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

NCT ID: NCT03571516

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-31
• Study Completion Date: 2020-09-24

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Teduglutide

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.

Group Type: EXPERIMENTAL

Teduglutide

Intervention Type: 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.

Standard Medical Therapy

Intervention Type: OTHER

Standard medical therapy will be administered for 24 weeks.

Syringe

Intervention Type: DEVICE

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

Needle

Intervention Type: DEVICE

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

Standard of Care (SOC)

Participants will receive standard medical therapy for 24 weeks.

Group Type: OTHER

Standard Medical Therapy

Intervention Type: OTHER

Standard medical therapy will be administered for 24 weeks.

Syringe

Intervention Type: DEVICE

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

Needle

Intervention Type: DEVICE

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

Interventions

Teduglutide

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

Intervention Type: DRUG

Standard Medical Therapy

Standard medical therapy will be administered for 24 weeks.

Intervention Type: OTHER

Syringe

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

Intervention Type: DEVICE

Needle

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Previous treatment with teduglutide.
• Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc.
• 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:

1. International normalized ratio (INR) greater than (>) 1.5 not corrected with PN vitamin K

2. Platelet count <100×10^3/ microliter (mcL) due to portal hypertension

3. Presence of clinically significant gastric or esophageal varices

4. 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.
• More than 3 serious complications of intestinal failure (example [e.g.], catheter-associated bloodstream infections, interruption of nutrition due to feeding intolerance, catheter-associated thrombosis, severe fluid or electrolyte disturbances) within 1 month prior to or during screening.
• A history of cancer or a known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of gastrointestinal cancer (including hepatobiliary and pancreatic cancers).
• Concurrent treatment with glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); insulin-like growth factor-1 (IGF-1); growth hormone, somatostatin, or analogs of these hormones; or glutamine.
• Participation in a clinical study using an experimental drug within 3 months or 5.5 half-lives of the experimental drug, whichever is longer.
• Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
• 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.

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Shire

Locations

Helsingin yliopistollinen keskussairaala

Helsinki, , Finland

Groupe Hospitalier Pellegrin - Hôpital des Enfants

Bordeaux, Gironde, France

Hopital Jeanne de Flandre - CHRU Lille

Lille, Nord, France

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Great Ormond Street Hospital for Children

London, Greater London, United Kingdom

Royal Manchester Children's Hospital

Manchester, Greater Manchester, United Kingdom

Alder Hey Childrens Hospital

Liverpool, Merseyside, United Kingdom

Birmingham Children's Hospital

Birmingham, West Midlands, United Kingdom

Countries

Finland; France; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37364133 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b5fd94db2bf003ab4709b

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

Other Identifiers

2017-003606-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SHP633-301

Identifier Type: -

Identifier Source: org_study_id