Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 and 2

Phase 2

Completed

• Conditions: Shiga Toxin Producing Bacterial Infection
• Interventions: Drug: Placebo; Drug: cαStx1/cαStx2

• Registration Number: NCT01252199
• Lead Sponsor: Thallion Pharmaceuticals

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.

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-29
• Study First Submitted QC: 2010-12-01
• Study First Posted: 2010-12-02
• Primary Completion: 2012-12
• Study Completion: 2013-02
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-23
• Last Update Posted: 2013-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	-
cαStx1/cαStx2	cαStx1/cαStx2	-

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability: Evaluation of number and type of adverse events and serious adverse events between arms and dosage cohorts	Up to 1 year	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.

Secondary Outcome Measures

Name	Time	Method
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