E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis |
Colite Ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis is a type of inflammatory bowel disease that causes the lining of the large intestine (colon) to become inflamed (irritated and swollen) which may cause ulcers and bleeding |
La Colite Ulcerosa è un tipo di malattia infiammatoria intestinale che provoca infiammazione (irritazione e gonfiore) del rivestimento dell’intestino crasso(colon) e può causare ulcere e sanguinamenti |
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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 | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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 compare the efficacy of brazikumab with that of placebo to achieve clinical remission |
• Confrontare l'efficacia di brazikumab con quella del placebo nell'ottenere la remissione clinica |
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E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of brazikumab with that of placebo to achieve sustained clinical remission • To compare the efficacy of brazikumab with that of placebo to achieve corticosteroid-free (CS-free) clinical remission • To evaluate the pharmacokinetics (PK) and immunogenicity of brazikumab in participants with UC • To characterize the exposure-response relationships of brazikumab |
• Confrontare l'efficacia di brazikumab con quella del placebo nell'ottenere la remissione clinica prolungata • Confrontare l'efficacia di brazikumab con quella del placebo nell'ottenere la remissione clinica libera da corticosteroidi (CS-free) • Valutare la farmacocinetica (PK) e l'immunogenicità di brazikumab nei partecipanti affetti da UC • Caratterizzare le relazioni esposizione-risposta di brazikumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent prior to any study procedures and willing and able to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period. 2. Aged 18 to 80 years of age, inclusive, at screening. 3. Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to screening as determined by the investigator based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings. 4. Evidence of UC extending proximal to the rectum (= 15 cm of involved colon). 5. Moderately to severely active UC as defined by Stool Frequency and Rectal Bleeding subscores and Modified Mayo endoscopic subscore. 6. Participant had an inadequate, failed response, or intolerance to intervention with oral corticosteroids, azathioprine, methotrexate, or 6-mercaptopurine, or demonstrated corticosteroid dependence for the treatment of ulcerative colitis. 7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception. |
1. Capacità di fornire consenso informato scritto prima di qualsiasi procedura dello studio e volontà e capacità di presentarsi a tutte le visite di studio, attenersi alle procedure di studio, leggere e scrivere al fine di completare i questionari, e capacità di completare il periodo di studio. 2. Età compresa tra 18 e 80 anni, inclusi, allo screening. 3. Diagnosi di CU con insorgenza dei sintomi da un minimo di 3 mesi prima dello screening come determinato dallo Sperimentatore in base a anamnesi, esclusione di cause infettive, e caratteristici finding endoscopici e istologici. 4. Evidenza di CU con estensione prossimale al retto (= 15 cm di colon coinvolto). 5. CU da moderatamente a gravemente attiva come definito dai sotto-punteggi Stool Frequency and Rectal Bleeding e sotto-punteggio endoscopico Modified Mayo. 6. Il participante ha avuto una risposta, inadeguata o fallita, o una intolleranza al trattamento con corticosteroidi orali, azatioprina, metotrexato, o 6-mercaptopurina, o dipendenza da corticosteroidi dimostrata per il trattamento della colite ulcerosa. 7. Le donne in grado di procreare che sono sessualmente attive con un partner non sterilizzato, devono usare 2 metodi contraccettivi accettabili. |
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E.4 | Principal exclusion criteria |
1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge) 2. History of fulminant colitis, a diagnosis of Crohn's disease or indeterminate colitis, presence or history of a fistula consistent with Crohn's disease, primary sclerosing cholangitis, celiac disease, or bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening. 3. History of subtotal colectomy with ileorectostomy or colectomy with ileonal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months. 4. Participant has received the following treatment: - Infliximab: within 8 weeks prior to Baseline (Visit 2) - Adalimumab, certolizumab pegol, or golimumab: within 10 weeks prior to Baseline (Visit 2) - Vedolizumab within 18 weeks prior to Baseline (Visit 2) - Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Baseline (Visit 2) 5. Participant has previously received vedolizumab, and was intolerant to intervention or had met the criteria for primary or secondary non-response to intervention. 19. Participant is pregnant, breastfeeding, or plans to become pregnant during the study. |
1. Il participante ha CU limitata al retto (ovvero, non oltre 15 cm dal margine anale) 2. Anamnesi di colite fulminante, diagnosi di malattia di Crohn o colite indeterminata, presenza o anamnesi di una fistola compatibile con malattia di Crohn, colangite sclerosante primitiva, malattia celiaca o malassorbimento degli acidi biliari. I participanti con anamnesi di megacolon tossico entro 12 mesi da screening. 3. Anamnesi di colectomia subtotale con ileorettostomia o colectomia con pouch ileoanale, Koch pouch, ileostomia o altra pregressa resezione del colon, o anticipata necessità di intervento chirurgico per il controllo della CU entro 6 mesi. 4. Il participante ha ricevuto il seguente trattamento: - Infliximab: entro 8 settimane prima del Baseline (Visita 2) - Adalimumab, certolizumab pegol o golimumab: entro 10 settimane prima del Baseline (Visita 2) - Vedolizumab entro 18 settimane prima del Baseline (Visita 2) - Altri farmaci proibiti, trattamento biologico o piccolo molecule entro 5 emivite priam del Baseline (Visita 2) 5. Il participante ha ricevuto in precedenza vedolizumab ed era stato intollerante al trattamento o è rientrato nei criteri per la non-risposta primaria o secondaria al trattamento. 19. La participante è incinta, in allattamento o pianifica di iniziare una gravidanza durante lo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission: - modified Mayo Score (mMS) at Week 10: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 |
Remissione clinica: - Mayo Score modificato (mMS) alla Settimana 10: subscore Endoscopico = 0 o 1, E subscore Sanguinamento rettale = 0, E subscore Frequenza feci = 0 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Stool frequency - Visit 1 through Follow-up 2 (e-diary) Rectal bleeding - Visit 1 through Follow-up 2 (e-diary) Findings of endoscopy - Visits 1, 6, 17 Physician's global assessment - Visits 1, 6, 17 Each individual item assessed on 0-3 ordinal scale described in Mayo Scoring System for Assessment of Ulcerative Colitis Activity. |
Items del Mayo score Frequenza feci - da Visita 1 fino a Follow-up 2 (e-diario) Sanguinamento rettale - da Visita 1 fino a Follow-up 2 (e-diario) Rilievi dell’endoscopia - Visite 1, 6, 17 Valutazione globale del medico - Visite 1, 6, 17 Ogni singolo item è valutato su una scala ordinale 0-3 descritta nel Mayo Scoring System for Assessment of Ulcerative Colitis Activity. |
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E.5.2 | Secondary end point(s) |
1. Sustained clinical remission: - mMS at both Week 10 and Week 54: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 2. CS-free clinical remission: - mMS at Week 54 for participants who are CS-free for at least the last 12 weeks before the assessment at Week 54: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 3. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies 4. Exposure-response model linking primary endpoints to metrics of model-predicted individual brazikumab exposures |
1. Remissione clinica prolungata: - mMS alla Settimana 10 e alla Settimana 54: subscore Endoscopico = 0 o 1, E subscore Sanguinamento rettale = 0, E subscore Frequenza feci = 0 2. Remissione clinica libera da corticosteroidi (CS-free): - mMS alla Settimana 54 per I partecipanti che sono CS-free per almeno le ultime 12 settimane prima della valutazione alla Settimana 54: subscore Endoscopico = 0 o 1, E subscore Sanguinamento rettale = 0, E subscore Frequenza feci = 0 3. Modello PK di popolazione delle concentrazioni sieriche di brazikumab e analisi per gli anticorpi sierici anti-brazikumab 4. Modello esposizione-risposta che collega gli endpoint primari alle metriche delle esposizioni a brizikumab individuali predette dal modello |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
as listed above |
come sopra elencato |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Blood and stool samples will be collected and analyzed to evaluate protein, nucleic acid, and cellular biomarkers, optional blood sample for genetic research |
Campioni di sangue e di feci saranno raccolti e analizzati per valutare proteine, acidi nucleici e biomarker cellulari, campione di sangue facoltativo per ricerca genetica |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
con doppio placebo |
Double dummy |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
Colombia |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Russian Federation |
Singapore |
South Africa |
Taiwan |
Turkey |
United States |
Belgium |
Czechia |
France |
Germany |
Hungary |
Italy |
Poland |
Romania |
Spain |
Switzerland |
United Kingdom |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |