E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Clinical Study to Evaluate Mirikizumab in Pediatric Crohn’s Disease | Studio clinico per valutare Mirikizumab nella malattia di Crohn pediatrica | |
E.1.1.1 | Medical condition in easily understood language | Crohn’s Disease | Malattia di Crohn | |
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 | SOC | E.1.2 | Classification code | 10017947 | E.1.2 | Term | Gastrointestinal disorders | 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 evaluate whether treatment with IL-23 inhibitors is superior to adult placebo in achieving clinical remission and endoscopic response in pediatric participants with moderately to severely active CD at Week 52 who do not require modification of IP regimen, IP rescue therapy, or non-IP rescue therapy | Valutare se il trattamento con gli inibitori dell’IL-23 sia superiore al placebo degli adulti nell’ottenere una remissione clinica e una risposta endoscopica nei partecipanti pediatrici con MC in fase attiva da moderata a grave alla Settimana 52 che non richiedono una modifica del regime IP, terapia di soccorso con IP o terapia di soccorso senza IP | |
E.2.2 | Secondary objectives of the trial | To evaluate the efficacy of treatment with mirikizumab in achieving clinical response or clinical remission by PCDAI or CDAI at Week 12 | Valutare l’efficacia del trattamento con mirikizumab nel raggiungimento della risposta clinica o della remissione clinica secondo il PCDAI o il CDAI alla Settimana 12 | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1.Participants must have a diagnosis of CD or fistulizing CD, with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by clinical, endoscopic, and histologic criteria. 2.Participants must have moderately to severely active CD (as defined by a baseline PCDAI score >30). 3.Participants must have endoscopy with evidence of active CD defined as as SES-CD score =6 (or =4 for participants with isolated ileal disease) during screening into this study. 4.Participants must have a prior or current CD medication history that includes either inadequate response, loss of response to or failure to tolerate current treatment immunomodulators or with oral or IV corticosteroids or have received biologic therapy/JAK inhibitor for the treatment of CD and have a documented history of inadequate response, loss of response (LOR), or intolerance to the biologic therapy/JAK inhibitor. | 1. I partecipanti devono presentare una diagnosi di MC o MC fistolizzante, con colite, ileite o ileocolite attiva, confermata in qualsiasi momento in passato dai criteri clinici, endoscopici e istologici. 2. I partecipanti devono presentare MC in fase attiva da moderata a grave (come definito da un punteggio PCDAI al basale >30). 3. I partecipanti devono presentare endoscopia con evidenza di MC attiva definita come punteggio SES CD =6 (o =4 per i partecipanti con malattia ileale isolata) durante lo screening in questo studio. 4. I partecipanti devono presentare un’anamnesi pregressa o attuale di farmaci per la MC che includa una risposta inadeguata, una perdita della risposta o una mancata tolleranza dell’attuale trattamento con immunomodulatori o con corticosteroidi per via orale o EV oppure avere ricevuto una terapia biologica/inibitore di JAK per il trattamento della MC e presentare un’anamnesi documentata di risposta inadeguata, perdita della risposta (LOR) o intolleranza alla terapia biologica/inibitore di JAK. | |
E.4 | Principal exclusion criteria | 1. Participants must not have complications of CD such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestations that might be anticipated to require surgery. 2. Participants must not have an abscess. 3. Participants must not have any kind of bowel resection within 26 weeks or any other intra-abdominal surgery within 12 weeks of baseline. | 1. I partecipanti non devono presentare complicanze di MC come aderenze o stenosi sintomatiche, sindrome dell’intestino corto o qualsiasi altra manifestazione che si prevede possa richiedere un intervento chirurgico. 2. I partecipanti non devono avere un ascesso. 3. I partecipanti non devono essere sottoposti ad alcun tipo di resezione intestinale nelle 26 settimane o qualsiasi altro intervento chirurgico intra-addominale nelle 12 settimane precedenti il basale. | |
E.5 End points |
E.5.1 | Primary end point(s) | 1.Percentage of Participants with Clinical Response by Pediatric Crohn's Disease Activity Index (PCDAI) at Week 12 and Endoscopic Response by Simple Endoscopic Score for CD (SES-CD) at Week 52 [ Time Frame: Baseline to Week 52 ] Clinical response based on PCDAI, and endoscopic response based on SES-CD 2.Percentage of Participants with a Clinical Response by PCDAI at Week 12 and Clinical Remission by PCDAI at Week 52 [ Time Frame: Baseline to Week 52 ] Clinical response based on PCDAI, and clinical remission based on PCDAI | 1. Percentuale di partecipanti con risposta clinica in base all’Indice di attività della malattia di Crohn in età pediatrica (PCDAI) alla Settimana 12 e risposta endoscopica tramite punteggio endoscopico semplice per la MC (SES-CD) alla Settimana 52 [Intervallo di tempo: dal basale alla Settimana 52] Risposta clinica basata sul PCDAI e risposta endoscopica basata sul SES-CD 2. Percentuale di partecipanti con risposta clinica secondo il PCDAI alla Settimana 12 e remissione clinica secondo il PCDAI alla Settimana 52 [Intervallo di tempo: dal basale alla Settimana 52] Risposta clinica in base al PCDAI e remissione clinica in base al PCDAI | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | |
E.5.2 | Secondary end point(s) | 1.Percentage of Participants Achieving Clinical Response by PCDAI [ Time Frame: Week 12 ] Clinical response based on PCDAI 2.Percentage of Participants Achieving Clinical Response by Clinical Disease Activity Index (CDAI) [ Time Frame: Week 12 ] Clinical response based on CDAI for participants =12 years of age 3.Percentage of Participants Achieving Clinical Remission by PCDAI [ Time Frame: Week 12 ] Clinical remission based on PCDAI 4.Percentage of Participants Achieving Clinical Remission by CDAI [ Time Frame: Week 12 ] Clinical remission based on CDAI for participants =12 years of age 5.Percentage of Participants Achieving Endoscopic Response by SES-CD [ Time Frame: Week 12 ] Endoscopic response based on SES-CD 6.Percentage of Participants Achieving Clinical Response by PCDAI at Week 12 and Endoscopic Remission by SES-CD at Week 52 [ Time Frame: Baseline to Week 52 ] 7.Change from Baseline in C-reactive Protein (CRP) [ Time Frame: Baseline, Week 12 ] 8.Change from Baseline in CRP [ Time Frame: Baseline, Week 52 ] 9.Change from Baseline in Fecal calprotectin [ Time Frame: Baseline, Week 12 ] 10.Change from Baseline in Fecal calprotectin [ Time Frame: Baseline, Week 52 ] 11.Percentage of Participants Achieving Clinical Response PCDAI at Week 12 and Clinical Remission by CDAI at Week 52 [ Time Frame: Baseline to Week 52 ] Clinical response by PCDAI, CDAI for participants =12 years of age 12.Percentage of Participants Achieving Endoscopic Response [ Time Frame: Week 52 ] Endoscopic response by SES-CD 13.Percentage of Participants Achieving Clinical Remission by PCDAI [ Time Frame: Week 52 ] Clinical remission based on PCDAI 14.Percentage of Participants Achieving Clinical Response by PCDAI at Week 12 and PCDAI Clinical Remission without the use of Corticosteroids and who did not have Crohn's disease (CD)-Related Surgery at Week 52 [ Time Frame: Baseline to Week 52 ] Clinical response and clinical remission by PCDAI 15.Pharmacokinetics (PK): Clearance of Mirikizumab [ Time Frame: Baseline through Week 52 ] 16.Pharmacokinetics (PK): Volume of Distribution of Mirikizumab [ Time Frame: Baseline through Week 52 ] ; 1. Percentuale di partecipanti che ottengono una risposta clinica secondo PCDAI [Intervallo di tempo: Settimana 12] Risposta clinica in base al PCDAI 2. Percentuale di partecipanti che ottengono una risposta clinica in base all’Indice di attività della malattia clinica (CDAI) [Intervallo di tempo: Settimana 12] Risposta clinica basata sul CDAI per i partecipanti di età =12 anni 3. Percentuale di partecipanti che ottengono la remissione clinica in base al PCDAI [Intervallo di tempo: Settimana 12] Remissione clinica in base al PCDAI 4. Percentuale di partecipanti che ottengono la remissione clinica in base al CDAI [Intervallo di tempo: Settimana 12] Remissione clinica basata sul CDAI per partecipanti di età =12 anni 5. Percentuale di partecipanti che ottengono una risposta endoscopica in base al SES-CD [Intervallo di tempo: Settimana 12] Risposta endoscopica in base SES-CD 6. Percentuale di partecipanti che ottengono la risposta clinica in base al PCDAI alla Settimana 12 e la remissione endoscopica in base al SES-CD alla Settimana 52 [Intervallo di tempo: dal basale alla Settimana 52] 7. Variazione dal basale nella proteina C-reattiva (CRP) [Intervallo di tempo: Basale, Settimana 12] 8. Variazione dal basale nella CRP [Intervallo di tempo: Basale, Settimana 52] 9. Variazione dal basale nella calprotectina fecale [Intervallo di tempo: Basale, Settimana 12] 10. Variazione dal basale nella calprotectina fecale [Intervallo di tempo: Basale, Settimana 52] 11. Percentuale di partecipanti che ottengono una risposta clinica in base al PCDAI alla Settimana 12 e remissione clinica in base al CDAI alla Settimana 52 [Intervallo di tempo: dal basale alla Settimana 52] Risposta clinica in base al PCDAI, CDAI per i partecipanti di età =12 anni 12. Percentuale di partecipanti che ottengono la risposta endoscopica [Intervallo di tempo: Settimana 52] Risposta endoscopica in base al SES-CD 13. Percentuale di partecipanti che ottengono la remissione clinica in base al PCDAI [Intervallo di tempo: Settimana 52] Remissione clinica in base al PCDAI 14 Percentuale di partecipanti che ottengono la risposta clinica in base al PCDAI alla Settimana 12 e la remissione clinica in base al PCDAI senza l’uso di corticosteroidi e che non sono stati sottoposti a intervento chirurgico connesso alla malattia di Crohn alla Settimana 52 [Intervallo di tempo: dal basale alla Settimana 52] Risposta clinica e remissione clinica in base al PCDAI 15. Farmacocinetica (PK): Clearance di mirikizumab [Intervallo di tempo: dal basale alla fine della Settimana 52] 16. Farmacocinetica (PK): Volume di distribuzione di mirikizumab [Intervallo di tempo: dal basale alla fine della Settimana 52] | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | |
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 | No |
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | |
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 | 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 | 35 |
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 | Information not present in EudraCT |
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 | Australia | Brazil | Canada | Israel | Japan | Korea, Republic of | United States | Austria | France | Poland | Netherlands | Spain | Switzerland | Czechia | Italy | Belgium | Norway | Portugal | United Kingdom | |
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 | LPLV for this ISA | Ultima visita ultimo paziente per questa ISA | |
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 | 0 |
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 |