Clinical trial NCT02682381: Short Bowel Syndrome Research Study for Children Up To 17 Years of Age on Parenteral Nutrition
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: Teduglutide
pediatric
GLP-2
parenteral support
Short Bowel Syndrome
short gut syndrome
short gut
SBS
parenteral nutrition
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-02-15
Enrollment: 59
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: Baseline through Week 24
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study treatment up to 28 weeks
measure: Number of Participants Who Were Completely Weaned Off Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
timeFrame: Week 24
measure: Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Plasma Citrulline Levels at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Enteral Nutrition Volume at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Enteral Nutrition Caloric Intake at Week 24
timeFrame: Baseline, Week 24
measure: Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Volume at Week 28
timeFrame: Week 24, Week 28
measure: Change From Week 24 in Parenteral Nutrition Intravenous (PN/IV) Caloric Intake at Week 28
timeFrame: Week 24, Week 28
measure: Change From Week 24 in Plasma Citrulline Levels at Week 28
timeFrame: Week 24, Week 28
measure: Change From Week 24 in Enteral Nutrition Volume at Week 28
timeFrame: Week 24, Week 28
measure: Change From Week 24 in Enteral Nutrition Caloric Intake at Week 28
timeFrame: Week 24, Week 28
measure: Change From Baseline in Body Weight Z-score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Body Height Z-score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Head Circumference Z-score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Body Mass Index (BMI) Z-score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Participants' Stool Consistency at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Hours Per Day of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Days Per Week of Parenteral Nutrition Intravenous (PN/IV) Support at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - RHU
state: California
city: Los Angeles
country: United States
facility: UCLA Dept. of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Washington
country: United States
facility: Georgetown Children's Research Network
state: District of Columbia
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center Child Spc
state: New York
city: New York
country: United States
facility: Children's Hospital GI Nutrition
state: New York
city: Durham
country: United States
facility: Duke Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Pediatric Specialists
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edmonton
country: Canada
facility: Walter C. Mackenzie Health Science Center
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's & Women's Hospital Center
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden Wuertternberg
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: Greater London
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: