E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049416 |
E.1.2 | Term | Short-bowel syndrome |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
The primary objective of the study is to evaluate the long-term safety and tolerability of teduglutide treatment in pediatric subjects with SBS who completed TED-C13-003. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the long-term efficacy of teduglutide treatment in pediatric subjects with SBS who completed TED-C13-003. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Study Inclusion Eligibility Criteria 1. Subject provides written informed consent (subject, parent or legal guardian and, as appropriate, subject informed assent) to participate in the study before completing any study-related procedures. 2. Subject completed the TED-C13-003 study (including subjects in the standard of care treatment arm). 3. Subject understands and is willing and able to fully adhere to study requirements as defined in the protocol. Teduglutide Treatment Inclusion Criteria 1. Subject is receiving PS and unable to significantly reduce PS or advance enteral feeds (eg, 10% or less change in PS or advance in feeds) for at least 3 months prior to and during the teduglutide pretreatment 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 1 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 (eg, 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 diarrhea related to teduglutide discontinuation |
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E.4 | Principal exclusion criteria |
1. Body weight <10 kg at the pretreatment visit 2. Unresected GI polyp, known polyposis condition, premalignant 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 pretreatment 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 pretreatment 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 pretreatment 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 Teduglutide) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to the pretreatment 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 1 month preceding the teduglutide pretreatment visit 13. Treatment with octreotide or dipeptidyl peptidase 4 (DPP-4) inhibitors within 3 months prior to the pretreatment 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 pretreatment 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 period18. 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 Follow-up Period Escape Criteria At the discretion of the investigator, the follow-up period may be interrupted or omitted and the subject may proceed directly to the pretreatment visit, if ≥1 of the following criteria is met: 1. Increasing PS requirements following teduglutide discontinuation 2. Deteriorating nutritional status (eg, 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 diarrhea related to teduglutide discontinuation 5. The subject escaped during the follow up period of a previous teduglutide treatment cycle within SHP633-303 |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Reduction in PS volume of at least 20% - Absolute and relative change in PS volume - Complete weaning off PS - Change in days per week of PS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 12-week intervals during the retrospective observation period, 2) the end of each prospective teduglutide treatment period (Week 24/EOT), and 3) each prospective study visit. |
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E.5.2 | Secondary end point(s) |
Safety Endpoints 1. Adverse events, including those pertaining to GI symptoms 2. Vital signs, including body temperature, heart rate, and blood pressure 3. Laboratory safety data (i.e., clinical chemistry, haematology, and urinalysis) 4. Urine output 5. Stool output 6. Antibodies to teduglutide 7. Gastrointestinal-specific testing including faecal occult blood testing and colonoscopy or sigmoidoscopy, as needed
Other safety endpoints: a. All treatment-related AEs b. All SAEs c. All AESIs
More safety endpoints A. Z-scores for height (or length), weight, head circumference (up to 36 months of age), and body mass index
Health economics and outcomes research endpoints: Change in Pediatric Quality of Life Inventory (PedsQL) score Change in PedsQL Family Impact Module score Change in PedsQL Gastrointestinal Symptoms Module Sub-Scales scores: Food and drink limits Diarrhea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
safety end points 1 to 7 will be analysed from the beginning of the prospective study period
safety endpoints a, b & c will be analysed from the end of the core study (Week 16/EOS) to the beginning of the prospective study period
safety endpoint A. will be analysed relative to the baseline of the core study (TED-C13-003)
Health economics and outcomes research endpoints will be analysed at approximately 12-week intervals (Weeks 12 and 24 of each teduglutide treatment cycle, and every 12 weeks for subjects not on teduglutide), relative to the baseline of the prospective study period. The beginning of each treatment cycle (CxD1) will be an additional baseline. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
arm for participants in non teduglutide treatment taking standard of care only |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |