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

NCT02980666 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: SHP633-3022020-005791-35
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 5

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).

Conditions

Short Bowel Syndrome

Outcome Measures

Primary Outcomes (44)

• Absolute Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, milliliter per kilogram per day is abbreviated as mL/kg/day.

  Baseline, EOT (up to Week 24)

• Percent Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data

  Percent change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Absolute Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day).

  Baseline, EOT (up to Week 24)

• Percent Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

  Percent change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Absolute Change From Baseline in Plasma Citrulline at End of Treatment (EOT)

  Absolute change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Percent Change From Baseline in Plasma Citrulline at End of Treatment (EOT)

  Percent change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Absolute Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Percent Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data

  Percent change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Absolute Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Percent Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

  Percent change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 24

  Number of participants who achieved at least 20% reduction in PS volume at Week 24 was reported.

  Week 24

• Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at End of Treatment (EOT)

  Number of participants who achieved at least 20% reduction in PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24)

• Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning of Parenteral Support (PS) Volume at End of Treatment (EOT)

  Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24)

• Number of Participants Who Achieved Greater Than or Equal to (>=) 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 28

  Number of participants who achieved \>= 20% reduction in PS volume at Week 28 was reported.

  Week 28

• Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data

  Absolute change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data

  Percent change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data

  Absolute change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data

  Percent change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Absolute Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)

  Absolute change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Percent Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)

  Percent change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data

  Absolute change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data

  Percent change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data

  Absolute change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data

  Percent change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  EOT (up to Week 24), EOS (up to Week 28)

• Absolute Change From Baseline in Number of Hours Per Day of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in number of hours per day of PS Usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data

  Absolute change from baseline in number of days per Week of PS usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.

  Baseline, EOT (up to Week 24)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An Adverse Event (AE) was 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. TEAEs were defined as any AEs whose onset occurred, severity worsened, or intensity increased after receiving the investigational product.

  From start of study drug administration up to EOS (up to Week 28)

• Change From Baseline in Body Weight for Age Z-score at Week 28

  Body weight was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in body weight for age Z-score at Week 28 was reported.

  Baseline, Week 28

• Change From Baseline in Height for Age Z-score at Week 28

  Height was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in height for age Z-score at Week 28 was reported.

  Baseline, Week 28

• Change From Baseline in Head Circumference for Age Z-score at Week 28

  Head circumference was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in head circumference for age Z-score at Week 28 was reported.

  Baseline, Week 28

• Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)

  Vital sign assessments included pulse rate, blood pressure, or body temperature. Number of participants with clinically significant changes in vital signs by the investigator were recorded as TEAEs.

  From start of study drug administration up to EOS (up to Week 28)

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)

  12-lead ECG was performed. Any change in ECG assessments which were deemed to be clinically significant changes were recorded as TEAEs.

  From start of study drug administration up to EOS (up to Week 28)

• Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)

  Clinical laboratory assessments included biochemistry, hematology, coagulation, urinalysis. The number of participants with clinically significant laboratory abnormalities were reported as TEAEs.

  From start of study drug administration up to EOS (up to Week 28)

• Change From Baseline in the Average Urine Output at Week 28

  Average urine output was recorded in measured volume at Week 28 was recorded.

  Baseline, Week 28

• Change From Baseline in the Fecal Output at Week 28

  Change from baseline in the fecal output (Average number of stools per day) at Week 28 was recorded.

  Baseline, Week 28

• Number of Participants With Positive Specific Antibodies to Teduglutide

  Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies.

  From start of study drug administration up to EOS (up to Week 28)

• Number of Participants With Clinically Significant Abnormal Findings in Gastrointestinal (GI) Specific Testing

  GI specific testing included colonoscopy or sigmoidoscopy, abdominal ultrasound, fecal occult blood testing, upper GI series with small bowel follow-through (UGI/SBFT). EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Number of participants with clinically significant abnormal findings in gastrointestinal specific testing were reported.

  Baseline, EOT (up to Week 24)

• Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide in Plasma

  Since only 2 sparse pharmacokinetics (PK) samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  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) of Teduglutide in Plasma

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

• Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

• Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

• Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

• Apparent Clearance (CL/F) of Teduglutide

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  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) of Teduglutide

  Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

  Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

Study Arms (1)

Teduglutide

EXPERIMENTAL

Participants will receive teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks.

Drug: Teduglutide

Interventions

Teduglutide DRUG

0.05 mg/kg/day SC injection once daily for 24 weeks.

Teduglutide

Eligibility Criteria

• Age: 4 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (5)

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Tsukuba University Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Kagoshima University

Kagoshima, Kagoshima-ken, 890-8520, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Showa University

Shinagawa-ku, Tokyo-To, 142-8555, Japan

Location

Related Publications (1)

• Chiba M, Masumoto K, Kaji T, Matsuura T, Morii M, Fagbemi A, Hill S, Pakarinen MP, Protheroe S, Urs A, Chen ST, Sakui S, Udagawa E, Wada M. Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support. J Pediatr Gastroenterol Nutr. 2023 Sep 1;77(3):339-346. doi: 10.1097/MPG.0000000000003867. Epub 2023 Jun 26.

  PMID: 37364133 DERIVED

MeSH Terms

Conditions

Short Bowel Syndrome

Interventions

teduglutide

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 2, 2016
• Study Start: January 13, 2017
• Primary Completion: January 21, 2020
• Study Completion: January 21, 2020
• Last Updated: February 2, 2022
• Results First Posted: February 10, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5)