Safety, Efficacy and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, efficacy/pharmacodynamics (PD) and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral (PN) support.

Official Title
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A Randomized, Open-label, 24-Week Safety, Efficacy, and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome Who Are Dependent on Parenteral Support

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Teduglutide
* Other: Standard Medical Therapy
* Device: Syringe
* Device: Needle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent by the parent or legal guardian. Male or female infant 4 to 12 months corrected gestational age at screening. Weight at least 5 kilogram (kg) and weight-for-length Z-score greater than -2 at screening and baseline. Short bowel syndrome with dependence on parenteral support to provide at least 50% of fluid or caloric needs. Stable PN requirements for at least 1 month prior to screening, defined as a less than or equal to (<=) 10% change in the weight-normalized PN total fluid and caloric intake, despite attempts to wean PN, not withstanding transient instability for events such as sepsis or interruption of central venous access. Parent or legal guardian understands and is willing and able to fully adhere to study requirements as defined in this protocol. Exclusion Criteria: Previous treatment with teduglutide. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc. 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 PN support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding. Inability to advance oral or enteral feeding due to lack of access to the gut, such as oral aversion in the absence of a feeding tube. Intestinal obstruction or clinically significant intestinal stenosis. Major gastrointestinal surgical intervention, such as serial transverse enteroplasty or major intestinal resection or anastomosis, within 3 months prior to screening or planned during the study period. Unstable cardiac disease. Renal dysfunction, defined as estimated glomerular filtration rate less than (<) 50 milliliter per minute (mL/min) per 1.73 square meter (m^2). Biliary obstruction, stenosis, or malformation. Clinically significant pancreatic disease. Severe hepatic dysfunction or portal hypertension, defined by at least 2 of the following parameters: International normalized ratio (INR) greater than (>) 1.5 not corrected with PN vitamin K Platelet count <100×10^3/ microliter (mcL) due to portal hypertension Presence of clinically significant gastric or esophageal varices Documented cirrhosis Persistent cholestasis defined as conjugated bilirubin >4 milligram per deciliter (mg/dL) (>68 micromoles per liter [mcmol/L]) over a 2 week period. More than 3 serious complications of intestinal failure (example [e.g.], catheter-associated bloodstream infections, interruption of nutrition due to feeding intolerance, catheter-associated thrombosis, severe fluid or electrolyte disturbances) within 1 month prior to or during screening. A history of cancer or a known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of gastrointestinal cancer (including hepatobiliary and pancreatic cancers). Concurrent treatment with glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); insulin-like growth factor-1 (IGF-1); growth hormone, somatostatin, or analogs of these hormones; or glutamine. Participation in a clinical study using an experimental drug within 3 months or 5.5 half-lives of the experimental drug, whichever is longer. Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients. Any condition, disease, illness, or circumstance that, in the investigator's opinion, puts the participant at any undue risk, prevents completion of the study, or interferes with analysis of the study results.

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 12 Months

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teduglutide<br>Participants will receive 0.05 milligram per kilogram (mg/kg) subcutaneous (SC) injection of teduglutide into abdomen or into either the thigh or arm once daily (QD) in addition to standard medical therapy for 24 weeks. | Drug: Teduglutide<br>* SC injection of 0.05 mg/kg teduglutide will be administered QD into abdomen or into either the thigh or arm for 24 weeks.<br>Other: Standard Medical Therapy<br>* Standard medical therapy will be administered for 24 weeks.<br>Device: Syringe<br>* Teduglutide will be administered using syringe (510k number: K980987).<br>Device: Needle<br>* Teduglutide will be administered using needle (510k number: K021475).<br>|
| Other: Standard of Care (SOC)<br>Participants will receive standard medical therapy for 24 weeks. | Other: Standard Medical Therapy<br>* Standard medical therapy will be administered for 24 weeks.<br>Device: Syringe<br>* Teduglutide will be administered using syringe (510k number: K980987).<br>Device: Needle<br>* Teduglutide will be administered using needle (510k number: K021475).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Mean plasma concentration of teduglutide was reported. | Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7 | 
| 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 are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product. | From start of study treatment up to end of study (EOS) (up to Week 28) | 
| Change From Baseline in Body Weight Z-score at Week 24 | 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. 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 Z-score at Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Length Z-Score at Week 24 | Length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. 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 length Z-score at Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Head Circumference Z-Score at Week 24 | 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. 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 head circumference Z-score at Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Weight-for-Length Z-Score at Week 24 | Weight-for-length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. 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 weight-for-length Z-score at Week 24 was reported. | Baseline, Week 24 | 
| Change From Baseline in Average Total Urine Output at Week 24 | Average total urine output was recorded over a 48-hour period of nutritional stability at Week 24 was reported. Here, milliliter per kilogram per day is abbreviated as mL/kg/day. | Baseline, Week 24 | 
| Change From Baseline in Fecal Output at Week 24 | Change from baseline in the fecal output (average number of stools per day) at Week 24 was reported. | Baseline, Week 24 | 
| Number of Participants With Positive Specific Antibodies to Teduglutide | Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. | Baseline, EOS (up to week 28) | 
| Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24 | Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at Week 24 were reported. | Week 24 | 
| Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS) | Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at EOS (up to Week 28) were reported. | EOS (up to Week 28) | 
| Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Percent change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). | Baseline, EOT/ET (up to Week 24) | 
| Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Percent change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Percent change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Percent change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Number of participants who achieved at least 20% increase from baseline in weight-normalized EN volume at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 
| Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Number of participants who achieved at least 20% increase from baseline in weight-normalized EN caloric intake at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. | Baseline, EOT/ET (up to Week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short bowel syndrome, Teduglutide