Short Bowel Syndrome Research Study for Children Up To 17 Years of Age on Parenteral Nutrition

A 24-Week Double-blind, Safety, Efficacy, and Pharmacodynamic Study Investigating Two Doses of Teduglutide in Pediatric Subjects Through 17 Years of Age With Short Bowel Syndrome Who Are Dependent on Parenteral Support

Teduglutide is approved for treatment of adults with short bowel syndrome (SBS). The purpose of this study is to evaluate the safety and efficacy of teduglutide in children up to the age of 17 with SBS who are dependent on parenteral support. Subjects may choose whether to receive the study drug or to participate in a standard-of-care arm. All participants who complete the study may be eligible to receive the study drug in a long-term extension study.

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Teduglutide 0.025 mg/kg; Drug: Teduglutide 0.05mg/kg; Other: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Walter C. Mackenzie Health Science Center
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's & Women's Hospital Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Finland
  • Helsinki, Finland, 00290
    • Helsingin Yliopistollinen Keskussairaala
• Germany
  • Baden Wuertternberg
    • Tuebingen, Baden Wuertternberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
• Italy
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesu
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - RHU
    • Los Angeles, California, United States, 90095
      • Ucla Dept. Of Medicine
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Children's Research Network
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • The Nebraska Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center Child Spc
    • New York, New York, United States, 10032
      • Children's Hospital GI Nutrition
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Pediatric Specialists
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent by a parent or guardian or emancipated minor prior to any study-related procedures
2. When applicable, an informed assent by the subject (as deemed appropriate by the Ethics Committee/Institutional Review Board) prior to any study-related procedures
3. Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis)
4. Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs prior to screening
5. Stable PN/IV support, defined as inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 3 months prior to and during screening, as assessed by the investigator.
6. Sexually active female subjects of child-bearing potential (in the teduglutide treatment arm only) must use medically acceptable methods of birth control during and 4 weeks after the treatment period

Exclusion Criteria:

1. Subjects who are not expected to be able to advance oral or tube feeding regimens
2. Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening
3. Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support
4. Unstable absorption due to cystic fibrosis or known DNA abnormalities
5. 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 parenteral support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding.
6. Evidence of clinically significant obstruction on upper GI series done within 6 months prior to screening.
7. Major GI surgical intervention including significant intestinal resection within 3 months prior to the screening visit (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections ≤ 10 cm, or endoscopic procedure is allowed).
8. Unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of subjects who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation.
9. History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ non aggressive and surgically resected cancer.
10. Pregnant or lactating female subjects (in the teduglutide treatment arm only).
11. Participation in a clinical study using an experimental drug (other than glutamine or Omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to screening, and for the duration of the study.
12. Previous use of teduglutide or native/synthetic glucagon-like peptide-2 (GLP-2)
13. Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening
14. Previous use of octreotide, or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening
15. Subjects with active Crohn's disease who had been treated with biological therapy (eg, antitumor necrosis factor [anti-TNF]) within the 6 months prior to the screening visit
16. Subjects with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening
17. More than 3 SBS-related or PN-related hospital admissions (eg, documented infection-related catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to the screening visit
18. Any major unscheduled hospital admission which affects parenteral support requirements within 1 month prior to or during screening, excluding uncomplicated treatment of bacteremia, central line replacement/repair, or issues of similar magnitude in an otherwise stable subject
19. Body weight < 10 kg at the screening and baseline visits

20. Signs of active severe or unstable, clinically significant hepatic impairment during the screening period, as indicated by any of the following laboratory test results :

    1. Total bilirubin (TBL) ≥ 2 x upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST) ≥ 7x ULN

    3. Alanine aminotransferase (ALT) ≥ 7x ULN

       For subjects with Gilbert's disease:

    4. Indirect (unconjugated) bilirubin ≥ 2x ULN
21. Signs of known continuous active or unstable, clinically significant renal dysfunction shown by results of an estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m2.
22. Parent(s) and/or subjects who are not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements
23. Unstable, clinically significant active, untreated pancreatic or biliary disease
24. Any condition, disease, illness, or circumstance that in the investigator's opinion puts the subject at any undue risk, prevents completion of the study, or interferes with analysis of the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.025 mg/kg/day Teduglutide; 0.025 milligrams per kilogram per day (mg/kg/day) of teduglutide for 24 weeks.	Drug: Teduglutide 0.025 mg/kg; 0.025 mg/kg
Experimental: 0.05 mg/kg/day Teduglutide; 0.05 mg/kg/day of teduglutide for 24 weeks.	Drug: Teduglutide 0.05mg/kg; 0.05 mg/kg
Active Comparator: Standard of care; Observational cohort for the 24-week treatment period and 4 week follow-up. The subjects in the standard of care group will follow the same visit schedule as the randomized subjects.	Other: Standard of Care; Observational cohort for the 24-week treatment period and 4 week follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved at Least a 20 Percent (%) Reduction in Weight-Normalized Average Daily Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24	Reduction in weight-normalized PN/IV volume was performed using both participant diary and investigator prescribed data. Number of participants who achieved at least a 20% reduction in weight-normalized PN/IV volume between the baseline and week 24/EOT visit were reported.	Baseline through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or worsened on or after the date of first dose for treatment groups and those that started or worsened on or after the baseline visit for standard of care group.	From start of study treatment up to 28 weeks
Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	A participant was considered to have achieved independence from PN/IV support (completely weaned off PN/IV) if the investigator prescribed no PN/IV at EOT and there was no use of PN/IV recorded in the participant diary during the week prior to EOT.	Week 24
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24	Change in PN/IV volume was reported based on the participant diary and the investigator prescribed data.	Baseline, Week 24
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24	Change in PN/IV caloric intake was reported based on the participant diary and the investigator prescribed data.	Baseline, Week 24
Change From Baseline in Plasma Citrulline Levels at Week 24	Plasma citrulline level was reported.	Baseline, Week 24
Change From Baseline in Enteral Nutrition Volume at Week 24	Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported.	Baseline, Week 24
Change From Baseline in Enteral Nutrition Caloric Intake at Week 24	Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported.	Baseline, Week 24
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28	Change in PN/IV volume was reported.	Week 24, Week 28
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28	Change in PN/IV caloric intake was reported.	Week 24, Week 28
Change From Week 24 in Plasma Citrulline Levels at Week 28	Change in plasma citrulline level was reported.	Week 24, Week 28
Change From Week 24 in Enteral Nutrition Volume at Week 28	Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition volume was reported.	Week 24, Week 28
Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28	Enteral nutrition was defined as specialized formula taken orally or by tube feeding, and excluded table foods and other fluids. Change in enteral nutrition caloric intake was reported.	Week 24, Week 28
Change From Baseline in Body Weight Z-score at Week 28	Body weight z-score is a measure of relative weight adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline, Week 28
Change From Baseline in Body Height Z-score at Week 28	Body height z-score is a measure of relative height adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline, Week 28
Change From Baseline in Head Circumference Z-score at Week 28	Head circumference z-score is a measure of relative head circumference adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. Head circumference was collected only for participants of less than or equal to (<=) 36 months of age at the time of measurement.	Baseline, Week 28
Change From Baseline in Body Mass Index (BMI) Z-score at Week 28	BMI z-score is a measure of relative BMI adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline, Week 28
Change From Baseline in Participants' Stool Consistency at Week 28	Stool consistency was assessed by typical stool form based on Bristol Stool Form Scale: 1 - Separate hard lumps, hard to pass, 2 - Sausage-shaped, but lumpy, 3 - Like a sausage but with cracks on the surface, 4 - Like a sausage or snake, smooth and soft, 5 - Soft blobs with clear-cut edges, 6 - Fluffy pieces with ragged edges, a mushy stool, 7 - Watery, no solid pieces, entirely liquid.	Baseline, Week 28
Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	The mean duration of the PN/IV infusions in hours, on the days when PN/IV was administered was reported.	Baseline, Week 24
Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	The number of days per week of PN/IV infusions were reported.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2016
• Primary Completion (Actual): August 18, 2017
• Study Completion (Actual): August 18, 2017

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimate): February 15, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: pediatric; parenteral nutrition; Short Bowel Syndrome; SBS; Teduglutide; GLP-2; parenteral support; short gut syndrome; short gut
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Radiation-Protective Agents; Teduglutide
• Other Study ID Numbers: TED-C14-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)