Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study in Japanese Pediatric Subjects With Short Bowel Syndrome (SBS) Who Are Dependent on Parenteral Support

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02980666
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Brief 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).

Condition or disease Intervention/treatment Phase
Short Bowel Syndrome Drug: Teduglutide Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 24-week Safety, Efficacy, Pharmacodynamic, and Pharmacokinetic Study of Teduglutide in Japanese Pediatric Subjects, Aged 4 Months Through 15 Years, With Short Bowel Syndrome Who Are Dependent on Parenteral Support
Actual Study Start Date : January 13, 2017
Estimated Primary Completion Date : April 12, 2019
Estimated Study Completion Date : April 12, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Teduglutide

Arm Intervention/treatment
Experimental: Teduglutide
Participants will receive teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks.
Drug: Teduglutide
0.05 mg/kg/day SC injection once daily for 24 weeks.




Primary Outcome Measures :
  1. Change From Baseline in Parenteral Nutrition/Intravenous Fluids (PN/IV) Support [ Time Frame: Baseline up to Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results.

  2. Change from Baseline in Plasma Citrulline Levels [ Time Frame: Baseline up to Week 24 ]
    Plasma citrulline levels will be measured as a biomarker of enterocyte mass.

  3. Change from Baseline in Enteral Nutritional (EN) Support [ Time Frame: Baseline up to Week 24 ]
    Advances in enteral nutrition support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results.

  4. Number of Participants Achieving At least 20 percent (%) Parenteral Nutrition/Intravenous Fluids Reduction [ Time Frame: Baseline, Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Participants with reduction in PN/IV volume of at least 20% at the end of treatment will be considered for this analysis.

  5. Number of Participants Achieving 100% Reduction in Parenteral Nutrition/Intravenous Fluids Volume [ Time Frame: Baseline, Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Participants achieving 100% reduction in PN/IV volume (complete weaning of PN/IV support) will be determined according to the weaning algorithms.

  6. Number of Participants Achieving Greater Than or Equal to (>=) 20% Reduction in Parenteral Nutrition/Intravenous Fluids Volume [ Time Frame: Baseline up to Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Participants with >= 20% reduction in PN/IV volume at each visit will be considered for this analysis.

  7. Change From Week 24 to Week 28 in Parenteral Nutrition/Intravenous Fluids Support [ Time Frame: Week 24, Week 28 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Change from week 24 to week 28 will be considered for this analysis.

  8. Change From Week 24 to Week 28 in Plasma Citrulline Levels [ Time Frame: Week 24, Week 28 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Change from week 24 to week 28 in plasma citrulline levels will be measured as a biomarker of enterocyte mass.

  9. Change From Week 24 to Week 28 in Enteral Nutrition Support [ Time Frame: Week 24, Week 28 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Change from week 24 to week 28 in in EN support will be considered for analysis.

  10. Change in Hours per Day of Parenteral Nutrition/Intravenous Fluids Support [ Time Frame: Baseline up to Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Change in hours per day of PN/IV support will be measured.

  11. Change in Days per Week of Parenteral Nutrition/Intravenous Fluids Support [ Time Frame: Baseline up to Week 24 ]
    PN/IV support will be provided to maintain energy, fluid and electrolyte homeostasis. Advances in reductions to PN/IV support will be based on clinical status, including weight, linear growth, hydration status, and safety laboratory results. Change in days per week of PN/IV support will be measured.

  12. Number of Participants With Adverse Events (AEs), Including Those Pertaining to Gastrointestinal (GI) Symptoms [ Time Frame: Baseline to Week 28 ]
    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. GI symptoms during the screening period will be recorded in a GI-specific symptoms history diary on a daily basis.

  13. Number of Participants With Physical Examination Parameters Reported as Adverse Events [ Time Frame: Baseline to Week 28 ]
    Physical examinations will be performed, and body weight, height (or length), and head circumference (up to 36 months of age) will be measured.

  14. Number of Participants With Vital Signs Reported as Adverse Events [ Time Frame: Baseline to Week 28 ]
    Vital signs include body temperature, heart rate and systolic and diastolic blood pressure.

  15. Number of Participants With Electrocardiogram (ECG) Assessments Reported as Adverse Events [ Time Frame: Baseline to Week 28 ]
    Twelve-lead ECGs will be performed.

  16. Number of Participants With Clinical Laboratory Tests Reported as Adverse Events [ Time Frame: Baseline to Week 28 ]
    Clinical laboratory tests include biochemistry, hematology, coagulation, urinalysis, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin.

  17. Change From Baseline in the Urine Output [ Time Frame: Baseline to Week 28 ]
    Urine output will be recorded in measured volume.

  18. Change From Baseline in the Fecal Output [ Time Frame: Baseline to Week 28 ]
    Fecal output will be recorded.

  19. Number of Participants Having Positive Specific Antibodies to Teduglutide [ Time Frame: Baseline, Week 24, Week 28 ]
    Number of participants classified as having positive specific antibodies to teduglutide will be used to summarize the presence of antibodies.

  20. Number of Participants With Abnormal Findings in Gastrointestinal (GI) Specific Testing [ Time Frame: Baseline, Week 12, Week 24 ]
    GI specific testing includes colonoscopy or sigmoidoscopy, abdominal ultrasound, fecal occult blood testing, upper GI series with small bowel follow-through (UGI/SBFT).

  21. Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Area under the concentration-time curve at steady-state (AUCtau,ss) will be assessed.

  22. Maximum Plasma Concentration at Steady-state (Cmax,ss) of Teduglutide in Plasma [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Maximum plasma concentration at steady-state (Cmax,ss) will be assessed.

  23. Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Minimum plasma concentration (Cmin,ss) will be assessed.

  24. Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Time to reach maximum observed drug concentration of Teduglutide during a dosing interval will be assessed.

  25. Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Terminal-phase half-life (t1/2) will be assessed.

  26. Apparent Clearance (CL/F) of Teduglutide [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    CL/F is defined as the volume of plasma cleared of the drug per unit time during a dosing interval.

  27. Apparent Volume of Distribution (V[lambda z]/F) of Teduglutide [ Time Frame: Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose ]
    Apparent volume of distribution (V[lambda z]/F) will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   4 Months to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980666


Contacts
Layout table for location contacts
Contact: Shire Contact 1 866-842-5335 ClinicalTransparency@shire.com

Locations
Layout table for location information
Japan
Kyushu University Hospital Recruiting
Fukuoka-shi, Fukuoka-ken, Japan, 812-8582
Contact: Toshiharu Matsuura    +819264111151    matsuura@pedsurg.med.kyushu-u.ac.jp   
Principal Investigator: Toshiharu Matsuura, MD         
Tsukuba University Hospital Recruiting
Tsukuba, Ibaraki-Ken, Japan, 305-8576
Contact: Kouji Masumoto    +181298533900    kmasu@md.tsukuba.ac.jp   
Principal Investigator: Kouji Masumoto, MD         
Kagoshima University Recruiting
Kagoshima-shi, Kagoshima-Ken, Japan, 890-8520
Contact: Tatsuru Kaji    +81992755111    tatu@m2.kufm.kagoshima-u.ac.jp   
Principal Investigator: Tatsuru Kaji, MD         
Tohoku University Hospital Recruiting
Sendai-shi, Miyagi-Ken, Japan, 980-8574
Contact: Motoshi Wada    +81227177000      
Principal Investigator: Motoshi Wada, MD         
Showa University Recruiting
Shinagawa-ku, Tokyo-To, Japan, 142-8555
Contact: Masahiro Chiba    +81337848000      
Principal Investigator: Masahiro Chiba, MD         
Sponsors and Collaborators
Shire
Investigators
Layout table for investigator information
Study Director: Study Director Shire

Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02980666     History of Changes
Other Study ID Numbers: SHP633-302
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Short Bowel Syndrome
Disease
Pathologic Processes
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Teduglutide
Gastrointestinal Agents
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs