Clinical trial NCT03571516: Safety, Efficacy and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: Short bowel syndrome
Teduglutide
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-06-27
Enrollment: 10
Sex: ALL
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.
* 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.

Primary outcomes:
measure: 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)
timeFrame: Baseline, EOT/ET (up to Week 24)
Secondary outcomes:
measure: 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)
timeFrame: Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study treatment up to end of study (EOS) (up to Week 28)
measure: Change From Baseline in Body Weight Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Length Z-Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Head Circumference Z-Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Weight-for-Length Z-Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Average Total Urine Output at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fecal Output at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With Positive Specific Antibodies to Teduglutide
timeFrame: Baseline, EOS (up to week 28)
measure: 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)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24
timeFrame: Week 24
measure: Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS)
timeFrame: EOS (up to Week 28)
measure: Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: 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)
timeFrame: Baseline, EOT/ET (up to Week 24)
measure: 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)
timeFrame: Baseline, EOT/ET (up to Week 24)
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital des Enfants
state: Gironde
city: Lille
country: France
facility: Hopital Jeanne de Flandre - CHRU Lille
state: Nord
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: Greater London
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: Greater Manchester
city: Liverpool
country: United Kingdom
facility: Alder Hey Childrens Hospital
state: Merseyside
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: