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

NCT ID: NCT02682381

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-23
• Study Completion Date: 2017-08-18

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

0.025 mg/kg/day Teduglutide

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

Group Type: EXPERIMENTAL

Teduglutide 0.025 mg/kg

Intervention Type: DRUG

0.025 mg/kg

0.05 mg/kg/day Teduglutide

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

Group Type: EXPERIMENTAL

Teduglutide 0.05mg/kg

Intervention Type: DRUG

0.05 mg/kg

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.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

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

Interventions

Teduglutide 0.05mg/kg

0.05 mg/kg

Intervention Type: DRUG

Teduglutide 0.025 mg/kg

0.025 mg/kg

Intervention Type: DRUG

Standard of Care

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

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Children's Hospital Los Angeles - RHU

Los Angeles, California, United States

UCLA Dept. of Medicine

Los Angeles, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Georgetown Children's Research Network

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

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Boston Children's Hospital

Boston, Massachusetts, United States

The Nebraska Medical Center

Omaha, Nebraska, United States

Children's Hospital GI Nutrition

New York, New York, United States

Montefiore Medical Center Child Spc

The Bronx, New York, United States

Duke Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Pediatric Specialists

Cleveland, Ohio, United States

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Children's Medical Center Dallas

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Walter C. Mackenzie Health Science Center

Edmonton, Alberta, Canada

British Columbia Children's & Women's Hospital Center

Vancouver, British Columbia, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Helsingin yliopistollinen keskussairaala

Helsinki, , Finland

Universitaetsklinikum Tuebingen

Tübingen, Baden Wuertternberg, Germany

Ospedale Pediatrico Bambino Gesu

Roma, , Italy

Great Ormond Street Hospital for Children

London, Greater London, United Kingdom

Birmingham Children's Hospital

Birmingham, , United Kingdom

Countries

United States; Belgium; Canada; Finland; Germany; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37889619 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol

View Document

Document Type: Study Protocol: Amendment1

View Document

Document Type: Study Protocol: Amendment3

View Document

Document Type: Study Protocol: Amendment4

View Document

Document Type: Study Protocol: Amendment2

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TED-C14-006

Identifier Type: -

Identifier Source: org_study_id