E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049416 |
E.1.2 | Term | Short-bowel syndrome |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the efficacy of glepaglutide in reducing PS volume in SBS patients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of glepaglutide on other efficacy endpoints in patients with SBS. To evaluate the safety and tolerability of glepaglutide in patients with SBS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age ≥ 18 years and ≤ 90 years at Screening. •Diagnosis of SBS defined as remaining small bowel in continuity of estimated less than 200 cm [equal to 79 inches] and with the latest intestinal resection being at least 6 months prior to Screening and considered stable with regard to PS need. No restorative surgery planned in the trial period. •Requiring PS at least 3 days per week. •Willing to adhere to an individual pre-defined drinking menu during 48-hours measuring intervals. •Requiring PS at least 3 days per week and maintains a stable PS volume for at least 2 weeks. PS volume is considered stable if all of the criteria below are fulfilled: - Actual PS usage (volume and content) matches prescribed PS (± 10% deviation in volume is acceptable) - 48-hour urine volumes at 2 consecutive visits within a 2-week interval (± 4 days, i.e., visits should be 10 to 18 days apart) are similar (a maximum of ± 25% deviation is acceptable), while the oral fluid intake is constant (the two 48-hour oral intakes differ less than 10%) and maximum 3.5 L per day - Urine volume must be ≥ 1 L per day and ≤ 2.5 L per day
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E.4 | Principal exclusion criteria |
•More than 2 SBS-related or PS-related hospitalizations (e.g., catheter related bacteremia/sepsis, bowel obstruction, severe water-electrolytes disturbances, etc.) within 6 months prior to Screening. •Cardiac disease defined as: decompensated heart failure (New York Heart Association [NYHA] Class III-IV), unstable angina pectoris, and/or myocardial infarction within the last 6 months prior to Screening. •Any history of colon cancer. History of any other cancers (except margin-free resected cutaneous basal or squamous cell carcinoma or adequately treated in situ cervical cancer) unless disease-free state for at least 5 years. •Estimated creatinine clearance (CLcr; by the Cockcroft-Gault formula) < 30 mL/min. •Hepatic impairment defined as: - Total bilirubin ≥ 2 × the upper limit of normal (ULN), or - Aspartate aminotransferase (AST) ≥ 5 × ULN) - Alanine aminotransferase (ALT) ≥ 5× ULN •Use of GLP-1, GLP-2, human growth hormone (HGH), somatostatin, or analogs thereof, within 3 months prior to Screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical response, defined as achieving at least 20% reduction in weekly PS volume from baseline to both Weeks 20 and 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint(s) of evaluation are provided in section E.5.1 aside endpoints |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints: - Reduction in weekly PS volume from baseline to Week 24 - Increase in days off PS ≥ 1 day/week from baseline to Week 24 - Reduction of ≥ 20% in PS volume from baseline to both Weeks 12 and 24 - Reduction in weekly PS volume of 100% (weaned off) at Week 24 Secondary efficacy endpoints: - Change in fluid composite effect (FCE) from baseline to Week 24 - Reduction in calculated energy content of parenteral macronutrients from baseline to Week 24 - Reduction in number of days on PS per week from baseline to Week 24 - Reduction of ≥ 40% in PS volume from baseline to both Weeks 20 and 24 - PGIC improvement at Weeks 12, 20, and 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint(s) of evaluation are provided in section E.5.2 aside endpoints |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LSLV (EOT visit for patients who will continue participation in the Extension Trial or FU /Final Visit for patients who will not enter the Extension Trial) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 17 |