Short Bowel Syndrome MedDRA version: 12.0 Level: LLT Classification code 10049416 Term:
Conditions
Interventions
Product Name: teduglutide
Product Code: ALX-0600
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Teduglutide
CAS Number: 197922-42-2
Current Sponsor code: ALX-0600
Concentr
Sponsors
NPS Pharmaceuticals, Inc.
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, 18 years of age or older at the time of signing the ICF 3. Intestinal failure resulting in SBS as a consequence of major intestinal resection (eg, due to injury, volvulus, vascular disease, cancer, Crohn’s disease) 4. For subjects with a history of Crohn’s disease, the subject should be in clinical remission for at least 12 weeks prior to dosing as demonstrated by clinical assessment, which may include procedure-based evidence of remission 5. Subjects who have undergone intestinal resection resulting in at least 12 continuous months of parenteral nutrition (PN) dependency prior to signature of ICF 6. PN required at least 3 times per week during the week before screening and during the 2 weeks prior to baseline to meet their caloric, fluid, or electrolyte needs due to ongoing malabsorption 7. Stable PN for at least 4 consecutive weeks immediately prior to randomization based upon the opinion of the investigator and approval of NPS. Stability is described as: a. Actual PN/IV usage should match prescribed PN/IV b. Baseline (V2) 48-hour oral fluid intake and urine output (I/O) volumes should fall within ±25% of the respective 48-hour I/O volumes at the time subject is optimized and enters stabilization. c. Urine output volume should NOT fall below 2 L and not exceed 4 L per 48 hours when the subject completes the optimization and stabilization periods 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 non-aggressive and surgically resected cancer. 2. Participation in a clinical study using an experimental drug within 30 days or an experimental antibody treatment within 90 days prior to signing the ICF, or concurrent participation in any clinical study using an experimental drug. 3. Previous use of native GLP-2 or human growth hormone (HGH) within 6 months prior to screening. Previous use of IV glutamine, octreotide, GLP-1 analog , or DPP-IV inhibitors within 30 days prior to screening. 5. Previous use of teduglutide 6. Subjects with Crohn’s disease who have been treated with biological therapy (eg, anti-TNF or natalizumab) within the 6 months prior to screening 7. Subjects with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that has been introduced or changed during the last 3 months. 8. More than 4 SBS-related or PN-related hospital admissions (eg, catheter sepsis, bowel obstruction, severe water-electrolytes disturbances) within 12 months prior to screening visit 9. Hospital admission, other than scheduled, within 1 month prior to screening 10. Pregnant or lactating women 11. Body weight > 88 kg 12. Body mass index (BMI) <15 kg/m2 13. Signs of severe hepatic impairment or disturbed renal function: a. Total bilirubin = 2xULN - For subjects with Gilbert’s disease, direct (conjugated) bilirubin = 2xULN. b. Aspartate aminotransferase (AST) = 5xULN c. Serum creatinine = 2xULN Female subjects who are not surgically sterile or postmenopausal (defined as aged 55 years or older and/or at least 2 years have elapsed since her last menses) or who are not using medically acceptable methods of birth control during and for 30 days after the treatment period. 15. Not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements. 16. Any condition or circumstance that 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. 17. Presence of any of the excluded disease states described in Table 4-1 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 is defined as the achievement of at least a 20% reduction from baseline in weekly PN volume. ;Secondary Objective: The secondary objectives are to evaluate efficacy variables based on reductions in parenteral nutrition (PN)/IV volume or the direct effects of improved intestinal absorption of fluid. The variables include: duration of response (ie, total number of weeks at =20% reduction from baseline); the proportion of patients with a =20% reduction or a =2 L reduction from baseline in weekly PN at Week 20 and maintained through Week 24; the number of subjects who stop PN and time of discontinuation; and absolute change and percent change in PN between baseline and last dosing visit. An additional secondary efficacy variable is an ordered categorical (or graded) response that accounts for both intensity and duration of the response at the end of the 24-week treatment period. The intensity of the response relies on a reduction from baseline in weekly PN volume at a minimum of 20% and a maximum of 100%. Duration of the response incorporates responses at weeks 16 through 20 and at weeks 20 through 24.;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 is defined as the achievement of at least a 20% reduction from baseline in weekly PN volume. The weekly actual PN/IV volume will be used in the analyses. | — |
Countries
Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed