Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 and 2

Sponsor

Thallion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01252199

Collaborator

LFB Biotechnologies, SAS (Other)

Enrollment

Locations

Arms

Duration (Months)

4.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Shiga Toxin Producing Bacterial Infection	Drug: cαStx1/cαStx2 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Control	Drug: Placebo Placebo administered over 1 hour + standard of care

Arm

Intervention/Treatment

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

Placebo Comparator: Control

Drug: Placebo

Placebo administered over 1 hour + standard of care

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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.

Bloody-diarrhea suspected not to be caused by Shiga Toxin-Producing Bacteria (STPB) but by other organisms or preexisting diseases.
Family history of proven or suspected hereditary Hemolytic Uremic Syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP).
History of chronic/recurrent hemolytic anemia or thrombocytopenia.

Contacts and Locations

Locations

	City	Country
1	Bahia Blanca	Argentina
2	Buenos Aires	Argentina
3	Cordoba	Argentina
4	La Plata	Argentina
5	Mendoza	Argentina
6	Parana	Argentina
7	Tucuman	Argentina
8	Concepcion	Chile
9	Santiago	Chile
10	Valparaiso	Chile
11	Lima	Peru