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
Overview
- Phase
- Phase 3
- Intervention
- Teduglutide
- Conditions
- Short Bowel Syndrome
- Sponsor
- Shire
- Enrollment
- 10
- Locations
- 8
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Teduglutide
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.
Intervention: Teduglutide
Teduglutide
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.
Intervention: Standard Medical Therapy
Teduglutide
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.
Intervention: Syringe
Teduglutide
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.
Intervention: Needle
Standard of Care (SOC)
Participants will receive standard medical therapy for 24 weeks.
Intervention: Standard Medical Therapy
Standard of Care (SOC)
Participants will receive standard medical therapy for 24 weeks.
Intervention: Syringe
Standard of Care (SOC)
Participants will receive standard medical therapy for 24 weeks.
Intervention: Needle
Outcomes
Primary Outcomes
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)
Time Frame: Baseline, EOT/ET (up to Week 24)
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.
Secondary Outcomes
- Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS)(EOS (up to Week 28))
- Change From Baseline in Length Z-Score at Week 24(Baseline, Week 24)
- Change From Baseline in Weight-for-Length Z-Score at Week 24(Baseline, Week 24)
- Change From Baseline in Fecal Output at Week 24(Baseline, Week 24)
- Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24(Week 24)
- Change From Baseline in Body Weight Z-score at Week 24(Baseline, Week 24)
- Change From Baseline in Average Total Urine Output at Week 24(Baseline, Week 24)
- Number of Participants With Positive Specific Antibodies to Teduglutide(Baseline, EOS (up to week 28))
- Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)(Baseline, EOT/ET (up to Week 24))
- 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)(Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7)
- Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)(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)(Baseline, EOT/ET (up to Week 24))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of study treatment up to end of study (EOS) (up to Week 28))
- Change From Baseline in Head Circumference Z-Score at Week 24(Baseline, Week 24)
- 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)(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)(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)(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)(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)(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)(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)(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)(Baseline, EOT/ET (up to Week 24))