Long-term Study of Teduglutide in Pediatric Subjects With Short Bowel Syndrome Who Completed the TED-C13-003 Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of teduglutide treatment of children with short bowel syndrome (SBS) who completed the TED-C13-003 study over a long-term period. It will evaluate how these children fared after the TED-C13-003 study ended. This study will also offer teduglutide treatment to eligible subjects, regardless of treatment received in TED-C13-003.

Official Title
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A Retrospective and Prospective, Open-label, Long-term Safety and Efficacy Study of Teduglutide in Pediatric Subjects With Short Bowel Syndrome Who Completed TED-C13-003

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Teduglutide
* Other: SOC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject provides written informed consent (subject, parent or legal guardian and, as appropriate, subject informed assent) to participate in the study before completing any study-related procedures. Subject completed the TED-C13-003 study (including subjects in the standard of care treatment arm). Subject understands and is willing and able to fully adhere to study requirements as defined in this protocol. Exclusion Criteria: 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<br>TED 0.05mg/kg subcutaneous injections once daily as needed in addition to SOC treatment | Drug: Teduglutide<br>* 0.05mg/kg<br>Other: SOC<br>* Standard safety assessments and adjustments in nutritional support will be provided for all subjects throughout the study, including any teduglutide treatment periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) in Retrospective Observation Period | An 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. A SAE was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, was an important medical event. Number of participants with AEs, related AEs, serious adverse events (SAEs) and related SAEs of retrospective observation period were reported. | From end of the core study (TED-C13-003 [NCT01952080]) up to the beginning of the prospective period (up to Week 168) | 
| Change From Baseline in Height for Age Z-score up to Week 168 of Retrospective Observation Period | Height was measured using age 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 greater than or equal to [>=] 2 years old) and World Health Organization (age less than [<] 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. Change from baseline in height for age Z-score up to Week 168 of retrospective observation period was reported. Data for this outcome was not planned to be collected and analyzed in retrospective TED/TED group. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]) up to the beginning of the prospective period (up to Week 168) | 
| Change From Baseline in Body Weight for Age Z-score up to Week 168 of Retrospective Observation Period | Body weight was measured using age 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. Change from baseline in body weight for age Z-score up to Week 168 was reported. Data for this outcome was not planned to be collected and analyzed in retrospective TED/TED group. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]) up to the beginning of the prospective period (up to Week 168) | 
| Change From Baseline in Body Mass Index (BMI) for Age Z-score up to Week 168 of Retrospective Observation Period | BMI Z-score was calculated by using the retrospective 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. Change from baseline in height for age Z-score up to Week 168 of retrospective observation period was reported. Data for this outcome was not planned to be collected and analyzed in retrospective TED/TED group. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]) up to the beginning of the prospective period (up to Week 168) | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Prospective Study Period | TEAEs are defined as AEs that started or worsened on or after the first dose of teduglutide treatment in the core study. A SAE was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, was an important medical event. AESI was an TEAE or TESAE of scientific and medical concern specific to the sponsor's product or program and for which ongoing monitoring and immediate notification by the investigator to the sponsor. Number of participants With TEAEs, treatment -emergent serious adverse events (TESAEs) and adverse events of special interest (AESI) of Prospective study period were reported. | From the beginning of the prospective study period to End of Study (EOS) (up to Week 144) | 
| Change From Baseline in Height for Age Z-score up to Cycle 6 Week 12 During the End of Teduglutide Treatment Period of Prospective Study Period | Height was measured using age 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. Change from baseline in height for age Z-score up to Cycle 6 Week 12 during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Cycle 6 Week 12 | 
| Change From Baseline in Body Weight for Age Z-score up to Cycle 6 Week 24 During the End of Teduglutide Treatment Period of Prospective Study Period | Body weight was measured using age 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. Change from baseline in body weight for age Z-score up to Cycle 6 Week 24 during the end of teduglutide treatment period of prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Cycle 6 Week 24 | 
| Change From Baseline in BMI for Age Z-score up to Cycle 6 Week 12 During the End of Teduglutide Treatment Period of Prospective Study Period | 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. Change from baseline in BMI for age Z-score up to Cycle 6 Week 12 during the end of teduglutide treatment period of prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Cycle 6 Week 12 | 
| Average Total 48-Hour Urine Output up to Cycle 6 Week 12 During the End of Teduglutide Treatment Period of Prospective Study Period | Average total urine output was calculated based on the daily data recorded in participants diaries over a 48-hour period of nutritional stability prior to each scheduled visit. Average total 48-Hour urine output up to Cycle 6 Week 12 during the end of teduglutide treatment period of prospective study period was reported. Here, mL/kg/day is abbreviated as milliliter per kilogram per day. | Baseline (from the beginning of the prospective study period) up to Cycle 6 Week 12 | 
| Average Total 48-Hour Urine Output up to Week 108 During the End of Non-Teduglutide Treatment (NTT) Period of Prospective Study Period | Average total urine output was calculated based on the daily data recorded in participants diaries over a 48-hour period of nutritional stability prior to each scheduled visit. Average total 48-Hour urine output up to Week 108 during the end of NTT period in prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Week 108 | 
| Average Number of Stools Per Day up to Cycle 6 Week 24 During the End of Teduglutide Treatment Period of Prospective Study Period | Average number of stools per day was calculated based on the daily data recorded in participants diaries over a 48-hour period of nutritional stability prior to each scheduled visit. Average number of stools per day up to cycle 6 week 24 during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Cycle 6 Week 24 | 
| Average Number of Stools Per Day up to Week 120 During the End of NTT Period of Prospective Study Period | Average number of stools per day was calculated based on the daily data recorded in participants diaries over a 48-hour period of nutritional stability prior to each scheduled visit. Average number of stools per day up to Week 120 during the end of NTT period in prospective study period was reported. | Baseline (from the beginning of the prospective study period) up to Week 120 | 
| Number of Participants With Positive Specific Antibodies at EOS During the End of Teduglutide Treatment Period of Prospective Study Period | Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. | From the beginning of the prospective study period, EOS (up to Week 156) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Number of participants achieved at least 20% reduction in PS volume at 12 weeks interval up to Week 156 in retrospective observation period was reported. | At Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Change From Baseline in PS Volume at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Change from baseline in PS volume at 12 weeks interval up to Week 156 in retrospective observation period was reported. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Percent Change From Baseline in PS Volume at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Percent change from baseline in PS volume at 12 weeks interval up to Week 156 of retrospective observation period was reported. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Change From Baseline in PS Caloric Intake at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Change from baseline in PS caloric intake at 12 weeks interval up to Week 156 of retrospective observation period was reported. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Percent Change From Baseline in PS Caloric Intake at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Percent change from baseline in PS caloric intake at 12 weeks interval up to Week 156 of retrospective observation period was reported. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Change From Baseline in Number of Hours Per Day of PS Usage at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Data for this outcome measure was not analyzed and collected because changes from baseline for prescribed hours per day were not collected at baseline in the core study. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]) up to Week 156 | 
| Percent Change From Baseline in Number of Hours Per Day of PS Usage at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Data for this outcome measure was not analyzed and collected because changes from baseline for prescribed hours per day were not collected at baseline in the core study. Hence, percent change was not assessed in this study. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]) up to Week 156 | 
| Change From Baseline in Number of Days Per Week of PS Usage at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Change from baseline in number of days per Week of PS usage at 12 weeks interval up to Week 156 in retrospective observation period was reported. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Percent Change From Baseline in Number of Days Per Week of PS Usage at 12 Weeks Interval up to Week 156 of Retrospective Observation Period | Percent change from baseline in number of days per Week of PS usage at 12 weeks interval up to Week 156 in retrospective observation period was reported. | Baseline (Baseline visit in the core study [TED-C13-003 (NCT01952080)]), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | 
| Number of Participants Who Achieved At Least 20, 50 and 75% Reduction in PS Volume at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Number of participants who achieved at least 20, 50 and 75% reduction in PS volume at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | At EOT of each Cycles 1 to 6 (up to Week 140) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 20 weeks) | 
| Change From Baseline in PS Volume at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Change from baseline in PS volume at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in PS Volume at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Percent change from baseline in PS volume at EOT of each cycle during the end of teduglutide treatment period in prospective study period. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Change From Baseline in PS Caloric Intake at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Change from baseline in PS caloric intake at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in PS Caloric Intake at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Percent change from baseline in PS caloric intake at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Number of Participants Who Achieved 100% Reduction in Complete Weaning of PS Volume at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | At EOT of each Cycles 1 to 6 (up to Week 144) (length of each Cycle 1 to 6 = 24 weeks) | 
| Change From Baseline in Number of Hours Per Day of PS Usage at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Change from baseline in number of hours per day of PS usage at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Number of Hours Per Day of PS Usage at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Percent change from baseline in number of hours per day of PS usage at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Change From Baseline in Number of Days Per Week of PS Usage at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Change from baseline in number of days per week of PS usage at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) | 
| Percent Change From Baseline in Number of Days Per Week of PS Usage at EOT of Each Cycle During the End of Teduglutide Treatment Period of Prospective Study Period | Percent change from baseline in number of days per week of PS usage at EOT of each cycle during the end of teduglutide treatment period in prospective study period was reported. | Baseline (from the beginning of the prospective study period), EOT of each Cycles 1 to 6 (up to Week 136) (length of each Cycle 1 to 5 = 24 weeks, length of Cycle 6 = 16 weeks) |