E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of celiac disease |
Tratamiento de la enfermedad celíaca |
|
E.1.1.1 | Medical condition in easily understood language |
Inflammation in the small intestine |
Inflamación en el intestino delgado |
|
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 | 100000004856 |
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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. |
Evaluar la eficacia de 3 dosis y 2 calendarios de dosificación diferentes de las cápsulas de ZED1227 en: • mejora de la morfología de la mucosa duodenal medida por morfometría (VH:CrD), y • mejora de los síntomas de la enfermedad celíaca evaluados con ayuda del diario de síntomas de la celiaquía (Celiac Disease Symptom Diary, CDSD) en sujetos con enfermedad celíaca que experimentan síntomas y presentan daños en la mucosa a pesar de seguir una dieta sin gluten. |
|
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. |
Evaluar la eficacia de las cápsulas de ZED1227 en cuanto a: • mejora y cambios de la morfología de la mucosa duodenal medidos por morfometría (VH:CrD), • mejora en las clases agrupadas de Marsh-Oberhuber, • mejora y cambios de los síntomas de la enfermedad celíaca evaluados con ayuda del CDSD, • cambios en los subconjuntos de células inflamatorias en las biopsias duodenales, • cambios en los marcadores séricos de la inflamación celíaca, • seguridad y tolerabilidad en términos de acontecimientos adversos y parámetros de laboratorio, • calidad de vida de los sujetos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Documented initial biopsy proven diagnosis of celiac disease 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 |
-Diagnóstico inicial documentado de enfermedad celíaca mediante biopsia al menos 12 meses antes de la V0 -Cumplimiento de una dieta sin gluten (GFD) durante al menos 12 meses antes de la V0 -Tipificación del antígeno leucocitario humano DQ (HLA-DQ) compatible con la enfermedad celíaca -Al menos un síntoma gastrointestinal moderado o grave (es decir, diarrea, dolor abdominal, hinchazón o náuseas) durante las últimas 4 semanas antes de la visita inicial -Diagnóstico negativo de infección por Helicobacter pylori |
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E.4 | Principal exclusion criteria |
•Selective immunoglobulin A deficiency •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 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 •Severe complications of celiac disease •Any concomitant diseases of the intestinal tract in addition to celiac disease that might, in the investigator's opinion, interfere with assessment of symptoms of abdominal pain, diarrhea, or other components of celiac disease •Evidence of relevant systemic disease |
-Deficiencia selectiva de inmunoglobulina A -Sujetos con diagnóstico de enfermedad celíaca refractaria confirmada tipo I (RCDI) o II (RCDII), con la excepción de que los pacientes con diagnóstico de RCDI pueden ser considerados para su inclusión si no tienen signos claros de monoclonalidad de células T o células T atípicas y si no presentan síntomas muy graves y/o parámetros de malabsorción significativa y si no han recibido tratamiento previo con inmunosupresores como budesonida o azatioprina -Complicaciones graves de la enfermedad celíaca -Cualquier enfermedad concomitante del tracto intestinal además de la enfermedad celíaca que pudiera, a juicio del investigador, interferir en la evaluación de los síntomas de dolor abdominal, diarrea u otros componentes de la enfermedad celíaca -Evidencia de enfermedad sistémica relevante |
|
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 |
Punto final multicomponente: -mejora de la morfología de la mucosa intestinal -mejora en la puntuación de los síntomas específicos no gastrointestinales o como mejora en la puntuación de la gravedad de la diarrea |
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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 semanas, desde la visita inicial B1 (semana 5) hasta la visita 7 (semana 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 |
- Mejora de la morfología de la mucosa intestinal - Cambios en la morfología de la mucosa intestinal - Cambios en los resultados comunicados por los pacientes (PRO) - Cambio en la calidad de vida relacionada con la salud (EQ-5D-5L) - Cambio en los marcadores serológicos |
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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 semanas, desde la visita inicial B1 (semana 5) hasta la visita 7 (semana 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) |
|
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 | 4 |
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 |
Austria |
Estonia |
Finland |
France |
Lithuania |
Poland |
Sweden |
Bulgaria |
Romania |
Spain |
Switzerland |
Germany |
Italy |
Bosnia and Herzegovina |
Croatia |
Ireland |
North Macedonia |
Norway |
Serbia |
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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 |
Última visita del último paciente |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |