Short Bowel Syndrome
Conditions
Keywords
Short Bowel Syndrome, Intestinal Failure, SBS, SBS-IF, GLP-2, Short Bowel Syndrome Intestinal Failure
Brief summary
The primary objective of the trial is the confirmation of the efficacy of apraglutide to evaluate the efficacy of weekly subcutaneous apraglutide in reducing parenteral support dependency.
Detailed description
This is an international, multicenter, double-blind, randomized, placebo-controlled, trial to evaluate the efficacy and safety of weekly SC injections of apraglutide in adult subjects with SBS-IF. The active pharmaceutical ingredient is apraglutide, a GLP-2 analogue. The trial consists of a screening phase, a treatment phase of 48 weeks, and a safety follow-up phase. Trial participants will receive, after successful screening, once weekly apraglutide.
Interventions
DRUGapraglutide
Apraglutide is a peptide analogue of GLP-2 under development for treatment of SBS-IF, which acts as a full agonist at the GLP-2 receptor with in vitro potency and selectivity comparable with native GLP-2.
Sponsors
VectivBio AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent for this trial prior to any trial specific assessment. 2. Male and female subjects with SBS-IF, receiving parenteral support (PS), secondary to surgical resection of the small intestine with either stoma or colon-in-continuity (CIC). 3. Subject must require PS at least 3 days per work and be considered stable. 4. No restorative surgery intended to change PS requirements in the trial period. 5. Age ≥18 years at screening.
Exclusion criteria
1. Pregnancy or lactation. 2. Major abdominal surgery in the last 6 months prior to screening. 3. History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer. 4. Evidence of active inflammatory GI conditions in the previous 6 months. 5. Evidence of decompensated heart failure. 6. Evidence of severe renal or hepatic impairment. 7. Any previous use of growth factors such as growth hormone (GH), native GLP-2, GLP-1, or GLP-2 or GLP-1 analogues should be discussed with the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative change from baseline in actual weekly PS volume at Week 24. | At week 24 of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis | Weeks 0 / 24 of treatment |
| At least 40% reduction of PS volume at Weeks 20 and 24 (Stoma only) | Weeks 20 / 24 of treatment |
| Trough plasma concentrations (Ctrough) at every other visit during the prolonged dosing period (CIC only) | Weeks 24 / 48 of treatment |
| Subjects who achieve a reduction of at least 1 day per week of PS at Weeks 24 / 48 (CIC only). | Weeks 24 and 48 of treatment |
| Relative change from baseline in actual weekly PS volume at Weeks 12 / 24 / 48 (CIC only). | Weeks 12 / 24 / 48 of treatment |
| Subjects reaching enteral autonomy at Weeks 24 / 48 (CIC only). | Weeks 24 / 48 of treatment |
| At least 20% reduction of PS volume from baseline at Weeks 20 / 24. | Weeks 20 / 24 of treatment |
| Apparent clearance (CL/F) of apraglutide through population PK data analysis | Weeks 0 / 24 of treatment |
| Change from baseline on the Pittsburgh Sleep Quality Inventory (PSQI) at Weeks 24 / 48 (CIC only) | Weeks 24 / 48 of treatment |
| Change from baseline on the Patient Global Impression of Change (PGIC) at Weeks 24 / 48 (CIC only) | Weeks 24 / 48 of treatment. |
| Change from baseline on the Patient Global Impression of Treatment Satisfaction (PGI-TS) at week 24 and 48 (CIC only). | Weeks 24 / 48 of treatment |
| Change from baseline on the Patient Global Impression of Satisfaction with Parenteral Support (PGI-SPS) at Week 24 and 48 (CIC only). | Weeks 24 / 48 of treatment |
| Change from baseline on the Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and 48 (CIC only). | Weeks 24 / 48 of treatment |
| Absorption rate constant (ka) of apraglutide through population PK data analysis | Weeks 0 / 24 of treatment |
| Calorie reduction in the PN at Weeks 24. | Weeks 24 of treatment |
Countries
Argentina, Belgium, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Norway, Poland, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Outcome results
None listed