A long term extension study looking at the efficacy and safety of teduglutide in paediatric patients suffering from short bowel syndrome who took part in study TED-C14-006

Phase 1

• Conditions: Short Bowel Syndrome; MedDRA version: 20.0Level: PTClassification code 10049416Term: Short-bowel syndromeSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2016-000849-30-IT
• Lead Sponsor: Shire Human Genetic Therapies, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-06-16
• Last Update Posted: 5 March 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

Study Inclusion Criteria:
The subject will be considered eligible for the study if they meet all of the study inclusion criteria. Teduglutide treatment eligibility does not impact study eligibility.
1. Subject provides written informed consent (subject, parent or legal guardian and, as appropriate, informed assent) to participate in the study before completing any study-related procedures.
2. Subject completed the TED-C14-006 study (including subjects in the standard of care treatment arm).
3. Subject understands and is willing and able to fully adhere to study requirements

Teduglutide Eligibility Criteria:
Subjects are eligible for teduglutide treatment if at least one (=1) of the teduglutide treatment inclusion criteria, and none of the teduglutide treatment exclusion criteria, are met. In addition, the investigator and the subject (and/or parent or legal guardian, as appropriate) must agree to proceed with treatment.

Teduglutide Treatment Inclusion Criteria:
1. Subject is teduglutide-naïve, receiving parenteral support (PS), and unable to significantly reduce PS or advance enteral feeds (e.g., 10% or less change in PS or advance in feeds) for at least 3 months prior to and during the teduglutide pre-treatment visit, as assessed by the investigator. Transient instability for events such as interruption of central access or treatment for sepsis is allowed if the PS returns to within 10% of baseline prior to the event.
2. Subject was previously treated with teduglutide and at least one of the following criteria is satisfied:
a. Increasing PS requirements following teduglutide discontinuation.
b. Decreased PS requirement during prior teduglutide treatment, followed by cessation of improvement after teduglutide discontinuation.
c. Deteriorating nutritional status (e.g., weight loss or growth failure) despite maximal tolerated enteral nutrition following teduglutide discontinuation.
d. Deteriorating fluid or electrolyte status despite maximal tolerated enteral fluid and electrolyte intake following teduglutide discontinuation.
e. Severe diarrhoea related to teduglutide discontinuation.

Follow-up Period Escape Criteria:
At the discretion of the investigator, the follow-up period may be interrupted and the subject may proceed directly to the pre-treatment visit, if 1 of the following criteria is met:
1. Increasing PS requirements following teduglutide discontinuation
2. Deteriorating nutritional status (e.g., weight loss or growth failure) despite maximal tolerated enteral nutrition following teduglutide discontinuation.
3. Deteriorating fluid or electrolyte status despite maximal tolerated enteral fluid and electrolyte intake following teduglutide discontinuation.
4. Severe diarrhoea related to teduglutide discontinuation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 34
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Study Exclusion Criteria:
There are no exclusion criteria for this study.

Teduglutide Treatment Exclusion Criteria:
1. Body weight <10 kg at the pre-treatment visit.
2. Unresected gastrointestinal (GI) polyp, known polyposis condition, pre-malignant change, or malignancy, in the GI tract.
3. History of cancer in the previous 5 years except surgically curative skin cancers.
4. Serial transverse enteroplasty or other major intestinal surgery within 3 months preceding the teduglutide pre-treatment visit. Insertion of a feeding tube, anastomotic ulcer repair, minor intestinal resections =10 cm, and endoscopic procedures are allowed.
5. Intestinal or other major surgery planned or scheduled to occur during the 28-week cycle.
6. Clinically significant intestinal stricture or obstruction.
7. Clinically significant, active or recurrent pancreatic or biliary disease.
8. Active, severe, or unstable, clinically significant hepatic impairment or injury, including the following laboratory values at the pre-treatment visit:
a. Total bilirubin =2 × upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) =7 × ULN
c. Alanine aminotransferase (ALT) =7 × ULN
9. Renal dysfunction shown by results of an estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m2 at the pre-treatment visit.
10. Unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of subjects who had undergone ventricular or atrial septal defect repair, or patent ductus arteriosus (PDA) ligation.
11. Participation in a clinical study using an experimental drug (other than glutamine, Omegaven or Smoflipid) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to the pre-treatment visit and for the duration of the 28-week cycle.
12. Treatment with analogs of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) (not including teduglutide), insulin-like growth factor-1 (IGF-1), or growth hormone, within 3 months preceding the teduglutide pretreatment visit.
13. Treatment with octreotide or dipeptidyl peptidase 4 (DPP-4) inhibitors within 3 months prior to the pre-treatment visit.
14. Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
15. Known history of alcohol or other substance abuse within 1 year prior to the pre-treatment visit.
16. Pregnant or lactating female subjects.
17. Sexually active female subjects of child-bearing potential unwilling to use approved contraception during teduglutide treatment and for 30 days after the treatment period.
18. Any condition, disease, illness, or circumstance that in the investigator’s opinion puts the subject at any undue risk, prevents completion of the study, or interferes with analysis of the study results.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the long-term safety and tolerability of teduglutide treatment in paediatric subjects with SBS who completed study TED-C14-006.;Secondary Objective: The secondary objective of this study is to evaluate the long-term efficacy of teduglutide treatment in paediatric subjects with SBS who completed study TED-C14-006.;Primary end point(s): Efficacy endpoints:<br>- Reduction in PS volume of at least 20%<br>?- Absolute and relative change in PS volume<br>- Complete weaning off PS<br>- Change in days per week of PS;Timepoint(s) of evaluation of this end point: End of each teduglutide treatment period (week 24 or EOT), and each study visit.<br><br>In addition, the Efficacy/PD endpoints will be analysed using the baseline of the Core study (TED-C14-006) and the baseline of each treatment cycle.