Safety, Efficacy and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome

NCT03571516 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 2 other identifiers: SHP633-3012017-003606-40
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 8

Brief Summary

The purpose of the study is to evaluate the safety, efficacy/pharmacodynamics (PD) and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral (PN) support.

Conditions

Short Bowel Syndrome

Keywords

Short bowel syndrome; Teduglutide

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)

  Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.

  Baseline, EOT/ET (up to Week 24)

Secondary Outcomes (22)

• Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7)

  Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7

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

  From start of study treatment up to end of study (EOS) (up to Week 28)

• Change From Baseline in Body Weight Z-score at Week 24

  Baseline, Week 24

• Change From Baseline in Length Z-Score at Week 24

  Baseline, Week 24

• Change From Baseline in Head Circumference Z-Score at Week 24

  Baseline, Week 24

Study Arms (2)

Teduglutide

EXPERIMENTAL

Participants will receive 0.05 milligram per kilogram (mg/kg) subcutaneous (SC) injection of teduglutide into abdomen or into either the thigh or arm once daily (QD) in addition to standard medical therapy for 24 weeks.

Drug: Teduglutide; Other: Standard Medical Therapy; Device: Syringe; Device: Needle

Standard of Care (SOC)

OTHER

Participants will receive standard medical therapy for 24 weeks.

Other: Standard Medical Therapy; Device: Syringe; Device: Needle

Interventions

Teduglutide DRUG

SC injection of 0.05 mg/kg teduglutide will be administered QD into abdomen or into either the thigh or arm for 24 weeks.

Teduglutide

Standard Medical Therapy OTHER

Standard medical therapy will be administered for 24 weeks.

Standard of Care (SOC); Teduglutide

Syringe DEVICE

Teduglutide will be administered using syringe (510k number: K980987).

Standard of Care (SOC); Teduglutide

Needle DEVICE

Teduglutide will be administered using needle (510k number: K021475).

Standard of Care (SOC); Teduglutide

Eligibility Criteria

• Age: 4 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed consent by the parent or legal guardian.
• Male or female infant 4 to 12 months corrected gestational age at screening.
• Weight at least 5 kilogram (kg) and weight-for-length Z-score greater than -2 at screening and baseline.
• Short bowel syndrome with dependence on parenteral support to provide at least 50% of fluid or caloric needs.
• Stable PN requirements for at least 1 month prior to screening, defined as a less than or equal to (\<=) 10% change in the weight-normalized PN total fluid and caloric intake, despite attempts to wean PN, not withstanding transient instability for events such as sepsis or interruption of central venous access.
• Parent or legal guardian understands and is willing and able to fully adhere to study requirements as defined in this protocol.

You may not qualify if:

• Previous treatment with teduglutide.
• 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 PN support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding.
• Inability to advance oral or enteral feeding due to lack of access to the gut, such as oral aversion in the absence of a feeding tube.
• Intestinal obstruction or clinically significant intestinal stenosis.
• Major gastrointestinal surgical intervention, such as serial transverse enteroplasty or major intestinal resection or anastomosis, within 3 months prior to screening or planned during the study period.
• Unstable cardiac disease.
• Renal dysfunction, defined as estimated glomerular filtration rate less than (\<) 50 milliliter per minute (mL/min) per 1.73 square meter (m\^2).
• Biliary obstruction, stenosis, or malformation.
• Clinically significant pancreatic disease.
• Severe hepatic dysfunction or portal hypertension, defined by at least 2 of the following parameters:
• International normalized ratio (INR) greater than (\>) 1.5 not corrected with PN vitamin K
• Platelet count \<100×10\^3/ microliter (mcL) due to portal hypertension
• Presence of clinically significant gastric or esophageal varices
• Documented cirrhosis
• Persistent cholestasis defined as conjugated bilirubin \>4 milligram per deciliter (mg/dL) (\>68 micromoles per liter \[mcmol/L\]) over a 2 week period.

Sponsors & Collaborators

• Shire: lead

Study Sites (8)

Helsingin yliopistollinen keskussairaala

Helsinki, 00290, Finland

Location

Groupe Hospitalier Pellegrin - Hôpital des Enfants

Bordeaux, Gironde, 33000, France

Location

Hopital Jeanne de Flandre - CHRU Lille

Lille, Nord, 59037, France

Location

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

Great Ormond Street Hospital for Children

London, Greater London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Alder Hey Childrens Hospital

Liverpool, Merseyside, L12 2AP, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

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

Related Links

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

MeSH Terms

Conditions

Short Bowel Syndrome

Interventions

teduglutide; 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@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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: June 27, 2018
• Study Start: August 31, 2018
• Primary Completion: September 24, 2020
• Study Completion: September 24, 2020
• Last Updated: May 11, 2021
• Results First Posted: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); FI (1); IT (1); GB (4)