria Ludovica
- Hospital Lucio Molas
- Hospital Castro Rendon
- Hospital Elizalde
- Hospital Italiano de Buenos Aires
- Hospital Orlando Alassia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Active Comparator
Active Comparator
Placebo Comparator
Active Comparator
Active Comparator
Stage 1 - high treatment arm
Stage 1 - Low treatment arm
Stage 1 - Placebo arm
Stage 2 - Selected active treatment arm
Stage 2 - Placebo arm
Subjects will receive a 1st intravenous dose of 4 mg/kg INM004 (Anti-Stx hyperimmune equine immunoglobulin F[ab']2 fragments) and a 2nd intravenous dose of 4 mg/kg of INM004. Each dose will be separated by 24 h (± 2 h).
Subjects will receive a 1st intravenous dose of 4 mg/kg INM004 (Anti-Stx hyperimmune equine immunoglobulin F[ab']2 fragments) and a 2nd intravenous dose of Placebo. Each dose will be separated by 24 h (± 2 h).
Subjects will receive a 1st intravenous dose of Placebo and a 2nd intravenous dose of Placebo. Each dose will be separated by 24 h (± 2 h).
In the case, the high treatment regime is selected, subjects will receive a 1st intravenous dose of 4 mg/kg INM004 and a 2nd intravenous dose of 4 mg/kg of INM004. Each dose will be separated by 24 h (± 2 h). In the case, the low treatment regime is selected subjects will receive an intravenous dose of 4 mg/kg INM004
In the case, the high treatment regime is selected, subjects will receive a 1st intravenous dose of Placebo and a 2nd intravenous dose of Placebo, each dose separated by 24 h (± 2 h) In the case, low treatment regime is selected subjects will receive a single intravenous dose of Placebo