Long-term Safety and Efficacy Study of Teduglutide in Pediatric Participants With Short Bowel Syndrome (SBS)

Study Overview
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Brief Summary
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This study will follow participants who completed the TED-C14-006 study. The purpose of this study is to evaluate the long-term safety and efficacy of teduglutide in pediatric participants with Short Bowel Syndrome (SBS). This study will also offer teduglutide treatment to eligible participants, regardless of treatment received in TED-C14-006 or SHP633-301.

Official Title
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A Prospective, Open-label, Long-term Safety and Efficacy Study of Teduglutide in Pediatric Patients With Short Bowel Syndrome Who Completed TED-C14-006 or SHP633-301

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: TED
* Other: SOC
* Device: Syringe
* Device: Needle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant provides written informed consent (participant, parent or legal guardian and, as appropriate, informed assent) to participate in the study before completing any study-related procedures. Participant completed the TED-C14-006 or SHP633-301 studies (including participants in the standard of care treatment arms). Participants are considered to have completed SHP633-301 if they completed study assessments through week 24. Participant understands and is willing and able to fully adhere to study requirements as defined in this protocol. Exclusion Criteria: 1. There are no exclusion criteria for this study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of care (SOC) treatment +/- teduglutide (TED)<br>Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment. | Drug: TED<br>* 0.05 mg/kg SC injection once daily.<br>Other: SOC<br>* Standard safety assessments and adjustments in nutritional support.<br>Device: Syringe<br>* Teduglutide will be administered using syringe.<br>Device: Needle<br>* Teduglutide will be administered using needle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does 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 of teduglutide for participants in the TED/TED, TED/NTT, and NTT/TED treatment groups, or after the core study baseline visit for participants in the NTT/NTT group. | From start of study drug administration up to follow-up (up to 46 months) | 
| Change From Baseline in Average Total Urine Output at End of Treatment (EOT) of Last Cycle During Teduglutide Treatment | Average total urine output was recorded over a 48-hour period of parental support (PS) stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily urine output milliliter per kilogram per day (mL/kg/day) was calculated as: Total urine output over 48 hours / 2) / body weight (kilogram [kg]) where total urine output was calculated as the sum of the urine output in milliliter (mL) and the urine-only diaper weights in gram (g) (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF). | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Average Total Urine Output at Last Visit During Non-Teduglutide Treatment (NT) | Average total urine output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. Average daily urine output mL/kg/day was calculated as: (Total urine output over 48 hours/2) / body weight (kg) where total urine output was calculated as the sum of the urine output in mL and the urine-only diaper weights in gram (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF). | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Average Number of Stools Per Day at EOT of Last Cycle During Teduglutide Treatment | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2). | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Average Number of Stools Per Day at Last Visit During Non-Teduglutide Treatment (NT) | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2). | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at EOT of Last Cycle During Teduglutide Treatment | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day [g/kg/day]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day). | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at Last Visit During Non-Teduglutide Treatment (NT) | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day [g/kg/day]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day). | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Average Total Ostomy Output at EOT of Last Cycle During Teduglutide Treatment | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day (mL/kg/day). | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Average Total Ostomy Output at Last Visit During Non-Teduglutide Treatment (NT) | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day. | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Average Bristol Stool Form Score at EOT of Last Cycle During Teduglutide Treatment | Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily fecal output was summarized the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). 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. | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Average Bristol Stool Form Score at Last Visit During Non-Teduglutide Treatment (NT) | Fecal output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized separately the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). 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. | Baseline, Last visit in NT (up to Month 39) | 
| Number of Participants With Positive Specific Antibodies at End of Study (EOS) | Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. | At EOS (up to 46 months) | 
| Change From Baseline in Body Weight Z-score at EOT of Last Cycle During Teduglutide Treatment | Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Body Weight Z-score at Last Visit During Non-Teduglutide Treatment (NT) | Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Height Z-score at EOT of Last Cycle During Teduglutide Treatment | Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Height Z-score at Last Visit During Non-Teduglutide Treatment | Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Head Circumference Z-score at EOT of Last Cycle During Teduglutide Treatment | Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Head Circumference Z-score at Last Visit During Non-Teduglutide Treatment (NT) | Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, Last visit in NT (up to Month 39) | 
| Change From Baseline in Body Mass Index (BMI) Z-score at EOT of Last Cycle During Teduglutide Treatment | BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Body Mass Index (BMI) Z-score at Last Visit During Non-Teduglutide Treatment (NT) | BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age >= 2 years old) and World Health Organization (age < 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline, Last visit in NT (up to Month 39) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Diary Parenteral Support (PS) Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment | Number of participants who achieved at least 20%, 50%, and 75% reduction from baseline in diary PS volume at EOT of last cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Prescribed PS Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment | Number of participants who achieved at least 20%, 50%, and 75% reduction from baseline in prescribed PS volume at EOT of east cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in diary PS volume at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in diary PS volume at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Prescribed PS Volume at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in prescribed PS volume at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Prescribed PS Volume at EOT of Each Cycle During Teduglutide Treatment | Percent Change from baseline in prescribed PS volume at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Diary PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in diary PS caloric intake at EOT of each cycle during teduglutide treatment was reported. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Diary PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in diary PS Caloric intake at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Prescribed PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in prescribed PS caloric intake at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Prescribed PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in prescribed PS caloric intake at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Number of Participants Who Achieved 100% Reduction in Complete Weaning of PS Volume at EOT of Each Cycle During Teduglutide Treatment | Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT of each cycle during teduglutide treatment was reported. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Hours Per Day of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in hours per day of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of diary PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit). | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Hours Per Day of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in hours per day of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of diary PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit). | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Hours Per Day of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in hours per day of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of dairy PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit). | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Hours Per Day of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in hours per day of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of dairy PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit). | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Days Per Week of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in days per week of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of diary PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) * 7. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Days Per Week of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in days per week of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of diary PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) * 7. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Change From Baseline in Days Per Week of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment | Change from baseline in days per week of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of dairy PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) * 7 | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Days Per Week of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment | Percent change from baseline in days per week of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of dairy PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) * 7. | Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks) |