Short Bowel Syndrome Research Study for Children Up To 17 Years of Age on Parenteral Nutrition
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Syndrome
Intervention: Teduglutide 0.05mg/kg; Teduglutide 0.025 mg/kg; Standard of Care
Intervention description: 0.05 mg/kg; 0.025 mg/kg; Observational cohort for the 24-week treatment period and 4 week follow-up.
Intervention MeSH terms: Teduglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 59.0
Sex: All
Minimum age: 0 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Teduglutide; pediatric; GLP-2; parenteral support; Short Bowel Syndrome; short gut syndrome; short gut; SBS; parenteral nutrition

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.