Short Bowel Syndrome
Conditions
Keywords
SBS, Pediatric SBS, Short Bowel Syndrome
Brief summary
This will be an open label, 4-cohort study. Non-randomized subjects will receive teduglutide in each of the 3 active cohorts. An attempt will be made to enroll additional subjects into an observational cohort who will receive standard of care. Three doses of teduglutide are to be investigated for 12 weeks. All subjects will be screened prior to the start of treatment (SOT) to establish baseline characteristics including safety, eligibility and nutritional support parameters.
Interventions
DRUGteduglutide
Open label intervention. Each subject will be assigned to receive 0.0125, 0.025, or 0.05 mg/kg/day for the duration of the study
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) for at least 12 months prior to screening * Short bowel syndrome that requires parenteral nutrition/intravenous (PN/IV) support * Stable PN/IV support for at least 3 months prior to enrollment based upon the opinion of the investigator Key
Exclusion criteria
* Serial transverse enteroplasty or any other bowel lengthening procedure performed within the past 3 months * Unstable absorption due to cystic fibrosis, untreated Hirschsprung's disease or known DNA abnormalities (ie, Familial Adenomatous Polyposis, Fanconi syndrome) * Evidence of obstruction on upper gastrointestinal (GI) series done within 6 months prior to screening * Major gastrointestinal surgical intervention within 3 months prior to screening (insertion of feeding tube or endoscopic procedure is allowed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Parenteral Support (PN/IV) Volume at Week 16 | Baseline, Week 16 | Absolute change in PN/IV from the Baseline Visit to Week 16 Visit. |
| Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment | Baseline, End of Treatment | Absolute change in PN/IV from the Baseline Visit to End of Treatment Visit. |
| Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12 | Baseline, Week 12 | Percent change in PN/IV from the Baseline Visit to Week 12 Visit. |
| Percent Change in Parenteral Support (PN/IV) Volume at Week 16 | Baseline, Week 16 | Percent change in PN/IV from the Baseline Visit to Week 16 Visit. |
| Absolute Change in Parenteral Support (PN/IV) Volume at Week 12 | Baseline, Week 12 | Absolute change in PN/IV from the Baseline Visit to Week 12 Visit. |
| Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment | Baseline, End of Treatment | Percent change in PN/IV from the Baseline Visit to End of Treatment Visit. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Enteral Support (EN) Volume From Baseline at Week 16 | Baseline, Week 16 | Percent change in enteral support requirements at Week 16 (liters/week) |
| Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12 | Baseline, Week 12 | Absolute change in enteral support requirements at Week 12 (liters/week) |
| Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16 | Baseline, Week 16 | Absolute change in enteral support requirements at Week 16 (liters/week) |
| Percent Change in Enteral Support (EN) Volume From Baseline at Week 12 | Baseline, Week 12 | Percent change in enteral support requirements at Week 12 (liters/week) |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care SOC- no teduglutide therapy | 5 |
| Teduglutide 0.0125 mg/kg/Day Cohort 1 - Teduglutide 0.0125 mg/kg/day | 8 |
| Teduglutide 0.025 mg/kg/Day Cohort 2 - Teduglutide 0.025 mg/kg/day | 14 |
| Teduglutide 0.05 mg/kg/Day Cohort 3 - Teduglutide 0.05 mg/kg/day | 15 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Non-compliance | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Standard of Care | Teduglutide 0.0125 mg/kg/Day | Teduglutide 0.025 mg/kg/Day | Teduglutide 0.05 mg/kg/Day | Total |
|---|---|---|---|---|---|
| Age, Continuous | 2.2 years STANDARD_DEVIATION 0.45 | 5.1 years STANDARD_DEVIATION 4.55 | 4.6 years STANDARD_DEVIATION 3.43 | 4.5 years STANDARD_DEVIATION 3.16 | 4.7 years STANDARD_DEVIATION 3.5 |
| Age, Customized 13 to 17 years | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Age, Customized 1 to 3 years | 5 Participants | 4 Participants | 6 Participants | 7 Participants | 22 Participants |
| Age, Customized 4 to 12 years | 0 Participants | 3 Participants | 7 Participants | 7 Participants | 17 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 5 Participants | 8 Participants | 14 Participants | 12 Participants | 39 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 11 Participants | 8 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 8 / 8 | 14 / 14 | 15 / 15 |
| serious Total, serious adverse events | 3 / 5 | 3 / 8 | 6 / 14 | 8 / 15 |
Outcome results
Primary
Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment
Absolute change in PN/IV from the Baseline Visit to End of Treatment Visit.
Time frame: Baseline, End of Treatment
Population: Absolute change in PN/IV volume from baseline to End of Treatment based on prescribed data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment | 0.43 Liters/week | Standard Deviation 0.746 |
| Teduglutide 0.0125 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment | -0.43 Liters/week | Standard Deviation 0.864 |
| Teduglutide 0.025 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment | -2.73 Liters/week | Standard Deviation 1.916 |
| Teduglutide 0.05 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at End of Treatment | -2.4 Liters/week | Standard Deviation 3.498 |
Primary
Absolute Change in Parenteral Support (PN/IV) Volume at Week 12
Absolute change in PN/IV from the Baseline Visit to Week 12 Visit.
Time frame: Baseline, Week 12
Population: Absolute change in PN/IV volume from baseline to Week 12 based on prescribed data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change in Parenteral Support (PN/IV) Volume at Week 12 | 0.43 Liters/week | Standard Deviation 0.746 |
| Teduglutide 0.0125 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 12 | -0.50 Liters/week | Standard Deviation 0.91 |
| Teduglutide 0.025 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 12 | -2.78 Liters/week | Standard Deviation 1.985 |
| Teduglutide 0.05 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 12 | -2.57 Liters/week | Standard Deviation 3.564 |
Primary
Absolute Change in Parenteral Support (PN/IV) Volume at Week 16
Absolute change in PN/IV from the Baseline Visit to Week 16 Visit.
Time frame: Baseline, Week 16
Population: Absolute change in PN/IV volume from baseline to Week 16 based on prescribed data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change in Parenteral Support (PN/IV) Volume at Week 16 | 0.17 Liters/week | Standard Deviation 1.027 |
| Teduglutide 0.0125 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 16 | -0.56 Liters/week | Standard Deviation 0.885 |
| Teduglutide 0.025 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 16 | -2.56 Liters/week | Standard Deviation 1.917 |
| Teduglutide 0.05 mg/kg/Day | Absolute Change in Parenteral Support (PN/IV) Volume at Week 16 | -1.99 Liters/week | Standard Deviation 3.092 |
Primary
Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12
Percent change in PN/IV from the Baseline Visit to Week 12 Visit.
Time frame: Baseline, Week 12
Population: Percent change in PN/IV volume from baseline to Week 12 based on prescribed data - Intent-to-Treat Population (ITT), defined as all participants who were enrolled in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12 | 7.38 percent change | Standard Deviation 12.756 |
| Teduglutide 0.0125 mg/kg/Day | Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12 | -9.95 percent change | Standard Deviation 21.625 |
| Teduglutide 0.025 mg/kg/Day | Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12 | -37.34 percent change | Standard Deviation 26.422 |
| Teduglutide 0.05 mg/kg/Day | Percent Change in Parenteral Support [Parenteral Nutrition (PN)/Intravenous (IV)] Volume at Week 12 | -39.11 percent change | Standard Deviation 40.792 |
Primary
Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment
Percent change in PN/IV from the Baseline Visit to End of Treatment Visit.
Time frame: Baseline, End of Treatment
Population: Percent change in PN/IV volume from baseline to End of Treatment based on prescribed data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment | 7.38 percent change | Standard Deviation 12.756 |
| Teduglutide 0.0125 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment | -8.60 percent change | Standard Deviation 20.38 |
| Teduglutide 0.025 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment | -35.61 percent change | Standard Deviation 26.198 |
| Teduglutide 0.05 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at End of Treatment | -36.50 percent change | Standard Deviation 40.585 |
Primary
Percent Change in Parenteral Support (PN/IV) Volume at Week 16
Percent change in PN/IV from the Baseline Visit to Week 16 Visit.
Time frame: Baseline, Week 16
Population: Percent change in PN/IV volume from baseline to Week 16 based on prescribed data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change in Parenteral Support (PN/IV) Volume at Week 16 | 3.92 percent change | Standard Deviation 16.616 |
| Teduglutide 0.0125 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at Week 16 | -11.25 percent change | Standard Deviation 21.196 |
| Teduglutide 0.025 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at Week 16 | -33.85 percent change | Standard Deviation 27.017 |
| Teduglutide 0.05 mg/kg/Day | Percent Change in Parenteral Support (PN/IV) Volume at Week 16 | -31.80 percent change | Standard Deviation 39.264 |
Other Pre-specified
Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12
Absolute change in enteral support requirements at Week 12 (liters/week)
Time frame: Baseline, Week 12
Population: Absolute change of EN volume from baseline to Week 12 based on subject diary data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12 | 0.69 Liters/week | Standard Deviation 0.715 |
| Teduglutide 0.0125 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12 | 2.67 Liters/week | Standard Deviation 4.412 |
| Teduglutide 0.025 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12 | 2.64 Liters/week | Standard Deviation 3.22 |
| Teduglutide 0.05 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 12 | 0.97 Liters/week | Standard Deviation 1.127 |
Other Pre-specified
Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16
Absolute change in enteral support requirements at Week 16 (liters/week)
Time frame: Baseline, Week 16
Population: Absolute change of EN volume from baseline to Week 16 based on subject diary data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16 | 0.84 Liters/week | Standard Deviation 0.624 |
| Teduglutide 0.0125 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16 | 4.56 Liters/week | Standard Deviation 5.384 |
| Teduglutide 0.025 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16 | 2.47 Liters/week | Standard Deviation 3.403 |
| Teduglutide 0.05 mg/kg/Day | Absolute Change in Enteral Support (EN) Volume From Baseline at Week 16 | 0.91 Liters/week | Standard Deviation 0.968 |
Other Pre-specified
Percent Change in Enteral Support (EN) Volume From Baseline at Week 12
Percent change in enteral support requirements at Week 12 (liters/week)
Time frame: Baseline, Week 12
Population: Percent change of EN volume from baseline to Week 12 based on subject diary data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change in Enteral Support (EN) Volume From Baseline at Week 12 | 16.82 percent change | Standard Deviation 14.921 |
| Teduglutide 0.0125 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 12 | 23.50 percent change | Standard Deviation 22.06 |
| Teduglutide 0.025 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 12 | 50.93 percent change | Standard Deviation 61.416 |
| Teduglutide 0.05 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 12 | 57.96 percent change | Standard Deviation 44.953 |
Other Pre-specified
Percent Change in Enteral Support (EN) Volume From Baseline at Week 16
Percent change in enteral support requirements at Week 16 (liters/week)
Time frame: Baseline, Week 16
Population: Percent change of EN volume from baseline to Week 16 based on subject diary data - Intent-to-Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Percent Change in Enteral Support (EN) Volume From Baseline at Week 16 | 52.06 percent change | Standard Deviation 66.194 |
| Teduglutide 0.0125 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 16 | 60.30 percent change | — |
| Teduglutide 0.025 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 16 | 43.98 percent change | Standard Deviation 78.599 |
| Teduglutide 0.05 mg/kg/Day | Percent Change in Enteral Support (EN) Volume From Baseline at Week 16 | 58.93 percent change | Standard Deviation 63.927 |