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

Short Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03571516
• Other study ID #: SHP633-301
• Secondary ID: 2017-003606-40
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2018
• Est. completion date: September 24, 2020

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 24, 2020
• Est. primary completion date: September 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 12 Months

Eligibility

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:

1. International normalized ratio (INR) greater than (>) 1.5 not corrected with PN vitamin K

2. Platelet count <100×10^3/ microliter (mcL) due to portal hypertension

3. Presence of clinically significant gastric or esophageal varices

4. 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.

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Teduglutide
SC injection of 0.05 mg/kg teduglutide will be administered QD into abdomen or into either the thigh or arm for 24 weeks.

Other:
• Standard Medical Therapy
Standard medical therapy will be administered for 24 weeks.

Device:
• Syringe
Teduglutide will be administered using syringe (510k number: K980987).
• Needle
Teduglutide will be administered using needle (510k number: K021475).

Locations

Country	Name	City	State
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
France	Groupe Hospitalier Pellegrin - Hôpital des Enfants	Bordeaux	Gironde
France	Hopital Jeanne de Flandre - CHRU Lille	Lille	Nord
Italy	Ospedale Pediatrico Bambino Gesù	Roma
United Kingdom	Birmingham Children's Hospital	Birmingham	West Midlands
United Kingdom	Alder Hey Childrens Hospital	Liverpool	Merseyside
United Kingdom	Great Ormond Street Hospital for Children	London	Greater London
United Kingdom	Royal Manchester Children's Hospital	Manchester	Greater Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

Finland,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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