Study of Teduglutide Effectiveness in Parenteral Nutrition (PN)-Dependent Short Bowel Syndrome (SBS) Subjects (STEPS)

A 24-Week Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome

Teduglutide is an investigative medicine being evaluated as a possible treatment for people with parenteral nutrition (PN) dependent Short Bowel Syndrome (SBS). Teduglutide is similar to a protein the body makes. When people have SBS, their bodies do not make enough of the protein and they have trouble getting nutrients and fluids from the food they eat and drink. This study was designed to provide evidence of efficacy, safety, and tolerability of teduglutide 0.05 mg/kg daily in SBS subjects.

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: teduglutide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • Critical Care Research, Royal Alexandra Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences Centre
    • North York, Ontario, Canada, M3H 5S4
      • Polyclinic Family and Specialty Medicine Facility
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network - Toronto General Hospital
• Denmark
  • København, Denmark, 2100
    • Rigshospitalet - Abdominalcentret, Hepatologisk Kilinik A
• France
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Lyon, France
    • Hôpital Croix Rousse Unité de Nutrition Clinique Intensive
  • Nice Cedex 3, France, 06100
    • Hôpital de l'Archet Pôle Digestif
• Germany
  • BE
    • Berlin, BE, Germany, 13353
      • Med. Klinik m.S. Hepatologie und Gastroenterologie
  • BW
    • Tuebingen, BW, Germany, 72076
      • Universitaetsklinikum Tuebingen
  • HH
    • Hamburg, HH, Germany, 22297
      • Israelitisches Krankenhaus
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sant'Orsola - Malpighi centro insufficienza intestinale
  • Napoli, Italy, 80131
    • Azienda Universitaria Policlinico Federico II
  • TO
    • Torino, TO, Italy, 10126
      • Azienda Ospedaliera Universitaria S. Giovanni Battista - Le Molinette
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Universitair Medisch Centrum St. Radboud
• Poland
  • Lodz, Poland, 90-531
    • Wojewodzki Szpital Specjalistyczny im. M. Pirogowa, Pracownia Leczenia Zywieniowego
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Chirurgii Ogolnej i Transplantacyjnej
  • Olsztyn, Poland, 10-561
    • Wojewodzki Szpital Specjalistyczny,
  • Warsaw, Poland, 00-416
    • Samodzielny Publiczny Szpital Kliniczny im. prof W. Orlowskiego CMKP, Oddzial Kliniczny Zywienia i Chirurgii
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• United Kingdom
  • Gt Lon
    • Harrow, Gt Lon, United Kingdom, HA1 3UJ
      • St. Mark's Hospital Northwick Park
    • London, Gt Lon, United Kingdom, NW1 2BU
      • University College Hospital
  • Gt Man
    • Manchester, Gt Man, United Kingdom, M6 8HD
      • Green Area, Main Hospital Salford Royal Hospitals NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic & Research Foundation
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennslyvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

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:

• Signed and dated informed consent prior to any study-related procedures are performed
• Men and women 18 years of age or older at the time of informed consent signing
• Intestinal failure resulting in Short Bowel Syndrome
• At least 12 months of continuous PN dependency
• 12 weeks of clinical remission of Crohn's disease (CD) prior to dosing
• PN required at least 3 times weekly
• A stable PN volume for four weeks prior to dosing

Exclusion Criteria:

• History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state
• Participation in clinical study within 30 days for drug or 90 days for antibody
• Use of native GLP-2 or human growth hormone (HGH) within 6 months of screening
• Use of iv glutamine within 30 days prior to screening
• Use of teduglutide
• CD patients who have been treated with biological therapy within 6 months of screening
• IBD patients who require chronic systemic immunosuppressant therapy
• More than 4 SBS- or PN-related hospitalizations within 12 months of screening
• Unplanned hospitalization within one month of screening
• Pregnant or lactating women
• Body weight > 88kg
• Body mass index (BMI) < 15 kg/m2
• Severe hepatic impairment or disturbed renal function
• Female subjects who are not surgically sterile or postmenopausal or who are not using medically acceptable methods of birth control during and for 30 days after the treatment period
• Not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements
• Any condition or circumstance that is the investigator's opinion would put the subject at any undue risk, prevent completion of the study, or interfere with the analysis of the study results
• 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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teduglutide; 0.05 mg/kg/day sc dose of teduglutide	Drug: teduglutide; 0.05 mg/kg/day sc injection for 24 weeks; Other Names: GATTEX; ALX-0600
Placebo Comparator: Placebo; Matching subcutaneous dose of placebo to teduglutide	Drug: placebo; Matching daily subcutaneous dose of placebo to teduglutide for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder	Comparison of subjects treated with teduglutide to placebo who achieve a 20 to 100% reduction from baseline in weekly parenteral nutrition/intravenous fluid (PN/I.V.) volume at weeks 20 and 24.	Weeks 20 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in PN/I.V. Volume From Baseline to Last Time Point	Absolute change in the volume of PN/I.V. from baseline (Week 0) to the visit when the last data point was collected (week 4 through week 24, or earlier if the subject discontinued early).	Week 0 to last visit when data was collected.

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: Nycomed

Publications and helpful links

General Publications

• Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR, Gregory J, Tappenden KA, Holst J, Mortensen PB. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut. 2005 Sep;54(9):1224-31. doi: 10.1136/gut.2004.061440.
• Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Citrulline correlations in short bowel syndrome-intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study. Clin Nutr. 2020 Aug;39(8):2479-2486. doi: 10.1016/j.clnu.2019.11.001. Epub 2019 Nov 9.
• Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure. Gastroenterology. 2018 Mar;154(4):874-885. doi: 10.1053/j.gastro.2017.11.023. Epub 2017 Nov 22.
• 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.
• Vipperla K, O'Keefe SJ. Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel syndrome subjects. Expert Rev Gastroenterol Hepatol. 2013 Nov;7(8):683-7. doi: 10.1586/17474124.2013.842894. Epub 2013 Oct 17.
• Jeppesen PB, Pertkiewicz M, Forbes A, Pironi L, Gabe SM, Joly F, Messing B, Loth S, Youssef NN, Heinze H, Berghofer P. Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study. Clin Nutr. 2013 Oct;32(5):713-21. doi: 10.1016/j.clnu.2013.03.016. Epub 2013 Mar 28.
• Berghofer P, Fragkos KC, Baxter JP, Forbes A, Joly F, Heinze H, Loth S, Pertkiewicz M, Messing B, Jeppesen PB. Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL) scale. Clin Nutr. 2013 Oct;32(5):789-96. doi: 10.1016/j.clnu.2012.12.001. Epub 2012 Dec 12.
• Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O'keefe SJ, Forbes A, Heinze H, Joelsson B. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012 Dec;143(6):1473-1481.e3. doi: 10.1053/j.gastro.2012.09.007. Epub 2012 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2008
• Primary Completion (Actual): January 25, 2011
• Study Completion (Actual): January 25, 2011

Study Registration Dates

• First Submitted: November 25, 2008
• First Submitted That Met QC Criteria: November 26, 2008
• First Posted (Estimate): November 27, 2008

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: short bowel syndrome; parenteral nutrition; PN; SBS; TPN
• 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: CL0600-020; 2008-006193-15 (EudraCT Number)