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

Phase 3

Completed

Conditions: Short Bowel Syndrome

Interventions: Drug: Teduglutide 0.05mg/kg
Drug: Teduglutide 0.025 mg/kg
Other: Standard of Care

Registration Number: NCT02682381

Lead Sponsor: Shire

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

Inclusion Criteria

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

Exclusion Criteria

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
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
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
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
Body weight < 10 kg at the screening and baseline visits
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
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.
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
Unstable, clinically significant active, untreated pancreatic or biliary disease
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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
0.05 mg/kg/day Teduglutide	Teduglutide 0.05mg/kg	0.05 mg/kg/day of teduglutide for 24 weeks.
0.025 mg/kg/day Teduglutide	Teduglutide 0.025 mg/kg	0.025 milligrams per kilogram per day (mg/kg/day) of teduglutide for 24 weeks.
Standard of care	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline through 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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From start of study treatment up to 28 weeks	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.
Change From Baseline in Enteral Nutrition Volume at Week 24	Baseline, 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.
Change From Baseline in Plasma Citrulline Levels at Week 24	Baseline, Week 24	Plasma citrulline level was reported.
Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	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.
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24	Baseline, Week 24	Change in PN/IV volume was reported based on the participant diary and the investigator prescribed data.
Change From Week 24 in Enteral Nutrition Volume at Week 28	Week 24, 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.
Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24	Baseline, Week 24	Change in PN/IV caloric intake was reported based on the participant diary and the investigator prescribed data.
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28	Week 24, Week 28	Change in PN/IV volume was reported.
Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28	Week 24, 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.
Change From Baseline in Body Weight Z-score at Week 28	Baseline, 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.
Change From Baseline in Body Height Z-score at Week 28	Baseline, 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.
Change From Baseline in Enteral Nutrition Caloric Intake at Week 24	Baseline, 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.
Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28	Week 24, Week 28	Change in PN/IV caloric intake was reported.
Change From Week 24 in Plasma Citrulline Levels at Week 28	Week 24, Week 28	Change in plasma citrulline level was reported.
Change From Baseline in Head Circumference Z-score at Week 28	Baseline, 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.
Change From Baseline in Body Mass Index (BMI) Z-score at Week 28	Baseline, 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.
Change From Baseline in Participants' Stool Consistency at Week 28	Baseline, 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.
Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	Baseline, Week 24	The mean duration of the PN/IV infusions in hours, on the days when PN/IV was administered was reported.
Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24	Baseline, Week 24	The number of days per week of PN/IV infusions were reported.

Trial Locations

Locations (27): UCLA Dept. of Medicine
🇺🇸
Los Angeles, California, United States
Helsingin yliopistollinen keskussairaala
🇫🇮
Helsinki, Finland
Children's Hospital Los Angeles - RHU
🇺🇸
Los Angeles, California, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
The Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
British Columbia Children's & Women's Hospital Center
🇨🇦
Vancouver, British Columbia, Canada
Great Ormond Street Hospital for Children
🇬🇧
London, Greater London, United Kingdom
UCSF Benioff Children's Hospital
🇺🇸
San Francisco, California, United States
Georgetown Children's Research Network
🇺🇸
Washington, District of Columbia, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, 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
🇺🇸
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
University of Wisconsin School of Medicine and Public Health
🇺🇸
Madison, Wisconsin, United States
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Belgium
Walter C. Mackenzie Health Science Center
🇨🇦
Edmonton, Alberta, Canada
Universitaetsklinikum Tuebingen
🇩🇪
Tuebingen, Baden Wuertternberg, Germany
Ospedale Pediatrico Bambino Gesu
🇮🇹
Roma, Italy
Birmingham Children's Hospital
🇬🇧
Birmingham, United Kingdom
Texas Children's Hospital
🇺🇸
Houston, Texas, United States
Ann & Robert H Lurie Children's Hospital of Chicago
🇺🇸
Chicago, Illinois, United States