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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Placebo
* Drug: Teduglutide 0.05 mg/kg/d
* Drug: Teduglutide 0.1 mg/kg/d


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBS, Short Bowel Syndrome, Parenteral Nutrition