Short Bowel Syndrome (SBS) refers to the clinical situation whereby a significant reduction in the absorptive capacity of the intestine results from inadequate anatomical or functional length of residual small intestine following surgical resection. These patients are highly prone to malnutrition, diarrhea, and dehydration due to the reduced intestinal capacity to absorb macronutrients, water and electrolytes (1-8).
Conditions
Interventions
Product Name: Teduglutide
Product Code: ALX - 0600
Pharmaceutical Form: Powder and solvent for solution for injection
Current Sponsor code: ALX - 0600
Other descriptive name: Recombinant glycine2-huma
Sponsors
NPS Allelix Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria can be enrolled in this study: 1.Signed and dated informed consent form (ICF) before any study-related procedures are performed 2.Men and women, aged 18 years of age or older at the time of signing the ICF 3.SBS as a result of major in testinal resection, e.g., due to injury, volvulus, vascular disease, cancer, Crohn’s disease a.For subjects with a history of cancer (there are exceptions listed in Sec. 4.3 Exclusion criteria), the subject should be disease-free for at least 5 years b.For subjects with a history of Crohn’s disease, the subject should be in clinical remission, as determined by clinical assessment 4.Body weight must be less than 90 kg at the time of enrollment 5.Major intestinal resection resulting in at least 12 months dependency prior PN to the date of the signature of ICF. Minor ostomy revisions within this time period are allowable 6.At baseline, subjects must require PN treatment to meet their caloric or electrolyte needs due to ongoing malabsorption at least 3 times weekly 7.Stable for at least 4 consecutive weeks just prior to randomization in: a. Usage and volume of PN b. 48-hour urinary output (1.0 to 2.0 L/d) c. Urine sodium (greater than 20 mmol/d) d. Adequate renal function (serum creatinine and blood urea nitrogen [BUN]1.5 x ULN or less) e. Hct indicating satisfactory hydration (ULN or less) f. Motility altering medications (as defined in the Section 5.4) 8.Body mass index (BMI) 18 to 27 kg/m2 9.Adequate hepatic function: (Alanine aminotransferase [ALT] and aspartate aminotransferase [AST] both less than 2. 0 x ULN; total bilirubin less than 1.25 x ULN; and alkaline phosphatase less than 2.5 x ULN) 10.Female subjects who are not surgically sterile or postmenopausal must use 30 days after medically acceptable methods of birth control during and for the treatment period (see Section 6.2.7). Postmenopausal is defined as aged 60 years or older and 2 years must have elapsed since the last menses. 11.Capable of understanding and be willing to adhere to the study visit schedule and other protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded: 1.History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state. This does not include resected cutaneous basal or squamous cell carcinoma, or in situ cervical cancer. 2.History of alcohol or drug abuse (within previous year) 3.Participation in a clinical study within 30 days prior to signing the ICF, or concurrent participation in any clinical study 4.Clinically significant laboratory abnormalities at the time of randomization 5.Previous use of teduglutide (ALX-0600) 6.Prior use of native GLP-2 within 3 months of screening visit 7.Hospital admission within 1 month prior to screening visit 8.Pregnant or lactating women 9.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 10.Presence of excluded disease. The following is a table of excluded disease states arranged by body systems: Related to SBS Radiation enteritis Scleroderma Celiac disease Refractory or tropical sprue Pseudo-obstruction Gastrointestinal (GI) Active inflammatory bowel disease (IBD) Pre-malignant or malignant change in colonoscopy biopsy or polypectomy Surgery scheduled within the time frame of the study Immune Human immunodeficiency virus (HIV) positive test Immunological disorders Possible allergies to teduglutide or its constituents Cardiovascular, respiratory, renal, endocrine, hepatic, or CNS Significant active, uncontrolled, untreated systemic diseases 11. Failure to adhere to required washout periods. The following table contains lists of certain medications, arranged by the periods of time that must have transpired after stopping them before the first dose of teduglutide in this study. Use of iv insulin is not excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this clinical study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of teduglutide compared with placebo in subjects with PN (Parenteral Nutrition)-dependent SBS. The primary objective is to compare the percentage of subjects treated with teduglutide versus placebo who demonstrate a response at week 20, and who maintain that response through week 24. A response in this study is defined as the achievement of at least a 20% reduction from baseline in weekly PN volume.;Secondary Objective: The secondary efficacy objectives are to evaluate changes in volume of PN, frequency of PN, frequency of iv catheter access, and to evaluate quality of life and utilization of healthcare resources. Additional variables to be evaluated are changes from baseline in parathyroid hormone (PTH), bone markers, bone mineral density (BMD), plasma citrulline, and intestinal mucosal villus height and crypt depth. At selected centers, additional objectives are to evaluate changes in the enteral absorption of gastrointestinal fluid (wet weight), calories, nitrogen, fat, carbohydrate, sodium, magnesium, calcium, and potassium. The safety and tolerability of teduglutide treatments compared with placebo will be assessed. The population PK of teduglutide in subjects with PN-dependent SBS will also be determined.;Primary end point(s): The primary efficacy variable is the percentage of subjects who demonstrate a response at week 20, and who maintain that response through week 24. A response in this study is defined as the achievement of at least a 20% reduction from baseline in weekly PN volume. | — |
Countries
Denmark
Outcome results
None listed