Clinical Trials Register

Summary
EudraCT Number:	2011-006094-26
Sponsor's Protocol Code Number:	CTP_STX005/STX005EXT
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-02-10
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2011-006094-26

A.3

Full title of the trial

A Phase II Study of Chimeric Monoclonal Antibodies to Shiga Toxins 1 (caStx1) and 2 (caStx2) Administered Concomitantly to Children with Shiga Toxin-Producing Bacterial (STPB) Infection and Bloody Diarrhea (SHIGATEC trial).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical Study of Antibodies to Shiga Toxins 1 and 2

A.4.1

Sponsor's protocol code number

CTP_STX005/STX005EXT

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01252199

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/308/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Thallion Pharmaceuticals Inc
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Thallion Pharmaceuticals Inc
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Thallion Pharmaceuticals Inc
B.5.2	Functional name of contact point	Didier Reymond, MD
B.5.3	Address:
B.5.3.1	Street Address	1375 Transcanada Highway, Suite 200
B.5.3.2	Town/ city	Dorval, Québec
B.5.3.3	Post code	H9P 2W8
B.5.3.4	Country	Canada
B.5.4	Telephone number	+1 5142283631
B.5.5	Fax number	+15142283622
B.5.6	E-mail	dreymond@thallion.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/301
D.3 Description of the IMP
D.3.1	Product name	Chimeric monoclonal antibodies to shiga-toxin 1 and 2
D.3.2	Product code	caStx1/caStx2
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1351470-16-0
D.3.9.3	Other descriptive name	caStx1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1351470-17-1
D.3.9.3	Other descriptive name	caStx2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of Shiga toxin-mediated complications resulting from Shiga toxin producing bacterial infections.

E.1.1.1

Medical condition in easily understood language

Infection caused by bacteria producing Shiga toxins

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10019515
E.1.2	Term	Hemolytic uremic syndrome
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the safety and tolerability of two different intravenous dose levels of a combined caStx1/caStx2 preparation in separate groups of children presenting with STPB infection

E.2.2

Secondary objectives of the trial

To assess efficacy by examining for each patient a composite endpoint defined as either of the following events:
1. Presence of macroscopic bloody diarrhea more than 48 hours post-treatment, or
2. Presence of at least 2 out of 3 criteria of HUS defined as: a/ serum creatinine > ULN adjusted for age and gender, b/ platelets < 150 x 10^3/µL, and c/ hemolytic anemia (hematocrit < 30% with evidence of hemolysis (as indicated by LDH above the upper limit of normal age or the finding of schistocytes on peripheral smear in an anemic child).

To evaluate the PK characteristics of caStx1 and caStx2
To assess the frequency of induction of human anti-chimeric antibodies (HACA)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Extension study (STX005EXT)

To assess at 6 and 12 months the incidence of long term kidney injury: 1/ arterial hypertension; 2/ chronic renal insufficiency; 3/ end-stage renal failure between groups.

To assess at 6 and 12 months the long-term presence of HACA and incidence of potential treatment-induced immune-complex diseases.

E.3

Principal inclusion criteria

1. Written, signed and dated informed consent by a parent or legally acceptable representative and age appropriate patient assent
2. Age between 6 months and 18 years (inclusively)
3. Bloody diarrhea (by visual inspection) for no more than 36 hours prior to screening.
4. Females of child-bearing potential and sexually active must have negative urine pregnancy test prior to administration of study medication. Abstain from sexual activity or use of acceptable contraceptive measures.
5. Detection of Shiga toxin (Stx1 and/or Stx2) in stool by a rapid diagnostic test (Meridian Premier EHEC Assay) or antigens from Shiga toxin producing E Coli 0157 by the ImmunoCard STAT E coli 0157 Plus test

E.4

Principal exclusion criteria

1. Laboratory findings compatible with development of at least two out of the three following criteria that define HUS: hemolytic anemia, thrombocytopenia and nephropathy
2. Bloody-diarrhea suspected not to be caused by STPB but by other organisms or preexisting diseases
3. History of renal disease or malformation. Active renal disease including infection, and isolated macrohematuria
4. Family history of proven or suspected hereditary HUS or TTP
5. Clinically significant and/or uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophtalmologic, immunologic or other significant disease
6. History of chronic/recurrent hemolytic anemia or thrombocytopenia
7. Ongoing treatment for malignancy
8. History of chronic inflammatory bowel disease
9. Prior treatment with murine, chimeric, or humanized antibody
10. Breastfeeding women

E.5 End points

E.5.1

Primary end point(s)

Safety parameters will include the occurence of AEs and clinical and biological indicators such as vital signs, body weight, physical exam, ECGs, laboratory parameters by age groups: 6 months - 23 months, 2-11 years, 12-18 years

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1, 2, 3, 4, 6, 8, 15, 22, 29 and 57 for the core study
Month 6 and 12 for the extension study

E.5.2

Secondary end point(s)

Composite endpoint (see E.2.2)
Incidence of (isolated) serum creatinine
Incidence of (isolated) hemolytic anemia
Incidence and duration of (isolated) thrombocytopenia
Incidence of complete HUS (3 out of 3 criteria)
Isolated presence of (macroscopic) bloody diarrhea more than 48h post treatment
Isolated presence of at least 2 out of 3 crietria for HUS
Incidence and duration of hospitalization
Incidence and duration of dialysis
Incidence of seizures
Incidence and number of red blood cell transfusions
Treatment effect of the antibodies according to the time elapsed from the first bloody diarrhea episode to treatment (end of infusion)
Incidence of long term kidney injury
Incidence of deaths
Development of HACA per age groups
PK characteristics of caStx1 and caStx2 by age groups
Complement levels by age groups

E.5.2.1

Timepoint(s) of evaluation of this end point

Incidence of long-term kidney injury: 6 and 12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

The extension part of the study (STX005EXT) will be open-label

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Argentina

Chile

Peru

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS extension study (STX005EXT)

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No plan for treatment or care after the subject has ended the participation in the trial is planned

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Argentina

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