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

NCT02682381 | Completed Phase 3 Results DMC

• 1 other identifier: TED-C14-006
• Study Type: interventional
• Target: 59
• Locations: 7 countries
• Sites: 27

Brief Summary

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.

Conditions

Short Bowel Syndrome

Keywords

Teduglutide; pediatric; GLP-2; parenteral support; Short Bowel Syndrome; short gut syndrome; short gut; SBS; parenteral nutrition

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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

  Week 24

• Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24

  Baseline, Week 24

• Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24

  Baseline, Week 24

• Change From Baseline in Plasma Citrulline Levels at Week 24

  Baseline, Week 24

Study Arms (3)

0.025 mg/kg/day Teduglutide

EXPERIMENTAL

0.025 milligrams per kilogram per day (mg/kg/day) of teduglutide for 24 weeks.

Drug: Teduglutide 0.025 mg/kg

0.05 mg/kg/day Teduglutide

EXPERIMENTAL

0.05 mg/kg/day of teduglutide for 24 weeks.

Drug: Teduglutide 0.05mg/kg

Standard of care

ACTIVE COMPARATOR

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

Interventions

Teduglutide 0.05mg/kg DRUG

0.05 mg/kg

0.05 mg/kg/day Teduglutide

Teduglutide 0.025 mg/kg DRUG

0.025 mg/kg

0.025 mg/kg/day Teduglutide

Standard of Care OTHER

Observational cohort for the 24-week treatment period and 4 week follow-up.

Standard of care

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed consent by a parent or guardian or emancipated minor prior to any study-related procedures
• When applicable, an informed assent by the subject (as deemed appropriate by the Ethics Committee/Institutional Review Board) prior to any study-related procedures
• Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis)
• Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs prior to screening
• 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.
• 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

You may not qualify if:

• Subjects who are not expected to be able to advance oral or tube feeding regimens
• Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening
• Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support
• Unstable absorption due to cystic fibrosis or known DNA abnormalities
• 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.
• Evidence of clinically significant obstruction on upper GI series done within 6 months prior to screening.
• 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).
• 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.
• 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.
• Pregnant or lactating female subjects (in the teduglutide treatment arm only).
• 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.
• Previous use of teduglutide or native/synthetic glucagon-like peptide-2 (GLP-2)
• Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening
• Previous use of octreotide, or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening
• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (27)

Children's Hospital Los Angeles - RHU

Los Angeles, California, 90027, United States

Location

UCLA Dept. of Medicine

Los Angeles, California, 90095, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Georgetown Children's Research Network

Washington D.C., District of Columbia, 20007, United States

Location

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

The Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Children's Hospital GI Nutrition

New York, New York, 10032, United States

Location

Montefiore Medical Center Child Spc

The Bronx, New York, 10467, United States

Location

Duke Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic Pediatric Specialists

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Walter C. Mackenzie Health Science Center

Edmonton, Alberta, T6G 1C9, Canada

Location

British Columbia Children's & Women's Hospital Center

Vancouver, British Columbia, V6H 3V4, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Helsingin yliopistollinen keskussairaala

Helsinki, 00290, Finland

Location

Universitaetsklinikum Tuebingen

Tübingen, Baden Wuertternberg, 72076, Germany

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Great Ormond Street Hospital for Children

London, Greater London, WC1N 3JH, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Related Publications (1)

• Fifi A, Raphael BP, Terreri B, Uddin S, Kaufman SS. Effects of Teduglutide on Diarrhea in Pediatric Patients with Short Bowel Syndrome-Associated Intestinal Failure. J Pediatr Gastroenterol Nutr. 2023 Nov 1;77(5):666-671. doi: 10.1097/MPG.0000000000003922. Epub 2023 Aug 22.

  PMID: 37889619 DERIVED

MeSH Terms

Conditions

Short Bowel Syndrome; Hyperphagia

Interventions

teduglutide; Standard of Care

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2016
• First Posted: February 15, 2016
• Study Start: June 23, 2016
• Primary Completion: August 18, 2017
• Study Completion: August 18, 2017
• Last Updated: June 9, 2021
• Results First Posted: October 16, 2018

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

FI (1); BE (1); GB (2); US (18); CA (3); DE (1); IT (1)