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 evaluate the long-term safety of glepaglutide treatment in short bowel syndrome (SBS) patients
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term efficacy of glepaglutide treatment in SBS patients - To evaluate the long-term immunogenicity of glepaglutide and its impact on pharmacokinetics (PK), efficacy, and safety in SBS patients - To evaluate quality of life for SBS patients treated with glepaglutide |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics Profile Sub-Study At Visit 7 (i.e. after 12 weeks of trial drug treatment), approximately 45 patients will be included in more extensive PK sampling. This is done to provide sufficient information about the PK-profile of glepaglutide and its primary active metabolites in SBS patients. The week prior to the PK sampling the patients must have been compliant to the planned dosing. The patients are planned to be from the lead-in trial from selected European sites. The aim is to include about 15 patients allocated to twice weekly and about 30 patients allocated to once weekly. The PK profile sub-study is optional and patients can participate in the main trial without participating in the sub-study. As each PK sample contains 2 mL of blood, this is resulting in additional 26 mL blood drawn for PK-profile purposes. The PK profile sub-study must start on a day of trial drug administration, and the vial must be taken after the first PK sampling (0 hour). |
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E.3 | Principal inclusion criteria |
The patient must meet all of the following inclusion criteria: - Signed informed consent Either of the following: - Completed the full treatment period of the lead-in trial (ZP1848-17111), regardless of treatment adherence. OR - Completed the Phase 2 trial (ZP1848-15073).
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E.4 | Principal exclusion criteria |
The patient must be excluded from this trial if any of the following criteria are met: - Withdrew consent from lead-in or Phase 2 trial. - Any condition, disease, or circumstance that in the Investigator's opinion would put the patient at any undue risk, prevent completion of the trial, or confounds planned assessments of the trial. - Use of GLP-1, GLP-2, human growth hormone (HGH), dipeptidyl peptidase-4 (DPP-4), citrulline, somatostatin, or analogs thereof within 3 months. Note: Prior glepaglutide trial drug is allowed. - Females of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant, or are not using highly effective contraceptive methods. Highly effective contraception methods and definition of child-bearing potential are described in Section 11.4.4 of there Study Protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints - Incidence and type of AEs (primary endpoint) - Incidence and type of serious adverse events (SAEs) and AESIs - Changes from baseline in: * Vital signs * Electrocardiogram (ECG) - Changes from baseline in: * Hematology * Biochemistry * Urinalysis - Immunogenicity
Efficacy Endpoints: - Reduction in weekly PS volume from baseline - Having at least 20% reduction in weekly PS volume from baseline - Reduction in days on PS ≥ 1 day/week from baseline - Reduction in weekly PS volume of 100% (weaned off)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be analyzed using the incidence of AEs occurring in each 3-month period for the first year; subsequent years will have longer periods assigned for analysis. All efficacy endpoints will be analyzed using average weekly results over the 3-month period between visits.
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: - Change in fluid composite effect (FCE) from baseline - Reduction in calculated energy content of parenteral macronutrients from baseline - Reduction in number of days on PS per week from baseline - Reduction of at least 40% in weekly PS volume from baseline
Other efficacy endpoints are: - Reduction in days on PS ≥ 2 days/week from baseline - Reduction in days on PS ≥ 3 days/week from baseline - Reduction in duration of PS infusions per week from baseline - Concentration trough levels of glepaglutide and metabolites - Change in plasma citrulline level from baseline - Change in weekly need for parenteral micronutrients (sodium, potassium, magnesium, and calcium) from baseline - Change in patient-reported outcomes (SBS-I and EQ-5D-5L) from baseline - Reduction in bowel movements or stoma bags emptying from baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Different dosage of the same product |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 |
Canada |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
United Kingdom |
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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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A patient will be considered as having completed the trial when: Patient completed EOT and Follow-up (FU)/Final Visit and patient interview, if consented (US, UK, DK, FR, DE sites only). |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |