Study in Japanese Pediatric Subjects With Short Bowel Syndrome (SBS) Who Are Dependent on Parenteral Support
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Syndrome
Intervention: Teduglutide
Intervention description: 0.05 mg/kg/day SC injection once daily for 24 weeks.
Intervention MeSH terms: Teduglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 4 Months
Maximum age: 15 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if an investigational treatment (teduglutide) is
      safe and effective in Japanese children (age 4 months through 15 years of age) with SBS who
      are dependent on parenteral support. This study will also evaluate how teduglutide moves
      through the body (pharmacokinetics) and how it affects the body (pharmacodynamics).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent by a parent or guardian prior to any study-related procedures

          -  When applicable, informed assent (as deemed appropriate by the Institutional Review
             Board) by the participant prior to any study-related procedures

          -  Male or female infant 4 to <12 months corrected gestational age or child or adolescent
             aged 1 year through 15 years

          -  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

          -  Stable PN/IV support, defined as:

        For infants 4 to <12 months corrected gestational age: 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 1 month prior to and during screening,
        as assessed by the investigator.

        For children 1 to 15 years of age:

        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.

        Transient instability for events such as interruption of central access or treatment of
        sepsis is allowed if the PN/IV support returns to within 10% of baseline prior to the
        event.

        - Sexually active female participants of childbearing potential must use medically
        acceptable methods of birth control during and for 4 weeks following the last dose of
        investigational product.

        Exclusion Criteria:

          -  Participants 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 other known DNA abnormalities (eg,
             Familial Adenomatous Polyposis, Fanconi-Bickel syndrome)

          -  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 the most recent upper GI series done
             within 6 months prior to screening.

          -  Major GI surgical intervention including significant intestinal resection within 3
             months prior to screening (insertion of feeding tube, anastomotic ulcer repair, minor
             intestinal resections <=10 centimeter (cm), or endoscopic procedure is allowed)

          -  Unstable cardiac disease or congenital heart disease or cyanotic disease, with the
             exception of participants 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 nonaggressive and
             surgically resected cancer. Participants with known cancer predisposition syndrome,
             such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative
             with early onset of GI cancer (including hepatobiliary and pancreatic cancer) will
             also be excluded.

          -  Pregnant or lactating female participants

          -  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 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

          -  Participants 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

          -  Participants 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 serious complications of SBS (eg, documented infection-related catheter
             sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3
             months prior to the screening visit

          -  A serious complication that 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
             participant

          -  Body weight < 5 kilogram (kg) at screening and baseline visits

          -  Signs of active, severe, or unstable clinically significant hepatic impairment during
             the screening period:

        For infants 4 to <12 months corrected gestational age at least 2 of any of the following
        parameters:

          1. International normalized ratio (INR) >1.5 not corrected with parenteral vitamin K

          2. Platelet count <100×10^3/ (microliters)mcL due to portal hypertension

          3. Presence of clinically significant gastric or esophageal varices

          4. Documented cirrhosis

          5. Persistent cholestasis defined as conjugated bilirubin >4 milligram per deciliter
             (mg/dL) (>68 micromoles per liter [mcmol/L]) over a 2 week period

        For children 1 to 15 years of age:

          1. Total bilirubin >= 2x upper limit of normal (ULN)

          2. Aspartate aminotransferase (AST) >= 7x ULN

          3. Alanine aminotransferase (ALT) >= 7x ULN

               -  Signs of known continuous active or unstable, clinically significant renal
                  dysfunction shown by results of an estimated glomerular filtration rate below 50
                  milliliter per minute (mL/min)/1.73 meter (m)^2

               -  Parent(s)/guardian(s) and/or participants 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 participant at any undue risk, prevents completion of the study,
                  or interferes with analysis of the study results.