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 paediatric subjects with SBS who completed study TED-C14-006 or SHP633-301. |
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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 paediatric subjects with SBS who completed study TED-C14-006 or SHP633-301. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 or SHP633-301 studies (including subjects in the standard of care treatment arms). Subjects are considered to have completed SHP633-301 if they completed study assessments through week 24.
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 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 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 (EN) 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 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 (e.g., weight loss or growth failure) despite maximal tolerated EN 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.
5. The subject escaped during the follow-up period of SHP633-301 or during the follow-up period of a previous teduglutide treatment cycle within SHP633-304. |
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E.4 | Principal exclusion criteria |
Study Exclusion Criteria:
There are no exclusion criteria for this study.
Teduglutide Treatment Exclusion Criteria:
1. Body weight <5 kg at the pre-treatment visit.
2. Unresected gastrointestinal (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 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 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 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 3 months 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 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints:
- 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 |
End of each teduglutide treatment period (week 24 or EOT), and each study visit.
In addition, the Efficacy/PD endpoints will be analysed using the baseline of the Core study (TED-C14-006 or SHP633-301) and the baseline of each treatment cycle. |
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E.5.2 | Secondary end point(s) |
Safety Endpoints
- Adverse events, including those pertaining to GI symptoms
- Vital signs, including temperature, heart rate, blood pressure
- Body weight, height (or length), head circumference (up to 36 months of age) trends on growth charts, BMI; z-scores will be calculated for height (or length), weight, head circumference and BMI
- Laboratory safety data (i.e., clinical chemistry, haematology, and urinalysis)
- Urine output
- Stool output
- Antibodies to teduglutide
- Gastrointestinal-specific testing (teduglutide treatment eligible subjects only) including colonoscopy or sigmoidoscopy, abdominal ultrasound, and FOBT, upper GI series with small bowel follow through
Health Economics and Outcomes Research (HEOR) 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
Diarrhoea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each scheduled visit
The HEOR endpoints will be analysed using the Baseline of each
treatment cycle at approximately 12 week intervals (weeks 12 and 24 of each teduglutide treatment cycle, and every 12 weeks for subjects not on teduglutide). |
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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 | Yes |
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 |
arms for participants in non teduglutide treatment taking standard of care |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Belgium |
Canada |
Finland |
France |
Italy |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |