Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 and 2

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)

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.

Study Overview

• Status: Completed
• Conditions: Shiga Toxin Producing Bacterial Infection
• Intervention / Treatment: Drug: cαStx1/cαStx2; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Bahia Blanca, Argentina
  • Buenos Aires, Argentina
  • Cordoba, Argentina
  • La Plata, Argentina
  • Mendoza, Argentina
  • Parana, Argentina
  • Tucuman, Argentina
• Chile
  • Concepcion, Chile
  • Santiago, Chile
  • Valparaiso, Chile
• Peru
  • Lima, Peru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control	Drug: Placebo; Placebo administered over 1 hour + standard of care
EXPERIMENTAL: cαStx1/cαStx2	Drug: cαStx1/cαStx2; cαStx1/cαStx2 administered concomitantly at a dose of 1 mg/kg (low dose cohort) or 3 mg/kg (high dose cohort)per antibody over 1 hour + standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: Evaluation of number and type of adverse events and serious adverse events between arms and dosage cohorts	Evaluation of the safety and tolerability of two different intravenous dose levels of a combined cαStx1/cαStx2 preparation in separate groups of children presenting with Shiga Toxin-Producing Bacterial (STPB) infection.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	Up to 1 year

Collaborators and Investigators

• Sponsor: Thallion Pharmaceuticals
• Collaborators: LFB Biotechnologies, SAS

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (ESTIMATE): December 2, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 25, 2013
• Last Update Submitted That Met QC Criteria: April 23, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Diarrhea; Antibodies; E.coli; Monoclonal; HUS; Toxin; Shigamabs; Shiga; Bloody
• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Bacterial Infections
• Other Study ID Numbers: CTP_STX005/STX005EXT