Short Bowel Syndrome
Conditions
Keywords
Teduglutide, pediatric, GLP-2, parenteral support, Short Bowel Syndrome, short gut syndrome, short gut, SBS, parenteral nutrition
Brief summary
Teduglutide is approved for treatment of adults with short bowel syndrome (SBS). The purpose of this study is to evaluate the safety and efficacy of teduglutide in children up to the age of 17 with SBS who are dependent on parenteral support. Subjects may choose whether to receive the study drug or to participate in a standard-of-care arm. All participants who complete the study may be eligible to receive the study drug in a long-term extension study.
Interventions
DRUGTeduglutide 0.05mg/kg
0.05 mg/kg
DRUGTeduglutide 0.025 mg/kg
0.025 mg/kg
OTHERStandard of Care
Observational cohort for the 24-week treatment period and 4 week follow-up.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent by a parent or guardian or emancipated minor prior to any study-related procedures 2. When applicable, an informed assent by the subject (as deemed appropriate by the Ethics Committee/Institutional Review Board) prior to any study-related procedures 3. Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) 4. Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs prior to screening 5. Stable PN/IV support, defined as inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 3 months prior to and during screening, as assessed by the investigator. 6. Sexually active female subjects of child-bearing potential (in the teduglutide treatment arm only) must use medically acceptable methods of birth control during and 4 weeks after the treatment period
Exclusion criteria
1. Subjects who are not expected to be able to advance oral or tube feeding regimens 2. Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening 3. Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support 4. Unstable absorption due to cystic fibrosis or known DNA abnormalities 5. 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. 6. Evidence of clinically significant obstruction on upper GI series done within 6 months prior to screening. 7. Major GI surgical intervention including significant intestinal resection within 3 months prior to the screening visit (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections ≤ 10 cm, or endoscopic procedure is allowed). 8. Unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of subjects who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation. 9. History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ non aggressive and surgically resected cancer. 10. Pregnant or lactating female subjects (in the teduglutide treatment arm only). 11. Participation in a clinical study using an experimental drug (other than glutamine or Omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to screening, and for the duration of the study. 12. Previous use of teduglutide or native/synthetic glucagon-like peptide-2 (GLP-2) 13. Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening 14. Previous use of octreotide, or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening 15. Subjects with active Crohn's disease who had been treated with biological therapy (eg, antitumor necrosis factor \[anti-TNF\]) within the 6 months prior to the screening visit 16. Subjects with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening 17. More than 3 SBS-related or PN-related hospital admissions (eg, documented infection-related catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to the screening visit 18. Any major unscheduled hospital admission which affects parenteral support requirements within 1 month prior to or during screening, excluding uncomplicated treatment of bacteremia, central line replacement/repair, or issues of similar magnitude in an otherwise stable subject 19. Body weight \< 10 kg at the screening and baseline visits 20. Signs of active severe or unstable, clinically significant hepatic impairment during the screening period, as indicated by any of the following laboratory test results : 1. Total bilirubin (TBL) ≥ 2 x upper limit of normal (ULN) 2. Aspartate aminotransferase (AST) ≥ 7x ULN 3. Alanine aminotransferase (ALT) ≥ 7x ULN For subjects with Gilbert's disease: 4. Indirect (unconjugated) bilirubin ≥ 2x ULN 21. Signs of known continuous active or unstable, clinically significant renal dysfunction shown by results of an estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m2. 22. Parent(s) and/or subjects who are not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements 23. Unstable, clinically significant active, untreated pancreatic or biliary disease 24. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Baseline through Week 24 | Reduction in weight-normalized PN/IV volume was performed using both participant diary and investigator prescribed data. Number of participants who achieved at least a 20% reduction in weight-normalized PN/IV volume between the baseline and week 24/EOT visit were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Week 24 | A participant was considered to have achieved independence from PN/IV support (completely weaned off PN/IV) if the investigator prescribed no PN/IV at EOT and there was no use of PN/IV recorded in the participant diary during the week prior to EOT. |
| Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Baseline, Week 24 | Change in PN/IV volume was reported based on the participant diary and the investigator prescribed data. |
| Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Baseline, Week 24 | Change in PN/IV caloric intake was reported based on the participant diary and the investigator prescribed data. |
| Change From Baseline in Plasma Citrulline Levels at Week 24 | Baseline, Week 24 | Plasma citrulline level was reported. |
| Change From Baseline in Enteral Nutrition Volume at Week 24 | Baseline, Week 24 | Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported. |
| Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Baseline, Week 24 | Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported. |
| Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Week 24, Week 28 | Change in PN/IV volume was reported. |
| Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Week 24, Week 28 | Change in PN/IV caloric intake was reported. |
| Change From Week 24 in Plasma Citrulline Levels at Week 28 | Week 24, Week 28 | Change in plasma citrulline level was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study treatment up to 28 weeks | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or worsened on or after the date of first dose for treatment groups and those that started or worsened on or after the baseline visit for standard of care group. |
| Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Week 24, Week 28 | Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported. |
| Change From Baseline in Body Weight Z-score at Week 28 | Baseline, Week 28 | Body weight z-score is a measure of relative weight adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. |
| Change From Baseline in Body Height Z-score at Week 28 | Baseline, Week 28 | Body height z-score is a measure of relative height adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. |
| Change From Baseline in Head Circumference Z-score at Week 28 | Baseline, Week 28 | Head circumference z-score is a measure of relative head circumference adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. Head circumference was collected only for participants of less than or equal to (\<=) 36 months of age at the time of measurement. |
| Change From Baseline in Body Mass Index (BMI) Z-score at Week 28 | Baseline, Week 28 | BMI z-score is a measure of relative BMI adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. |
| Change From Baseline in Participants' Stool Consistency at Week 28 | Baseline, Week 28 | Stool consistency was assessed by typical stool form based on Bristol Stool Form Scale: 1 - Separate hard lumps, hard to pass, 2 - Sausage-shaped, but lumpy, 3 - Like a sausage but with cracks on the surface, 4 - Like a sausage or snake, smooth and soft, 5 - Soft blobs with clear-cut edges, 6 - Fluffy pieces with ragged edges, a mushy stool, 7 - Watery, no solid pieces, entirely liquid. |
| Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Baseline, Week 24 | The mean duration of the PN/IV infusions in hours, on the days when PN/IV was administered was reported. |
| Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Baseline, Week 24 | The number of days per week of PN/IV infusions were reported. |
| Change From Week 24 in Enteral Nutrition Volume at Week 28 | Week 24, Week 28 | Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported. |
Countries
Belgium, Canada, Finland, Germany, Italy, United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at 27 study centers in the United States, Belgium, Canada, the United Kingdom, Finland, Germany and Italy between 03 June 2016 (first participant first visit) and 18 August 2017 (last participant last visit).
Pre-assignment details
Overall, 59 participants were enrolled; 50 in the teduglutide treatment arm (24 participants in the 0.025 milligram per kilogram per day (mg/kg/day) dose group and 26 participants in the 0.05 mg/kg/day dose group)and 9 in the standard of care arm.
Participants by arm
| Arm | Count |
|---|---|
| 0.025 mg/kg/Day Teduglutide Participants received 0.025 mg/kg/day of teduglutide subcutaneously for 24 weeks along with standard medical therapy. | 24 |
| 0.05 mg/kg/Day Teduglutide Participants received 0.05 mg/kg/day of teduglutide subcutaneously for 24 weeks along with standard medical therapy. | 26 |
| Standard of Care Participants received standard medical therapy. | 9 |
| Total | 59 |
Baseline characteristics
| Characteristic | Total | Standard of Care | 0.05 mg/kg/Day Teduglutide | 0.025 mg/kg/Day Teduglutide |
|---|---|---|---|---|
| Age, Continuous | 6.3 Years STANDARD_DEVIATION 3.76 | 5.7 Years STANDARD_DEVIATION 4.72 | 6.2 Years STANDARD_DEVIATION 3.67 | 6.6 Years STANDARD_DEVIATION 3.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 4 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 2 Participants | 20 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 3 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Customized Asian | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Customized Black or African American | 7 Participants | 1 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Customized Not allowed based on local regulations | 7 Participants | 3 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Customized Other | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Customized White | 39 Participants | 2 Participants | 21 Participants | 16 Participants |
| Sex: Female, Male Female | 18 Participants | 3 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 41 Participants | 6 Participants | 19 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 26 | 0 / 9 |
| other Total, other adverse events | 24 / 24 | 23 / 26 | 9 / 9 |
| serious Total, serious adverse events | 15 / 24 | 20 / 26 | 4 / 9 |
Outcome results
Primary
Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24
Reduction in weight-normalized PN/IV volume was performed using both participant diary and investigator prescribed data. Number of participants who achieved at least a 20% reduction in weight-normalized PN/IV volume between the baseline and week 24/EOT visit were reported.
Time frame: Baseline through Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | 13 Participants |
| 0.025 mg/kg/Day Teduglutide | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | 13 Participants |
| 0.05 mg/kg/Day Teduglutide | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | 18 Participants |
| 0.05 mg/kg/Day Teduglutide | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | 18 Participants |
| Standard of Care | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | 1 Participants |
| Standard of Care | Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | 2 Participants |
Secondary
Change From Baseline in Body Height Z-score at Week 28
Body height z-score is a measure of relative height adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Time frame: Baseline, Week 28
Population: Safety analysis population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Body Height Z-score at Week 28 | 0 Z-score | Standard Deviation 0.29 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Body Height Z-score at Week 28 | 0.05 Z-score | Standard Deviation 0.45 |
| Standard of Care | Change From Baseline in Body Height Z-score at Week 28 | 0.16 Z-score | Standard Deviation 0.66 |
Secondary
Change From Baseline in Body Mass Index (BMI) Z-score at Week 28
BMI z-score is a measure of relative BMI adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Time frame: Baseline, Week 28
Population: Safety analysis population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Body Mass Index (BMI) Z-score at Week 28 | -0.13 Z-score | Standard Deviation 0.57 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Body Mass Index (BMI) Z-score at Week 28 | -0.22 Z-score | Standard Deviation 0.7 |
| Standard of Care | Change From Baseline in Body Mass Index (BMI) Z-score at Week 28 | -0.25 Z-score | Standard Deviation 1.42 |
Secondary
Change From Baseline in Body Weight Z-score at Week 28
Body weight z-score is a measure of relative weight adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Time frame: Baseline, Week 28
Population: Safety analysis population included all participants who received at least 1 dose of teduglutide and had undergone at least 1 post-baseline safety assessment in teduglutide treatment group or participants who had undergone at least 1 post-baseline safety assessment in standard of care treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Body Weight Z-score at Week 28 | -0.12 Z-score | Standard Deviation 0.41 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Body Weight Z-score at Week 28 | -0.18 Z-score | Standard Deviation 0.59 |
| Standard of Care | Change From Baseline in Body Weight Z-score at Week 28 | -0.05 Z-score | Standard Deviation 0.37 |
Secondary
Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
The number of days per week of PN/IV infusions were reported.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | -0.88 Days per week (Days/week) | Standard Deviation 1.78 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | -0.79 Days per week (Days/week) | Standard Deviation 1.62 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | -1.34 Days per week (Days/week) | Standard Deviation 2.24 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | -1.42 Days per week (Days/week) | Standard Deviation 2.32 |
| Standard of Care | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | 0 Days per week (Days/week) | Standard Deviation 0 |
| Standard of Care | Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | 0 Days per week (Days/week) | Standard Deviation 0 |
Secondary
Change From Baseline in Enteral Nutrition Caloric Intake at Week 24
Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Participant Diary | 8.43 Kilocalorie per kilogram per day | Standard Deviation 14.39 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Investigator Prescribed | 7.29 Kilocalorie per kilogram per day | Standard Deviation 15.88 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Participant Diary | 12.98 Kilocalorie per kilogram per day | Standard Deviation 18.93 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Investigator Prescribed | 11.47 Kilocalorie per kilogram per day | Standard Deviation 21.13 |
| Standard of Care | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Participant Diary | 4.22 Kilocalorie per kilogram per day | Standard Deviation 13.75 |
| Standard of Care | Change From Baseline in Enteral Nutrition Caloric Intake at Week 24 | Investigator Prescribed | 6.66 Kilocalorie per kilogram per day | Standard Deviation 14.77 |
Secondary
Change From Baseline in Enteral Nutrition Volume at Week 24
Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Volume at Week 24 | Participant Diary | 7.69 Milliliter per kilogram per day | Standard Deviation 13.46 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Volume at Week 24 | Investigator Prescribed | 7.67 Milliliter per kilogram per day | Standard Deviation 17.77 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Volume at Week 24 | Participant Diary | 10.96 Milliliter per kilogram per day | Standard Deviation 16.59 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Enteral Nutrition Volume at Week 24 | Investigator Prescribed | 8.17 Milliliter per kilogram per day | Standard Deviation 17.87 |
| Standard of Care | Change From Baseline in Enteral Nutrition Volume at Week 24 | Participant Diary | 0.74 Milliliter per kilogram per day | Standard Deviation 5.91 |
| Standard of Care | Change From Baseline in Enteral Nutrition Volume at Week 24 | Investigator Prescribed | 0.33 Milliliter per kilogram per day | Standard Deviation 0.9 |
Secondary
Change From Baseline in Head Circumference Z-score at Week 28
Head circumference z-score is a measure of relative head circumference adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. Head circumference was collected only for participants of less than or equal to (\<=) 36 months of age at the time of measurement.
Time frame: Baseline, Week 28
Population: Safety analysis population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard of Care | Change From Baseline in Head Circumference Z-score at Week 28 | -0.014 Z-score |
Secondary
Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
The mean duration of the PN/IV infusions in hours, on the days when PN/IV was administered was reported.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | -1.48 Hours per day (hour/day) | Standard Deviation 3.59 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | -2.47 Hours per day (hour/day) | Standard Deviation 2.73 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | -3.03 Hours per day (hour/day) | Standard Deviation 3.84 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | -1.79 Hours per day (hour/day) | Standard Deviation 3.52 |
| Standard of Care | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Participant Diary | -0.21 Hours per day (hour/day) | Standard Deviation 0.69 |
| Standard of Care | Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | Investigator Prescribed | 0.11 Hours per day (hour/day) | Standard Deviation 0.33 |
Secondary
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24
Change in PN/IV caloric intake was reported based on the participant diary and the investigator prescribed data.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Participant Diary | -14.92 Kilocalories per kilogram per day | Standard Deviation 8.29 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Investigator Prescribed | -11.76 Kilocalories per kilogram per day | Standard Deviation 10.46 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Participant Diary | -18.99 Kilocalories per kilogram per day | Standard Deviation 14.28 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Investigator Prescribed | -18.51 Kilocalories per kilogram per day | Standard Deviation 13.22 |
| Standard of Care | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Participant Diary | -0.46 Kilocalories per kilogram per day | Standard Deviation 4.95 |
| Standard of Care | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24 | Investigator Prescribed | -0.27 Kilocalories per kilogram per day | Standard Deviation 2.73 |
Secondary
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24
Change in PN/IV volume was reported based on the participant diary and the investigator prescribed data.
Time frame: Baseline, Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | -16.16 Milliliters per kilogram per day | Standard Deviation 10.52 |
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | -11.28 Milliliters per kilogram per day | Standard Deviation 15.51 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | -23.30 Milliliters per kilogram per day | Standard Deviation 17.5 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | -22.13 Milliliters per kilogram per day | Standard Deviation 17.92 |
| Standard of Care | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Participant Diary | -6.03 Milliliters per kilogram per day | Standard Deviation 4.55 |
| Standard of Care | Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24 | Investigator Prescribed | -5.84 Milliliters per kilogram per day | Standard Deviation 9.8 |
Secondary
Change From Baseline in Participants' Stool Consistency at Week 28
Stool consistency was assessed by typical stool form based on Bristol Stool Form Scale: 1 - Separate hard lumps, hard to pass, 2 - Sausage-shaped, but lumpy, 3 - Like a sausage but with cracks on the surface, 4 - Like a sausage or snake, smooth and soft, 5 - Soft blobs with clear-cut edges, 6 - Fluffy pieces with ragged edges, a mushy stool, 7 - Watery, no solid pieces, entirely liquid.
Time frame: Baseline, Week 28
Population: Safety analysis population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Participants' Stool Consistency at Week 28 | -1.3 Score on a scale | Standard Deviation 1.77 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Participants' Stool Consistency at Week 28 | -1.4 Score on a scale | Standard Deviation 1.38 |
| Standard of Care | Change From Baseline in Participants' Stool Consistency at Week 28 | -3.3 Score on a scale | Standard Deviation 0.35 |
Secondary
Change From Baseline in Plasma Citrulline Levels at Week 24
Plasma citrulline level was reported.
Time frame: Baseline, Week 24
Population: ITT population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Baseline in Plasma Citrulline Levels at Week 24 | 7.7 Micromoles per liter | Standard Deviation 8.5 |
| 0.05 mg/kg/Day Teduglutide | Change From Baseline in Plasma Citrulline Levels at Week 24 | 12.0 Micromoles per liter | Standard Deviation 12 |
| Standard of Care | Change From Baseline in Plasma Citrulline Levels at Week 24 | 0.1 Micromoles per liter | Standard Deviation 7.79 |
Secondary
Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28
Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported.
Time frame: Week 24, Week 28
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Participant Diary | -1.07 Kilocalorie per kilogram per day | Standard Deviation 4.36 |
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Investigator Prescribed | 1.28 Kilocalorie per kilogram per day | Standard Deviation 4.3 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Investigator Prescribed | -0.11 Kilocalorie per kilogram per day | Standard Deviation 3.77 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Participant Diary | -0.14 Kilocalorie per kilogram per day | Standard Deviation 7.73 |
| Standard of Care | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Participant Diary | -0.42 Kilocalorie per kilogram per day | Standard Deviation 6.13 |
| Standard of Care | Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28 | Investigator Prescribed | 0.45 Kilocalorie per kilogram per day | Standard Deviation 0.64 |
Secondary
Change From Week 24 in Enteral Nutrition Volume at Week 28
Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported.
Time frame: Week 24, Week 28
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Participant Diary | -0.68 Milliliter per kilogram per day | Standard Deviation 3.86 |
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Investigator Prescribed | 1.67 Milliliter per kilogram per day | Standard Deviation 5.73 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Participant Diary | 1.38 Milliliter per kilogram per day | Standard Deviation 8.41 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Investigator Prescribed | 0.68 Milliliter per kilogram per day | Standard Deviation 6.65 |
| Standard of Care | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Participant Diary | -0.75 Milliliter per kilogram per day | Standard Deviation 6.78 |
| Standard of Care | Change From Week 24 in Enteral Nutrition Volume at Week 28 | Investigator Prescribed | 0.39 Milliliter per kilogram per day | Standard Deviation 0.57 |
Secondary
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28
Change in PN/IV caloric intake was reported.
Time frame: Week 24, Week 28
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Participant Diary | 0.88 Kilocalorie per kilogram per day | Standard Deviation 2.94 |
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Investigator Prescribed | 0.55 Kilocalorie per kilogram per day | Standard Deviation 3.42 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Participant Diary | -0.91 Kilocalorie per kilogram per day | Standard Deviation 7.14 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Investigator Prescribed | 0.08 Kilocalorie per kilogram per day | Standard Deviation 6.13 |
| Standard of Care | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Participant Diary | -4.21 Kilocalorie per kilogram per day | Standard Deviation 10.3 |
| Standard of Care | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28 | Investigator Prescribed | -4.34 Kilocalorie per kilogram per day | Standard Deviation 11.22 |
Secondary
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28
Change in PN/IV volume was reported.
Time frame: Week 24, Week 28
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Participant Diary | 2.63 Milliliter per kilogram per day | Standard Deviation 7.8 |
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Investigator Prescribed | 2.13 Milliliter per kilogram per day | Standard Deviation 6.95 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Participant Diary | 1.52 Milliliter per kilogram per day | Standard Deviation 12.68 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Investigator Prescribed | -0.35 Milliliter per kilogram per day | Standard Deviation 5.96 |
| Standard of Care | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Participant Diary | -2.99 Milliliter per kilogram per day | Standard Deviation 4.94 |
| Standard of Care | Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28 | Investigator Prescribed | -0.91 Milliliter per kilogram per day | Standard Deviation 2.18 |
Secondary
Change From Week 24 in Plasma Citrulline Levels at Week 28
Change in plasma citrulline level was reported.
Time frame: Week 24, Week 28
Population: ITT population with number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Change From Week 24 in Plasma Citrulline Levels at Week 28 | -6.0 Micromoles per liter | Standard Deviation 9.26 |
| 0.05 mg/kg/Day Teduglutide | Change From Week 24 in Plasma Citrulline Levels at Week 28 | -9.5 Micromoles per liter | Standard Deviation 10.33 |
| Standard of Care | Change From Week 24 in Plasma Citrulline Levels at Week 28 | 1.8 Micromoles per liter | Standard Deviation 6.48 |
Secondary
Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
A participant was considered to have achieved independence from PN/IV support (completely weaned off PN/IV) if the investigator prescribed no PN/IV at EOT and there was no use of PN/IV recorded in the participant diary during the week prior to EOT.
Time frame: Week 24
Population: ITT population included all enrolled participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | 2 Participants |
| 0.05 mg/kg/Day Teduglutide | Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | 3 Participants |
| Standard of Care | Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24 | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or worsened on or after the date of first dose for treatment groups and those that started or worsened on or after the baseline visit for standard of care group.
Time frame: From start of study treatment up to 28 weeks
Population: Safety analysis population included all participants who received at least 1 dose of teduglutide and had undergone at least 1 post-baseline safety assessment in teduglutide treatment group or participants who had undergone at least 1 post-baseline safety assessment in standard of care treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.025 mg/kg/Day Teduglutide | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 24 Participants |
| 0.05 mg/kg/Day Teduglutide | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 25 Participants |
| Standard of Care | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |