Clinical trial NCT01252199: Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 and 2
Official title: A Phase II Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 (cαStx1) and 2 (cαStx2) Administered Concomitantly to Children With Shiga Toxin-Producing Bacterial (STPB) Infection and Bloody Diarrhea (SHIGATEC Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Shiga Toxin Producing Bacterial Infection
Keywords: Shigamabs
Monoclonal
Antibodies
Shiga
Toxin
E.coli
HUS
Bloody
Diarrhea
Lead sponsor: Thallion Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: LFB Biotechnologies, SAS
First posted: 2010-12-02
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the safety and efficacy of cαStx1 and cαStx2 administered concomitantly in children presenting early signs of Shiga Toxin-Producing Bacterial (STPB) Infection.

Detailed description: Currently, there is no etiological treatment of STPB-induced HUS. Ideally, such treatment would be started in the early phase of the infection and would protect against both types of toxins and all of their variants. The chimeric anti-Shiga toxins 1 (cαStx1) and 2 (cαStx2) antibodies are intended to be administered as a single infusion and provide simultaneous protection against the two Shiga toxins (Stx1 and Stx2) by decreasing the incidence and severity of Shiga toxin-mediated clinical events including bloody diarrhea/hemorrhagic colitis and Hemolytic Uremic Syndrome (HUS) and associated sequelae.

Eligibility criteria: Inclusion Criteria:

1. Bloody diarrhea (by visual inspection) for no more than 36 hours prior to screening (signature of the informed consent).
2. Detection of Shiga toxin (Stx1 and/or Stx2) in stool

Exclusion Criteria:

1. Laboratory findings compatible with development of at least two out of three following criteria that define Hemolytic Uremic Syndrome (HUS):

   Hemolytic Anemia: hematocrit \< 30% with evidence of hemolysis (as indicated by Lactate Dehydrogenase (LDH) above the upper limit of normal for age or the finding of schistocytes on peripheral smear); Thrombocytopenia: platelet count \<150 x 103/uL; Nephropathy: serum creatinine \> Upper Limit Normal (ULN) adjusted for age and gender.
2. Bloody-diarrhea suspected not to be caused by Shiga Toxin-Producing Bacteria (STPB) but by other organisms or preexisting diseases.
3. Family history of proven or suspected hereditary Hemolytic Uremic Syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP).
4. History of chronic/recurrent hemolytic anemia or thrombocytopenia.

Primary outcomes:
measure: Safety and Tolerability: Evaluation of number and type of adverse events and serious adverse events between arms and dosage cohorts
timeFrame: Up to 1 year
Secondary outcomes:
measure: Efficacy: Comparison of clinical event rates (Hemolytic Uremic Syndrome, Bloody Diarrhea) and associated sequelae between arms and dosage cohorts in children presenting with Shiga Toxin-Producing Bacterial (STPB) infection.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Bahia Blanca
country: Argentina
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Mendoza
country: Argentina
city: Parana
country: Argentina
city: Tucuman
country: Argentina
city: Concepcion
country: Chile
city: Santiago
country: Chile
city: Valparaiso
country: Chile
city: Lima
country: Peru
Study officials:
References:
citation: Imdad A, Mackoff SP, Urciuoli DM, Syed T, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD012997. doi: 10.1002/14651858.CD012997.pub2.