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) and - 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, and - Urine volume is on average ≥ 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) |
Reduction in weekly PS volume from baseline to Week 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: Clinical response, defined as achieving at least 20% reduction in weekly PS volume from baseline to both Weeks 20 and 24 Reduction in days on PS ≥ 1 day/week from baseline to Week 24 Reduction in weekly PS volume from baseline to Week 12 Reduction in weekly PS volume of 100% (weaned off) at Week 24
Secondary efficacy endpoints: Reduction of at least 20% in PS volume from baseline to both Weeks 12 and 24 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 at least 40% in PS volume from baseline to both Weeks 20 and 24 PGIC improvement at Weeks 12, 20, and 24 Change in weight from baseline to Week 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
Canada |
United States |
Belgium |
Denmark |
France |
Germany |
Poland |
United Kingdom |
Netherlands |
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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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LVLS: A patient will be considered as having completed the trial when: - Patient completed EOT visit and exit interview, if consented (Danish, French, German, UK and US) and will continue participation in Extension Trial. - Patient completed Follow-up (FU)/Final Visit and exit interview, if consented (Danish, French, German, UK and US) and 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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 27 |