Long-term Safety and Efficacy Study of Teduglutide in Pediatric Participants With Short Bowel Syndrome (SBS)

NCT02954458 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 2 other identifiers: SHP633-3042016-000849-30
• Study Type: interventional
• Target: 61
• Locations: 6 countries
• Sites: 22

Brief Summary

This study will follow participants who completed the TED-C14-006 study. The purpose of this study is to evaluate the long-term safety and efficacy of teduglutide in pediatric participants with Short Bowel Syndrome (SBS). This study will also offer teduglutide treatment to eligible participants, regardless of treatment received in TED-C14-006 or SHP633-301.

Conditions

Short Bowel Syndrome

Outcome Measures

Primary Outcomes (20)

• 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 AEs that started or worsened on or after the date of first dose of teduglutide for participants in the TED/TED, TED/NTT, and NTT/TED treatment groups, or after the core study baseline visit for participants in the NTT/NTT group.

  From start of study drug administration up to follow-up (up to 46 months)

• Change From Baseline in Average Total Urine Output at End of Treatment (EOT) of Last Cycle During Teduglutide Treatment

  Average total urine output was recorded over a 48-hour period of parental support (PS) stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily urine output milliliter per kilogram per day (mL/kg/day) was calculated as: Total urine output over 48 hours / 2) / body weight (kilogram \[kg\]) where total urine output was calculated as the sum of the urine output in milliliter (mL) and the urine-only diaper weights in gram (g) (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF).

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Average Total Urine Output at Last Visit During Non-Teduglutide Treatment (NT)

  Average total urine output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. Average daily urine output mL/kg/day was calculated as: (Total urine output over 48 hours/2) / body weight (kg) where total urine output was calculated as the sum of the urine output in mL and the urine-only diaper weights in gram (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF).

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Average Number of Stools Per Day at EOT of Last Cycle During Teduglutide Treatment

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2).

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Average Number of Stools Per Day at Last Visit During Non-Teduglutide Treatment (NT)

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2).

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at EOT of Last Cycle During Teduglutide Treatment

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day \[g/kg/day\]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day).

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at Last Visit During Non-Teduglutide Treatment (NT)

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day \[g/kg/day\]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day).

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Average Total Ostomy Output at EOT of Last Cycle During Teduglutide Treatment

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day (mL/kg/day).

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Average Total Ostomy Output at Last Visit During Non-Teduglutide Treatment (NT)

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day.

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Average Bristol Stool Form Score at EOT of Last Cycle During Teduglutide Treatment

  Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily fecal output was summarized the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). Typical Stool Form based on Bristol Stool Form Scale: 1 - Separate hard lumps, hard to pass, 2 - Sausage-shaped, but lumpy, 3 - Like a sausage but with cracks on the surface, 4- Like a sausage or snake, smooth and soft, 5- Soft blobs with clear-cut edges, 6- Fluffy pieces with ragged edges, a mushy stool, 7- Watery, no solid pieces. Entirely liquid.

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Average Bristol Stool Form Score at Last Visit During Non-Teduglutide Treatment (NT)

  Fecal output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized separately the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). Typical Stool Form based on Bristol Stool Form Scale: 1- Separate hard lumps, hard to pass, 2- Sausage-shaped, but lumpy, 3- Like a sausage but with cracks on the surface, 4 - Like a sausage or snake, smooth and soft, 5- Soft blobs with clear-cut edges, 6- Fluffy pieces with ragged edges, a mushy stool, 7- Watery, no solid pieces. Entirely liquid.

  Baseline, Last visit in NT (up to Month 39)

• Number of Participants With Positive Specific Antibodies at End of Study (EOS)

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

  At EOS (up to 46 months)

• Change From Baseline in Body Weight Z-score at EOT of Last Cycle During Teduglutide Treatment

  Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Body Weight Z-score at Last Visit During Non-Teduglutide Treatment (NT)

  Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Height Z-score at EOT of Last Cycle During Teduglutide Treatment

  Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Height Z-score at Last Visit During Non-Teduglutide Treatment

  Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Head Circumference Z-score at EOT of Last Cycle During Teduglutide Treatment

  Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Head Circumference Z-score at Last Visit During Non-Teduglutide Treatment (NT)

  Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline in Body Mass Index (BMI) Z-score at EOT of Last Cycle During Teduglutide Treatment

  BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Body Mass Index (BMI) Z-score at Last Visit During Non-Teduglutide Treatment (NT)

  BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

  Baseline, Last visit in NT (up to Month 39)

Secondary Outcomes (19)

• Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Diary Parenteral Support (PS) Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Prescribed PS Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Percent Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline in Prescribed PS Volume at EOT of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

Other Outcomes (6)

• Change From Baseline In Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score at EOT of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

• Change From Baseline In PedsQL GCS Score at Last Visit During Non-Teduglutide Treatment (NT)

  Baseline, Last visit in NT (up to Month 39)

• Change From Baseline In PedsQL Total Family Impact Module Score at EOT of Each Cycle During Teduglutide Treatment

  Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)

Study Arms (1)

Standard of care (SOC) treatment +/- teduglutide (TED)

EXPERIMENTAL

Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment.

Drug: TED; Other: SOC; Device: Syringe; Device: Needle

Interventions

TED DRUG

0.05 mg/kg SC injection once daily.

Standard of care (SOC) treatment +/- teduglutide (TED)

SOC OTHER

Standard safety assessments and adjustments in nutritional support.

Standard of care (SOC) treatment +/- teduglutide (TED)

Syringe DEVICE

Teduglutide will be administered using syringe.

Standard of care (SOC) treatment +/- teduglutide (TED)

Needle DEVICE

Teduglutide will be administered using needle.

Standard of care (SOC) treatment +/- teduglutide (TED)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant provides written informed consent (participant, parent or legal guardian and, as appropriate, informed assent) to participate in the study before completing any study-related procedures.
• Participant completed the TED-C14-006 or SHP633-301 studies (including participants in the standard of care treatment arms). Participants are considered to have completed SHP633-301 if they completed study assessments through week 24.
• Participant understands and is willing and able to fully adhere to study requirements as defined in this protocol.

Sponsors & Collaborators

• Shire: lead

Study Sites (22)

Childrens Hospital Los Angeles - RHU

Los Angeles, California, 90027-6062, United States

Location

Mattel Children's Hospital UCLA

Los Angeles, California, 90095, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158-2531, United States

Location

Georgetown Children's Research Network

Washington D.C., District of Columbia, 20007, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

The Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Columbia Unversity Medical Center

New York, New York, 07024, United States

Location

Children's Hosp. at Montefiore

The Bronx, New York, 10467-2403, United States

Location

Duke Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Woluwe-Saint-Lambert, 1200, Belgium

Location

Walter C. Mackenzie Health Science Centre

Edmonton, Alberta, T6G 1C9, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Helsingin yliopistollinen keskussairaala

Helsinki, 00290, Finland

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Great Ormond Children's Hosp

London, Greater London, WC1N 3JH, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Short Bowel Syndrome

Interventions

Syringes; Needles

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Equipment and Supplies

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.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 2, 2016
• First Posted: November 3, 2016
• Study Start: January 9, 2017
• Primary Completion: November 5, 2020
• Study Completion: November 5, 2020
• Last Updated: March 28, 2025
• Results First Posted: October 13, 2021

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); CA (2); BE (1); US (15); FI (1); IT (1)