short bowel syndrome, intestinal failure (SBS-IF), colon-in-continuity (CIC) MedDRA version: 20.1 Level: PT Classification code 10049416 Term: Short-bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Sponsors
VectivBio AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Initial inclusion criteria (before baseline metabolic balance study) 1. Signed informed consent for this trial prior to any trial specific assessment 2. Male and female subjects with SBS-IF and CIC (at least 28% [Cummings, 1973] and no colostomy), receiving PS, secondary to surgical resection of the small intestine with <200 cm from duodenojejunal flexure, based on available medical/surgical records and with the latest intestinal resection being at least 12 months prior to Screening 3. Subject considered stable with regard to PS and weight. Stability is defined as a subject meeting all the following criteria in the 3 months preceding screening: a) Weight change (increase or decrease) =5% b) PS volume change not exceeding 25% c) PS energy content change not exceeding 25% d) Actual PS usage in terms of volume and content matches prescribed PS (±10%) 4. Parenteral support requirement of at least 2 days per week as assessed at Screening 5. Willingness to undergo either a colonoscopy or colonography and have any identified polyps removed via colonoscopy 6. Willingness to remain in clinic for metabolic study on three occasions for 5 days 7. Adhere to an individual pre-defined drinking menu and urine measurements during the 48-hour measuring periods 8. No planned restorative surgery or major intestinal surgery (more than 10% intestinal resection or surgery that changes anatomy group, i.e., stoma or CIC), in the trial period 9. Age =18 years at Screening 10.Women of childbearing potential must agree to practice effective contraception and to use a highly effective method of contraception during the trial and for 4 weeks after the EOT Visit. Such methods include one of the following: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; or a vasectomized partner. To be considered sterilized or infertile, females must have undergone surgical sterilization (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhea, without an alternative medical cause, may be confirmed with follicle-stimulating hormone test if there is doubt). Women who do not engage in heterosexual intercourse during the trial and 4 weeks after the EOT Visit will be allowed to join the trial without contraception following a thorough discussion with the Investigator to determine if this is feasible for the subject. The following methods are not considered acceptable methods of contraception: calendar, ovulation, symptothermal, post-ovulation methods, withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method 11.Male subjects with a female partner of childbearing potential must commit to practice methods of contraception (e.g., condoms or a vasectomy) and abstain from sperm donation during the trial and for 2 weeks after the EOT Visit. Their partners if they are women of childbearing potential must agree to practice contraception and to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); prog
Exclusion criteria
Exclusion criteria: 1. Pregnancy and/or lactation. 2. Body mass index equal or higher than 30 kg/m2 at the time of screening. 3. Major abdominal surgery (more than 10% intestinal resection) in the last 6 months prior to screening visit Surgery for feeding tube placement and cholecystectomy allowed. 4. A history of clinically significant intestinal adhesions which have not been treated surgically, increasing the risk of GI obstruction. 5. Constipation which is not adequately managed by dietary recommendations or laxatives 6. Active or untreated enterocutaneous fistula 7. History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within =5 years, except for adequately treated basal cell skin cancer 8. Acute cholecystitis or biliary obstruction left untreated within 1 month of Screening visit or during Screening period. 9. Subjects with active IBD or an underlying condition who require new drug treatment or regimen changes including increased dose of a previously administered treatment for at least the previous 6 months prior to Screening visit and during Screening period 10.Central venous catheter sepsis experienced within the previous 2 months, prior to Screening visit and during Screening period, or use of systemic antibiotics within the last 30 days, prior to Screening, due to catheter infection 11.Decompensated heart failure (New York Heart Association class III–IV) [NYHA] and/or known coronary heart disease defined as unstable angina pectoris and/or myocardial infarction within the previous 6 months prior to Screening 12.Radiation enteritis, scleroderma or residual evidence of intestinal dysmotility unrelated to SBS, including pseudo-obstruction and Hirschsprung's disease, and celiac disease, refractory or tropical sprue 13.History of alcohol and/or drug abuse within the previous 12 months prior to Screening 14.Child-Pugh score Class C 15.Elevated liver enzymes: a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x upper limit of normal (ULN) b) Alanine aminotransferase or AST >3 x ULN and total bilirubin >2 × ULN or international normalized ratio (INR) >1.5 for a person not using anticoagulant drug and INR >3 for a person on anticoagulant therapy such as warfarin c) Alanine aminotransferase or AST >3 x ULN and clinical signs of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia d) Subjects with serum conjugated bilirubin >34 µmol/L or 2 mg/dL during two consecutive measurements 16.Evidence of chronic renal disease as demonstrated by inadequate renal function as defined by estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology (CKD-EPI) formula at Screening visit 500 mL within 3 months prior to Screeni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of apraglutide in increasing intestinal energy absorption assessed by bomb calorimetry in relation to metabolic balance assessments.;Secondary Objective: • To evaluate fluid, electrolytes and macronutrients absorption indicative of clinical efficacy • To evaluate the efficacy of apraglutide in reducing the administered volume per week of PS from baseline • To evaluate the safety and tolerability of apraglutide • To assess apraglutide plasma concentrations to inform the PopPK model • To evaluate citrulline plasma concentrations to inform the PopPK / pharmacodynamic (PD) analysis;Primary end point(s): Change in absolute energy absorption over metabolic balance periods from baseline to Week 48;Timepoint(s) of evaluation of this end point: At week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: As per information provided in E.5.2. PK/PD related endpoints and Safety endpoints are being evaluated on an ongoing basis as per the study schedule given in the protocol.;Secondary end point(s): Efficacy endpoints related to PS volume • Relative change from baseline in actual weekly PS volume at Weeks 24 and 52 • Absolute change from baseline in actual weekly PS volume at Weeks 24 and 52 • Subjects who achieve a reduction of at least 1 day per week of PS from baseline at Weeks 24 and 52 • Clinical responders (20% reduction of PS volume from baseline) at Weeks 24 and 52 • Subjects reaching enteral autonomy at Weeks 24 and 52 • Energy reduction in the PN from baseline at Weeks 24 and 52 Efficacy endpoint related to nutritional, fluid (wet weight) and electrolyte absorption • Relative change in absorption of energy, over metabolic balance periods from baseline at Week 48 • Change in absorption of macronutrients, over metabolic balance periods from baseline at Week 48 • Change in absolute absorption of energy over metabolic balance periods from baseline at Week 4 • Change in absorption of macronutrients, over metabolic balance periods from baseline at Week 4 • Changes in urine output and urinary electrolytes (sodium, potassium, calcium and magnesium) over metabolic balance periods, from baseline at Week 4 and at Week 48 Patient reported outcomes • Changes from baseline in Pittsburgh Sleep Quality Inventory (PSQI) at Weeks 24 and 52 • Patient Global Impression of Change (PGIC) at Weeks 24 and 52 • Changes from baseline in Patient Global Impression of Treatment Satisfaction (PGI-TS) at Weeks 24 and 52 •Changes from baseline in Patient Global Impression of Satisfaction with Parenteral Support (PGI-SPS) at Weeks 24 and 52 • Changes from baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Weeks 24 and 52 PK/PD related endpoints • Trough plasma concentration (Ctrough) • Plasma citrulline levels Safety | — |
Countries
Denmark
Contacts
Public ContactClinical Trial Information Desk
VectivBio AG
Outcome results
None listed