Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome

A Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of teduglutide compared with placebo in subjects with parenteral nutrition (PN)-dependent short bowel syndrome (SBS).

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Teduglutide 0.05 mg/kg/d; Drug: Teduglutide 0.1 mg/kg/d

Detailed Description

Teduglutide is an analog of glucagon-like peptide 2 (GLP-2), a naturally occurring hormone that regulates the growth, proliferation, and maintenance of cells lining the gastrointestinal tract. Teduglutide has been shown in animal studies and previous human clinical trials to increase the size and number of these cells, thereby increasing the absorptive surface area of the intestines.

The multicenter, double-blind, international Phase III trial will randomly assign approximately 80 patients to receive daily subcutaneous injections of 0.05 milligrams or 0.10 milligrams of teduglutide per kilogram of body weight, or a placebo. Dosing will continue for a period of six months. The primary endpoint in the study is a reduction in the use of intravenous feeding, which is often required to sustain life in patients with SBS.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • l'Hôpital Erasme
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H4B9
      • Royal Alexandra Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • St. Paul's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5B1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G2N2
      • Toronto General Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, University of Copenhagen
• France
  • Lille, France, 59037
    • Hôpital Claude-Huriez
  • Lyon, France, 69437
    • Hôpital Edouard Herriot
  • Lyon, France, 69317
    • Hopital de la Croix-Rousse
  • Paris, France, 92110
    • Hopital Beaujon
• Germany
  • Berlin, Germany, 10117
    • Charité University Hospital
  • Berlin, Germany, 13353
    • Charite-Universitatsmedizin Berlin
  • Frankfurt, Germany, 60590
    • Universitatsklinikum Frankfurt
• Netherlands
  • Amsterdam, Netherlands, 1100 DD
    • Academic Medical Center
• Poland
  • Olsztyn, Poland, 10-651
    • Pracownia Żywienia Klinicznego
  • Warsaw, Poland, 00-416
    • Samodzielny Publiczny Szpital Kliniczny-Im.prof W.Orłowskiego CMKP
• United Kingdom
  • Harrow, United Kingdom, HA13UJ
    • St. Mark's Hospital
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M68HD
      • Hope Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Center for Clinical Research
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Penn Nursing
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, aged 18 years of age or older at the time of signing the informed consent form (ICF)
• SBS as a result of major intestinal resection resulting in at least 12 months intravenous feeding
• Body weight must be less than 90 kg
• At baseline, subjects must require PN treatment to meet their caloric or electrolyte needs due to ongoing malabsorption at least 3 times weekly and to be on a stable PN regimen for 4 weeks before dosing
• Body mass index (BMI) 18 to 27 kg/m2
• Adequate hepatic and renal function

Exclusion Criteria:

• History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state
• History of alcohol or drug abuse (within previous year)
• Participation in a clinical study within 30 days prior to signing the ICF, or concurrent participation in any clinical study
• Clinically significant laboratory abnormalities at the time of randomization
• Previous use of teduglutide (ALX-0600)
• Prior use of native GLP-2 within 3 months of screening visit
• Hospital admission within 1 month prior to screening visit
• Pregnant or lactating women
• Any condition or circumstance, which in the investigator's opinion would put the subject at any undue risk, prevent completion of the study, or interfere with analysis of the study results.
• Presence of excluded disease: Radiation enteritis, Scleroderma, Celiac disease, Refractory/Tropical sprue, Pseudo-obstruction, Active inflammatory bowel disease (IBD), Pre-malignant/malignant change in colonoscopy biopsy or polypectomy, Surgery scheduled within the time frame of the study, Human immunodeficiency virus (HIV) positive test, Immunological disorders, Possible allergies to teduglutide or its constituents, Significant, active, uncontrolled, untreated systemic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo injectable subcutaneously daily into the thigh or abdomen	Drug: Placebo; placebo injectable subcutaneously daily into thigh or abdomen
Experimental: 2; teduglutide 0.05 mg/kg/d	Drug: Teduglutide 0.05 mg/kg/d; Teduglutide 0.05 mg/kg/d daily injectable subcutaneously into the thigh or abdomen; Other Names: GATTEX
Experimental: 3; teduglutide 0.1 mg/kg/d	Drug: Teduglutide 0.1 mg/kg/d; Teduglutide 0.1 /g/kg/d daily injection subcutaneously into thigh or abdomen; Other Names: GATTEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A Graded Response Score in Parenteral Nutrition (PN) Reduction	The intensity of the response relied on a reduction from Baseline in weekly parenteral nutrition (PN) volume (minimum reduction of 20% and a maximum of 100%). Duration of the response incorporated responses at Weeks(Wk) 16-20 and at Wk20-24. Zero (0 - lowest) assigned if <20% reduction at Wk20-24 and reduction at Wk16-20 of < 20%, 20-39%, or >=40%. One (1) assigned if reduction of 20-39% at Wk20-24 but < 20% at Wk16-20. Two(2) assigned if reductions of 40-99% at Wk20-24 AND <20% at Wk16-20 OR 20-39% at Wk20-24 AND 20-39% at Wk16-20. Three (3) assigned if reductions of 100% at Wk20-24 AND <20% at Wk16-20 OR 40-99% at Wk20-24 AND 20-39% at Wk16-20 OR 20-39% at Wk20-24 AND >=40% at Wk16-20. Four (4) assigned if reductions of 100% at Wk20-24 AND 20-39% at Wk16-20 OR 40-99% at Wk20-24 AND >=40% at Wk16-20.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24	An efficacy responder was defined as achieving at least a 20% reduction from Baseline to Week 20 and maintained at Week 24 in weekly actual PN infusion volume.	6 months of treatment

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011 Jul;60(7):902-14. doi: 10.1136/gut.2010.218271. Epub 2011 Feb 11.
• Fujioka K, Jeejeebhoy K, Pape UF, Li B, Youssef NN, Schneider SM. Patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal Complaints Independent of Teduglutide. JPEN J Parenter Enteral Nutr. 2017 Nov;41(8):1419-1422. doi: 10.1177/0148607116663481. Epub 2016 Aug 9.
• Dudrick SJ, Latifi R, Fosnocht DE. Management of the short-bowel syndrome. Surg Clin North Am. 1991 Jun;71(3):625-43. doi: 10.1016/s0039-6109(16)45438-1.
• Rombeau JL, Rolandelli RH. Enteral and parenteral nutrition in patients with enteric fistulas and short bowel syndrome. Surg Clin North Am. 1987 Jun;67(3):551-71. doi: 10.1016/s0039-6109(16)44232-5.
• Shanbhogue LK, Molenaar JC. Short bowel syndrome: metabolic and surgical management. Br J Surg. 1994 Apr;81(4):486-99. doi: 10.1002/bjs.1800810404.
• Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology. 1997 Nov;113(5):1767-78. doi: 10.1053/gast.1997.v113.pm9352883.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2004
• Primary Completion (Actual): July 6, 2007
• Study Completion (Actual): July 6, 2007

Study Registration Dates

• First Submitted: April 13, 2004
• First Submitted That Met QC Criteria: April 13, 2004
• First Posted (Estimate): April 14, 2004

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Parenteral Nutrition; Short Bowel Syndrome; SBS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Radiation-Protective Agents; Teduglutide
• Other Study ID Numbers: CL0600-004; 2004-000438-35 (EudraCT Number)