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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00798967
• Collaborator: Nycomed (Industry)
• Enrollment: 86
• Locations: 35
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Short Bowel Syndrome	Drug: teduglutide; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 24-Week Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome
• Actual Study Start Date: Nov 25, 2008
• Actual Primary Completion Date: Jan 25, 2011
• Actual Study Completion Date: Jan 25, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Responder [Weeks 20 and 24]

   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.

Secondary Outcome Measures

1. Absolute Change in PN/I.V. Volume From Baseline to Last Time Point [Week 0 to last visit when data was collected.]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Shire
• Nycomed

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00798967
• Other Study ID Numbers: CL0600-020; 2008-006193-15
• First Posted: Nov 27, 2008
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: SBS; short bowel syndrome; TPN; parenteral nutrition; PN
• Additional relevant MeSH terms: Short Bowel Syndrome; Syndrome; Teduglutide

Study Results

Participant Flow

Recruitment Details	First Patient Screened - November 25, 2008; Last Patient Screened - July 13, 2010; First Patient Randomized - March 3, 2009; Last Patient Randomized - July 22, 2010; Locations - hospitals and transplant centers; Subjects must be on parenteral nutrition (PN) and/or intravenous (I.V.) fluids.
Pre-assignment Detail	Stage 1 was screening, optimization, and stabilization periods. At screening, if the PN/I.V. volume is not stable per protocol, s/he entered an optimization period (up to 8 weeks) to find the minimally tolerated stable volume of PN/I.V.. Prior to randomization, all entered 4-8 weeks of stabilization period on that volume of PN/I.V.

Arm/Group Title	Teduglutide	Placebo
Arm/Group Description	0.05 mg/kg/day subcutaneous (sc) dose of teduglutide	Matching sc dose of placebo to teduglutide
Period Title: Overall Study
STARTED	43	43
Discontinued During Dosing Period	4	4
COMPLETED	39	39
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Teduglutide	Placebo	Total
Arm/Group Description	0.05 mg/kg/day subcutaneous (sc) dose of teduglutide	Matching sc dose of placebo to teduglutide	Total of all reporting groups
Overall Participants	43	43	86
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (12.6)	49.7 (15.6)	50.3 (14.1)
Sex: Female, Male (Count of Participants)
Female	22 51.2%	24 55.8%	46 53.5%
Male	21 48.8%	19 44.2%	40 46.5%

Outcome Measures

1. Primary Outcome

Title	Responder
Description	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.
Time Frame	Weeks 20 and 24

Outcome Measure Data

Analysis Population Description

Percentages were based on the number of subjects in the Intent to Treat (ITT) population.

Arm/Group Title	Teduglutide	Placebo
Arm/Group Description	0.05 mg/kg/day subcutaneous (sc) dose of teduglutide	Matching sc dose of placebo to teduglutide
Measure Participants	43	43
Number [subjects]	27	13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teduglutide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Cochran-Mantel-Haenszel (CMH) test adjusted for the randomization stratification variable (<= 6 or > 6 L/week of PN at baseline)
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Absolute Change in PN/I.V. Volume From Baseline to Last Time Point
Description	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).
Time Frame	Week 0 to last visit when data was collected.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) was defined for efficacy analyses which included all randomized patients.

Arm/Group Title	Teduglutide	Placebo
Arm/Group Description	0.05 mg/kg/day sc dose of teduglutide	Matching sc dose of placebo to teduglutide
Measure Participants	40	43
Mean (Standard Deviation) [Liters/Week]	-4.28 (3.81)	-2.38 (2.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teduglutide, Placebo
	Comments	Last Dosing Visit
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Adverse event data were collected for each subject from the time informed consent was signed to end of study. For this reporting of adverse event, the most commonly reported treatment emergent adverse events (>=3 subjects at SOC level) are listed.
Adverse Event Reporting Description	All adverse experience reporting used the Safety population which consisted of 85 subjects who received at least one dose of study drug. There were 42 subjects treated with teduglutide, whereas 43 subjects received placebo. Adverse experience monitoring was performed through investigator assessment and safety laboratory testing at every visit.
Arm/Group Title	Teduglutide		Placebo
Arm/Group Description	0.05 mg/kg/day subcutaneous (sc) dose of teduglutide		Matching sc dose of placebo to teduglutide
All Cause Mortality
	Teduglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Teduglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/42 (35.7%)		12/43 (27.9%)
Gastrointestinal disorders
Small intestinal stenosis	1/42 (2.4%)	1	0/43 (0%)	0
General disorders
Catheter-related complication	1/42 (2.4%)	1	0/43 (0%)	0
Implant site extravasation	1/42 (2.4%)	1	1/43 (2.3%)	1
Hepatobiliary disorders
Cholecystitis acute	1/42 (2.4%)	1	0/43 (0%)	0
Hepatitis cholestatic	0/42 (0%)	0	1/43 (2.3%)	1
Infections and infestations
Adenovirus infection	1/42 (2.4%)	1	0/43 (0%)	0
Bacteremia	0/42 (0%)	0	3/43 (7%)	3
Catheter sepsis	1/42 (2.4%)	1	0/43 (0%)	0
Catheter-related infection	5/42 (11.9%)	5	1/43 (2.3%)	1
Central line infection	2/42 (4.8%)	2	3/43 (7%)	3
Infective thrombosis	1/42 (2.4%)	1	0/43 (0%)	0
Influenza	1/42 (2.4%)	1	0/43 (0%)	0
Pneumonia	1/42 (2.4%)	1	0/43 (0%)	0
Pneumonia influenzal	0/42 (0%)	0	1/43 (2.3%)	1
Rectal abscess	1/42 (2.4%)	1	0/43 (0%)	0
Soft tissue infection	0/42 (0%)	0	1/43 (2.3%)	1
Urinary tract infection	2/42 (4.8%)	2	1/43 (2.3%)	1
Viral infection	1/42 (2.4%)	1	0/43 (0%)	0
Injury, poisoning and procedural complications
Device breakage	0/42 (0%)	0	1/43 (2.3%)	1
Device dislocation	0/42 (0%)	0	2/43 (4.7%)	2
Device failure	0/42 (0%)	0	1/43 (2.3%)	1
Device malfunction	0/42 (0%)	0	1/43 (2.3%)	1
Fall	0/42 (0%)	0	1/43 (2.3%)	1
Metabolism and nutrition disorders
Dehydration	1/42 (2.4%)	1	0/43 (0%)	0
Psychiatric disorders
Suicide attempt	0/42 (0%)	0	1/43 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/42 (0%)	0	1/43 (2.3%)	1
Vascular disorders
Subclavian vein thrombosis	1/42 (2.4%)	1	0/43 (0%)	0
Other (Not Including Serious) Adverse Events
	Teduglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/42 (83.3%)		34/43 (79.1%)
Gastrointestinal disorders
Abdominal distension	9/42 (21.4%)	14	1/43 (2.3%)	2
Abdominal pain	13/42 (31%)	14	10/43 (23.3%)	14
Diarrhea	3/42 (7.1%)	4	5/43 (11.6%)	7
Flatulence	5/42 (11.9%)	5	3/43 (7%)	3
Nausea	12/42 (28.6%)	19	8/43 (18.6%)	12
Vomiting	5/42 (11.9%)	5	4/43 (9.3%)	10
General disorders
Edema peripheral	7/42 (16.7%)	8	2/43 (4.7%)	3
Fatigue	4/42 (9.5%)	5	3/43 (7%)	3
Pyrexia	4/42 (9.5%)	5	4/43 (9.3%)	5
Infections and infestations
Central line systemic infections	7/42 (16.7%)	12	7/43 (16.3%)	8
Nasopharyngitis	3/42 (7.1%)	3	0/43 (0%)	0
Urinary tract infection	6/42 (14.3%)	6	4/43 (9.3%)	5
Injury, poisoning and procedural complications
Gastrointestinal stoma complication	10/42 (23.8%)	11	3/43 (7%)	3
Investigations
Weight increased	3/42 (7.1%)	3	3/43 (7%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/42 (7.1%)	3	0/43 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of NPS Pharmaceuticals agreements with its investigators may vary. However, NPS does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.