| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of celiac disease |
| Leczenie celiakii |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inflammation in the small intestine |
| Zapalenie jelita cienkiego |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007864 |
| E.1.2 | Term | Celiac disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To assess 3 different doses and 2 different dosing schedules of ZED1227 capsules for efficacy in:
- Improvement of the duodenal mucosal morphology as measured by morphometry (VH:CrD), and
- Improvement of celiac disease symptoms assessed by Celiac Disease Symptom Diary (CDSD) in celiac disease subjects experiencing symptoms and having mucosal damage despite gluten-free diet. |
Ocena 3 różnych dawek i 2 różnych schematów dawkowania kapsułek ZED1227 pod kątem skuteczności w:
- Poprawy morfologii błony śluzowej dwunastnicy mierzonej za pomocą morfometrii (VH:CrD), oraz.
- Poprawę objawów celiakii ocenianych za pomocą Celiac Disease Symptom Diary (CDSD) u osób z celiakią doświadczających objawów i mających uszkodzenie błony śluzowej pomimo stosowania diety bezglutenowej. |
|
| E.2.2 | Secondary objectives of the trial |
To assess efficacy of ZED1227 capsules for
• Improvement and changes of duodenal mucosal morphology as measured by morphometry (VH:CrD),
• Improvement and changes of celiac disease symptoms assessed by CDSD,
• Improvement in the Marsh-Oberhuber grouped classes
• Changes of inflammatory cell subsets in duodenal biopsies,
• Changes in serum markers of celiac inflammation,
• Safety and tolerability in terms of adverse events and laboratory parameters,
• Subjects’ quality of life. |
Ocena skuteczności kapsułek ZED1227 w zakresie
- Poprawa i zmiany morfologii błony śluzowej dwunastnicy mierzonej morfometrią (VH:CrD),
- Poprawy i zmian objawów celiakii ocenianych za pomocą CDSD,
- Poprawa w zakresie klas zgrupowanych Marsh-Oberhuber
- Zmiany podzbiorów komórek zapalnych w biopsjach dwunastnicy,
- Zmiany markerów zapalenia w celiakii w surowicy krwi,
- Bezpieczeństwo i tolerancja w zakresie zdarzeń niepożądanych i parametrów laboratoryjnych,
- Jakość życia uczestników badania. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Documented initial biopsy proven diagnosis of celiac disease or, in
case of missing histological documentation, TG2-IgA > 10 x upper limit
of normal (ULN) at diagnosis at least 12 months prior to V0
•Adherence to a gluten-free diet (GFD) for at least 12 months prior to V0
•Human leukocyte antigen DQ (HLA-DQ) typing compatible with celiac disease
•At least one moderate or severe gastrointestinal symptom (i.e., diarrhoea, abdominal pain, bloating or nausea) during the last 4 weeks prior to Baseline Visit
•Negative diagnosis of Helicobacter pylori infection
|
|
| E.4 | Principal exclusion criteria |
1.Presence of hypo- or hyperthyroidism. A patient with a thyroid stimulating hormone (TSH) level up to 25% higher than ULN or up to 25% lower than the lower limit of normal (LLN) but with normal free
triiodothyronine (FT3) and free thyroxine (FT4) levels can be included in the trial. In addition, a patient with a well-controlled thyroid disorder during the previous 3 months can be included,
2.Subjects diagnosed to have confirmed refractory celiac disease type I (RCDI) or II (RCDII), with the exception that patients with a diagnosis of RCDI can be considered for inclusion if they do not have clear signs of T cell monoclonality or atypical T cells (e.g., as revealed by CD3/CD8 IHC) and if they do not present with very severe symptoms and/or parameters of significant malabsorption and if they have not received prior treatment with immunosuppressants such as budesonide or
azathioprine,
3.Severe complications of celiac disease [e.g., enteropathy associated Tcell lymphoma (EATL), ulcerative jejunitis, perforation],
4.Concomitant diseases of the intestinal tract in addition to celiac disease, such as Crohn's disease, ulcerative colitis, other forms of inflammatory bowel disease, severe irritable bowel syndrome,
microscopic colitis, small intestinal bacterial overgrowth (SIBO), exocrine pancreatic insufficiency; any other active diseases of the intestinal tract (e.g., active, untreated peptic ulcer, esophagitis,
gastroesophageal reflux disease) that might, in the investigator's opinion, interfere with assessment of symptoms of abdominal pain, diarrhoea, or other components of celiac disease, 5.History or presence of dermatitis herpetiformis, 6. History or presence of neurological disorders like ataxia or neuropathy (mild neuropathy, related or unrelated to celiac disease, is not a reason for exclusion), 7.Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder or other disease, which in the opinion of the investigator might have an influence on the subject's compliance or the interpretation of the results, 8.Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Patients with basal cell carcinoma of the skin completely resected can be included, 9.Evidence of relevant systemic disease,10.Abnormal hepatic function (ALT or ALP > 2.5 x ULN), liver cirrhosis, or portal hypertension,11.Glomerular filtration rate ≤ 60 ml/min/1.73 m², 12.Continuous intake of systemic (oral or intravenous) corticosteroids or immunomodulators (e.g., glucocorticoids, cyclosporine, methotrexate, anti-TNF- therapy, anti-integrin therapy, Janus kinase inhibitors), high dose inhaled corticosteroids (> 1000 µg/d of beclomethasone dipropionate or equivalent) during the past 3 months before V0, 13.Continuous intake of drugs with suspicion of impact on villous atrophy, such as •proton-pump inhibitors (PPIs; permitted at a regular dose equivalent to 20-40 mg/day pantoprazol, esomeprazole or equivalent), •selective serotonin reuptake inhibitors [SSRIs1; low to medium dose (10-150 mg Fluvoxamine or equivalent dose of other SSRIs) permitted in case of long-term therapy (at least for 6 months)], •losartan (angiotensin II receptor blockers equivalent to 50 mg losartan permitted except for olmesartan forbidden at any dose), and •mycophenolate2,3 (forbidden at any dose) during the past 2 months before biopsy sampling in Trial Period A; •non-steroidal anti-inflammatory drugs (NSAIDs; maximal daily dose permitted 900 mg for ibuprofen, 500 mg for naproxen and 75 mg for diclofenac, except for one week before biopsy) and •acetylsalicylic acid (max daily dose permitted 100 mg) during the past 4 weeks before biopsy sampling in Trial Period A, 14. Regular excessive alcohol abuse (> 12 g/d for women, > 24 g/d formen) within the past 12 months before V0, 15.Patients receiving dual antiplatelet therapy [i.e., acetylsalicylic acid in combination with thienopyridines (clopidogrel, prasugrel, ticlopidine or ticagrelor)] or oral anticoagulants (i.e., warfarin, dabigatran, etexilate, rivaroxaban, apixaban), 16.Unwillingness to undergo upper gastrointestinal endoscopy with biopsy in trial period A and at Final/Withdrawal Visit, 17.Known intolerance/hypersensitivity/resistance to IMP and excipients or drugs of similar chemical structure or pharmacological profile, 18.Doubt about the subject's cooperation, e.g., because of addiction to alcohol or drugs, 19.Existing or intended pregnancy or breast-feeding, 20.Close affiliation with the investigator (e.g., a close relative) or persons working at the study sites or subject who is an employee of the Sponsor's company, 21.Subjects who are institutionalised because of legal or regulatory order, 22. Participation in another clinical trial and having received IMP within the last 30 days prior to V0 or within 5 half-lives of IMP, simultaneous participation in another clinical intervention trial, or previous participation in this trial and having received IMP. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Multi-component endpoint:
-improvement of intestinal mucosal morphology
-improvement in Non-Stool GI Specific Symptom Score OR as an improvement in Diarrhoea Severity Score
|
Wielo komponentowy punkt końcowy:
-poprawa morfologii błony śluzowej jelita.
-poprawa w Non-Stool GI Specific Symptom Score LUB jako poprawa w Diarrhoea Severity Score |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks, from Baseline Visit B1 (week 5) to Visit 7 (week 17) |
12 tygodni, od wizyty podstawowej B1 (tydzień 5) do wizyty 7 (tydzień 17).
|
|
| E.5.2 | Secondary end point(s) |
• Improvement of intestinal mucosal morphology
• Changes in intestinal mucosal morphology
• Changes in Patient Reported Outcomes (PRO)
• Change in health-related quality of life (EQ-5D-5L)
• Change in serological markers |
- Poprawa morfologii błony śluzowej jelita
- Zmiany w morfologii błony śluzowej jelita
- Zmiany w wynikach badań zgłaszanych przez pacjentów (PRO)
- Zmiana w jakości życia związanej ze zdrowiem (EQ-5D-5L)
- Zmiana markerów serologicznych |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks, from Baseline Visit B1 (week 5) to Visit 7 (week 17) |
| 12 tygodni, od wizyty podstawowej B1 (tydzień 5) do wizyty 7 (tydzień 17). |
|
| 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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient-reported outcome (=PRO) |
| Wynik oceniany przez pacjenta (=PRO) |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 4 |
| 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 103 |
| 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 |
| New Zealand |
| Switzerland |
| Bosnia and Herzegovina |
| North Macedonia |
| Australia |
| Serbia |
| Austria |
| Bulgaria |
| Croatia |
| Estonia |
| Finland |
| France |
| Germany |
| Ireland |
| Italy |
| Lithuania |
| Norway |
| Poland |
| Romania |
| Spain |
| Sweden |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| LVLS |
| Ostatnia wizyta ostatniego pacjenta |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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