E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Short Bowel Syndrome (SBS) |
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E.1.1.1 | Medical condition in easily understood language |
Short Bowel Syndrome (SBS) |
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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 objectives of this trial are to evaluate the safety, efficacy/pharmacodynamics and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral support. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent by the parent or legal guardian.
2. Male or female infant 4 to 12 months corrected gestational age at screening.
3. Weight at least 5 kg and weight-for-length Z-score greater than -2 at screening and baseline.
4. Short bowel syndrome with dependence on parenteral support to provide at least 50% of fluid or caloric needs.
5. Stable Parenteral Nutrition (PN) requirements for at least 1 month prior to screening, defined as a ≤10% change in the weight-normalized parenteral total fluid and caloric intake, despite attempts to wean PN, notwithstanding transient instability for events such as sepsis or interruption of
central venous access.
6. Lack of terminal ileum and ileocecal valve.
7. Parent or legal guardian understands and is willing and able to fully adhere to study requirements as defined in this protocol. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with teduglutide.
2. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc.
3. Severe, known dysmotility syndrome, such as pseudo-obstruction or persistent, severe, active gastroschisis-related dysmotility, that is the primary contributing factor to feeding intolerance and inability to reduce parenteral support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding.
4. Inability to advance oral or enteral feeding due to lack of access to the gut, such as oral aversion in the absence of a feeding tube.
5. Intestinal obstruction or clinically significant intestinal stenosis.
6. Major gastrointestinal surgical intervention, such as serial transverse enteroplasty or major intestinal resection or anastomosis, within 3 months prior to screening or planned during the study period.
7. Unstable cardiac disease.
8. Renal dysfunction, defined as estimated glomerular filtration rate <50 mL/min/1.73 m2.
9. Biliary obstruction, stenosis, or malformation.
10. Clinically significant pancreatic disease.
11. Severe hepatic dysfunction or portal hypertension, defined by at least 2 of the following parameters:
a. International normalized ratio (INR) >1.5 not corrected with parenteral vitamin K
b. Platelet count <100×10^3/μL due to portal hypertension
c. Presence of clinically significant gastric or esophageal varices
d. Documented cirrhosis
12. Persistent cholestasis defined as conjugated bilirubin >4 mg/dL (>68 μmol/L) over a 2 week period.
13. More than 3 serious complications of intestinal failure (e.g., catheter-associated bloodstream infections, interruption of nutrition due to feeding intolerance, catheter-associated thrombosis, severe fluid or electrolyte disturbances) within 1 month prior to or during screening.
14. A history of cancer or a known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of gastrointestinal cancer (including hepatobiliary and pancreatic cancers).
15. Concurrent treatment with glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); insulin-like growth factor-1 (IGF-1); growth hormone, somatostatin, or analogs of these hormones; or glutamine.
16. Participation in a clinical study using an experimental drug within 3 months or 5.5 half-lives of the experimental drug, whichever is longer.
17. Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
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) |
Reduction in weight-normalized PN fluid volume by at least 20% from baseline at Week 24/EOT (end of treatment) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Reduction in weight-normalized parenteral calories by at least 20% from baseline to Week 24/EOT
- Achievement of enteral autonomy by week 24
- Change in weight-normalized parenteral fluid volume from baseline to each visit
- Change in weight-normalized parenteral calories from baseline to each visit
- Change in weight-normalized enteral fluid volume from baseline to each visit
- Change in weight-normalized enteral caloric intake from baseline to each visit
- Increase in weight-normalized enteral fluid intake by at least 20% from baseline to Week 24/EOT
- Increase in weight-normalized enteral caloric intake by at least 20% from baseline to Week 24/EOT
Pharmacokinetics
The pharmacokinetic endpoint is plasma teduglutide concentration at nominal time point.
Safety
Safety endpoints consist of the following:
- Adverse events (AEs)
- Physical examinations
- Vital signs
- Weight, length, head circumference, and weight-for-length Z-scores (corrected for gestational age)
- Laboratory safety data (biochemistry and haematology)
- Urine output
- Stool (including mixed) output
- Antibodies to teduglutide
Health Economics and Outcomes Research
Health economics and outcomes research (HEOR) endpoints include the following:
- Cumulative number of hospitalization days during the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
each visit and week 24/EoT |
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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 | Yes |
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 |
1 arm standard of care and 1 arm on teduglutide |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |