E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis
Crohn¿s Disease |
Colite Ulcerosa Morbo di Crohn |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis
Crohn¿s Disease |
Colite Ulcerosa Morbo di Crohn |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 | 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 obtain data on long term safety and tolerability of vedolizumab SC in Ulcerative Colitis (UC) and Crohn¿s Disease (CD) subjects. |
¿ Ottenere dati sulla sicurezza e tollerabilit¿ a lungo termine riguardanti vedolizumab SC in soggetti affetti da CU e MC. |
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E.2.2 | Secondary objectives of the trial |
¿ To obtain data on adverse events of special interest (AESIs; serious infections including opportunistic infection such as PML, liver injury, malignancies, injection site reactions or systemic reactions and hypersensitivity) in UC and CD subjects receiving long-term vedolizumab SC treatment.
¿ To obtain data on maintaining clinical response and clinical remission in UC and CD subjects receiving long-term vedolizumab SC treatment.
¿ To obtain data on patient reported outcomes (PRO) in UC and CD subjects receiving long-term vedolizumab SC treatment.
¿ To obtain data on work productivity and activity impairment (WPAI-UC; WPAI-CD) in UC and CD subjects receiving long-term vedolizumab SC treatment.
¿ To obtain data on time to major UC and CD-related events (hospitalizations, bowel surgeries,
and procedures) in UC and CD subjects receiving long-term vedolizumab SC treatment. |
¿ Ottenere dati sugli eventi avversi gravi di particolare interesse in soggetti affetti da CU e MC sottoposti a trattamento a lungo termine con vedolizumab SC. ¿ Ottenere dati circa il mantenimento della risposta clinica e della remissione clinica in soggetti affetti da CU e MC sottoposti a trattamento ¿ Ottenere dati riguardo agli esiti riferiti dal paziente (PRO) in soggetti affetti da CU e MC sottoposti a trattamento a lungo termine con vedolizumab SC. ¿ Ottenere dati sulla compromissione dell¿attivit¿ e della produttivit¿ lavorativa in soggetti affetti da CU e MC sottoposti a trattamento ¿ Ottenere dati riguardo al tempo agli eventi maggiori correlati a CU e MC in soggetti affetti da CU e MC sottoposti a trattamento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has previously participated in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Subjects who withdraw early from Study MLN0002SC-3027 or MLN0002SC-3031 must have withdrawn due to treatment failure (ie, as determined by disease worsening or need for rescue medications from Week 14) during the Maintenance Period.
2. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance.
3. Subjects with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial Screening Visit of MLN0002SC-3027 or MLN0002SC-3031.
4. May be receiving a therapeutic dose of the following drugs provided that the dose has been stable throughout the qualifying double-blind study:
¿ Oral 5-ASA compounds.
¿ Oral corticosteroid therapy (prednisone or equivalent steroid at a dose =30 mg/day, budesonide at a dose =9 mg/day).
¿ Topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories.
¿ Probiotics (eg, Culturelle, Saccharomyces boulardii).
¿ Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
¿ Antibiotics used for treatment of IBD (ie, ciprofloxacin, metronidazole).
¿ Azathioprine or 6-mercaptopurine, provided the patient was receiving this medication during prior participation in Study MLN002SC-3027.
¿ Methotrexate, provided the patient was receiving this medication during prior participation
in Study MLN002SC-3031. |
1. In precedenza il soggetto ha preso parte allo studio MLN0002SC-1027 o allo studio MLN0002SC-3031, e, a giudizio dello sperimentatore, ha mostrato di tollerare bene il farmaco dello studio. I soggetti che si sono ritirati prematuramente dallo studio MLN0002SC-3027 o dallo studio MLN0002SC-3031 devono essersi ritirati a causa del mancato successo del trattamento (ossia come determinato dal peggioramento della malattia o dall’esigenza di farmaci di soccorso dalla Settimana 14 del rispettivo studio) nel corso del periodo di mantenimento. 2. I soggetti con anamnesi familiare di cancro del colon-retto, anamnesi personale di rischio aumentato di cancro del colon-retto, età =50 anni o altri fattori di rischio noti devono aver effettuato i contorlli previsti per il cancro del colon-retto. 3. I soggetti con colite estesa o pancolite da più di 8 anni o colite sinistra da più di 12 anni devono avere evidenza documentata che è stata effettuata una colonscopia di controllo entro 12 mesi dalla visita i screening iniziale per MLN0002SC-3027 o MLN0002SC-3031. 4. Può assumere una dose terapeutica dei seguenti farmaci a condizione che la dose sia stata stabile per tutto lo studio di qualificazione in doppio cieco: - Composti 5-ASA per via orale - Terapia a base di corticosteroidi orali (prednisone o steroide equivalente alla dose =30 mg/giorno, budesonide alla dose =9 mg/giorno). - Probiotici (ad es. Culturelle, Saccharomyces boulardii). - Antidiarroici (ad es. loperamide, difenossilato con atropina) per il controllo della diarrea cronica. - Antibiotici utilizzati per il trattamento della malattia infiammatoria intestinale (IBD) (ad es. ciprofloxacina, metronidazolo). - Azatioprina o 6-mercaptopurina, a condizione che il soggetto stesse assumendo questo farmaco durante la precedente partecipazione allo studio MLN002SC-3027 o MLN002SC-3031. - Metotrexato, a condizione che il soggetto stesse assumendo questo farmaco durante la precedente partecipazione allo studio MLN002SC-3031 5. In precedenza il soggetto ha preso parte allo studio MLN0002SC-3027 o allo studio MLN0002SC-3031, e, a giudizio dello sperimentatore, ha mostrato di tollerare bene il farmaco dello studio. Sono idonei alla partecipazione i soggetti che non avevano ottenuto una risposta clinica alla Settimana 6 e non erano stati randomizzati alla Fase di mantenitmento, ma hanno ottenuto una risposta clinica alla Settimana 14 dopo aver ricevuto una terza infusione EV di vedolizumab in aperto. |
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E.4 | Principal exclusion criteria |
1. The subject required surgical intervention for IBD during or after participation in Study MLN0002SC-3027 or MLN0002SC-3031, currently requires surgical intervention for IBD, or is anticipated to require surgical intervention for IBD during this study.
2. The subject has had previous exposure to approved or investigational anti-intergins (eg, natalizumab, efalizumab, etrolizumab, AMG 181) or anti-MAdCAM1 antibodies or rituximab.
3. The subject has had hypersensitivity to any of the vedolizumab excipients.
4. Any live vaccinations within 30 days prior to vedolizumab SC administration.
5. The subject has developed a chronic or severe infection, or, any new, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder during or after participation in a prior vedolizumab study that, in the opinion of the investigator, would confound the study results or compromise subject safety.
6. The subject has withdrawn from Study MLN0002SC-3027 or MLN0002SC-3031due to a study-drug related AE.
7. The subject is unwilling or unable to self inject, or does not have a caregiver (defined as a legal adult) to inject the study medication.
8. The subject has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to enrollment. Subjects with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment.
9. The subject has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or demylinating neurodegenerative disease.
10. The subject has a positive PML subjective symptom checklist prior to the administration of study drug. |
• Il soggetto necessita di intervento chirurgico per malattia infiammatoria intestinale (Inflammatory Bowel Disease, IBD) durante o dopo la partecipazione allo studio MLN0002SC-3027 o allo studio MLN0002SC-3031, al momento necessita di intervento chirurgico per IBD oppure si prevede necessiti di intervento chirurgico per IBD nel corso del presente studio. • Il soggetto si è ritirato dallo studio MLN0002SC-3027 o dallo studio MLN0002SC-3031 per via di un evento avverso (EA) correlato al farmaco.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Subject year adjusted treatment emergent-related AEs and SAEs during long-term vedolizumab SC treatment. |
- Eventi avversi (EA) ed eventi avversi seri (SAE) emergenti dal trattamento corretti per soggetti all'ano durante il trattamento a lungo termine con vedlizumab SC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.
AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit. |
La registrazione degli eventi avversi (EA) inizierà dal momento della prima somministrazione del farmaco dello studio (Settimana 0), La normale registrazione degli eventi avversi (EA) continuerà fino a 18 settimane dopo l'ultima dose del farmaco. |
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E.5.2 | Secondary end point(s) |
¿ Subject year adjusted AESIs during long-term vedolizumab SC treatment.
¿ Proportion of subjects with clinical response during long-term vedolizumab SC treatment using partial Mayo scores in UC subjects and Harvey-Bradshaw Index (HBI) scores in CD subjects.
¿ Proportion of subjects with clinical remission during long-term vedolizumab SC treatment using partial Mayo scores in UC subjects and Harvey-Bradshaw Index (HBI) scores in CD subjects. |
• Eventi avversi di nteresse speciale (AESI) corretti per soggetti all’anno durante il trattamento a lungo termine con vedolizumab SC. • Percentuale di soggetti con risposta clinica durante il trattamento a lungo termine con vedolizumab SC utilizzando i punteggi Mayo parziali (definita come riduzione del punteggio Mayo parziale di 2 punti e 25% rispetto al basale con simultanea diminuzione del punteggio di sanguinamento rettale di 1 o sottopunteggio di sanguinamento rettale assoluto di 1) nei soggetti con CU e i punteggi dell’indice di Harvey-Bradshaw (HBI) (definita come riduzione del punteggio HBI di 3 punti rispetto al basale) nei soggetti con MC. • Percentuale di soggetti con remissione clinica durante 1 trattamento a lungo termine con vedolizumab SC utilizzando i punteggi Mayo parziali (definita come punteggio Mayo parziale di 2 e nessun sottopunteggio individuale >1 punto) nei soggetti con CU e i punteggi dell’indice di Harvey-Bradshaw (HBI) (definita come punteggio HBI di 4 punti) nei soggetti con MC. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.
AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Disease activity (Mayo/HBI):
QW and Q2W: Weeks 0, 4, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit. |
Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.
AE/SAE assessments: QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit. Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Disease activity (Mayo/HBI): QW and Q2W: Weeks 0, 4, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 112 |
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 |
Bosnia and Herzegovina |
Brazil |
Canada |
Colombia |
Israel |
Japan |
Korea, Republic of |
Mexico |
Montenegro |
Russian Federation |
Serbia |
South Africa |
Turkey |
Ukraine |
United States |
Belgium |
Bulgaria |
Croatia |
Czechia |
Denmark |
Estonia |
Germany |
Hungary |
Italy |
Lithuania |
Netherlands |
Poland |
Romania |
Slovakia |
Spain |
Sweden |
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
|
Subjects enrolled onto the study will be eligible to continue receiving vedolizumab SC until the vedolizumab SC formulation becomes commercially available in their country of residence, the subject withdraws from the study, or the sponsor decides to close the study. |
Si prevede che la durata del trattamento con vedolizumab SC varier¿ in base al soggetto sulla scorta del beneficio continuato, ma i soggetti arruolati nello studio saranno idonei a continuare a ricevere vedolizumab SC finch¿ la formulazione di vedolizumab SC non diventi disponibile in commercio nel proprio Paese di residenza, il soggetto non si ritiri dallo studio o lo sponsor non decida di chiudere lo studio. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |