E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sjogren's syndrome. |
Sindrome di Sjogren primaria. |
|
E.1.1.1 | Medical condition in easily understood language |
Sjogren's syndrome. |
Sindrome di Sjogren. |
|
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue 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 demonstrate a dose response of VAY736 defined as change in multidimensional disease activity as assessed by the physician from baseline at 24 weeks. |
Dimostrare la relazione dose- risposta di VAY736 definita come variazione nell’indice ESSDAI (EULAR Sjögren’s Syndrome Disease Activity Index) dal basale a 24 settimane. |
|
E.2.2 | Secondary objectives of the trial |
- To assess a dose response of VAY736 in the change from baseline of ESSPRI at 24 weeks - To assess a dose response of VAY736 in the change from baseline of the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) at 24 weeks - To assess changes from baseline in PhGA of the patient’s overall disease activity at week 24 - To assess a dose response of VAY736 in the change from baseline of SF-36 at 24 weeks - To evaluate the effects of VAY736 on salivary gland function at 24 weeks - To evaluate CD19+ B-cell counts before and after VAY736 treatment, and time to recovery. For further secondary objectives please refer to the protocol. |
- Valutare la relazione dose - risposta di VAY736 nella variazione rispetto al basale di ESSPRI a 24 settimane. - Valutare la relazione dose - risposta di VAY736 nella variazione rispetto alla basale della scala FACITF (Functional Assessment of Chronic Illness Therapy-Fatigue) a 24 settimane. - Valutare le variazioni rispetto al basale nella valutazione complessiva da parte del medico (Physician’s Global Assessment – PhGA) dell’attività di malattia globale del paziente alla settimana 24. - Valutare la relazione dose- risposta di VAY736 nella variazione rispetto al basale nel questionario SF-36 a 24 settimane. - Valutare gli effetti di VAY736 sulla funzione delle ghiandole salivari a 24 settimane. - Valutare le conte delle cellule B CD19+ prima e dopo il trattamento con VAY736, e il tempo al recupero. Per ulteriori obiettivi secondari si prega di far riferimento al protocollo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients aged 18 to 75 years - Fulfilled revised American European Consensus Group criteria for pSS - ESSDAI value =6 at baseline, based on weighted scores of the 7 domains: biologic, hematologic, articular, cutaneous, glandular, lymphadenopathy and constitutional - ESSPRI value =5 at baseline - Seropositive at screening for anti-Ro/SSA antibodies - Stimulated whole salivary flow rate at screening of >0.1 mL/min |
- Pazienti di sesso maschile e femminile di età compresa tra 18 e 75 anni - Soddisfacimento dei criteri revisionati dell’American European Consensus Group (AECG) per la pSS - Valore ESSDAI = 6 al basale, in base ai punteggi pesati dei 7 domini: biologico, ematologico, articolare, cutaneo, ghiandolare, linfadenopatia e costituzionale - Valore ESSPRI (EULAR Sjögren’s Syndrome Patient Reported Index) = 5 al basale - Sieropositività per anticorpi anti-Ro/SSA allo screening - Tasso di flusso salivare intero stimolato >0.1 mL/min allo screening |
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E.4 | Principal exclusion criteria |
- Secondary Sjögren’s syndrome (presence of another connective tissue disease) - Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations - Prior use of any B-cell depleting therapy (e.g., rituximab or other anti- CD20 mAb, anti-CD22 mAb or anti-CD52 mAb) a. within 1 year prior to randomization b. or as long as B-cell count <50 cells/µL - Current use of prednisone >10 mg/day [or equivalent other corticosteroid] or dose change within 2 weeks prior to randomization - Prior treatment with any of the following within 180 days prior to randomization (anti-BAFF mAb; CTLA4-Fc Ig (abatacept); anti-TNF-a mAb; intravenous/subcutaneous immunoglobulin (Ig); plasmapheresis; i.v. or oral cyclophosphamide; oral cyclosporine - Active viral, bacterial or other infections requiring systemic treatment at the time of screening or enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms - Receipt of live/attenuated vaccine within a 2 month period before baseline - Positive hepatitis B, hepatitis C, HIV or tuberculosis test results at screening |
- Sindrome di Sjögren’s secondaria (presenza di un’altra patologia del tessuto connettivo) - Utilizzo di altri farmaci sperimentali entro 5 emivite dall’arruolamento o entro 30 giorni a seconda di quale dei due periodi sia più lungo, o più a lungo se richiesto dalle normative locali - Uso pregresso di terapia di deplezione delle cellule B (ad es. rituximab o altro mAb anti-CD20, mAb anti-CD22 o mAb anti-CD52) a. o entro 1 anno prima della randomizzazione b. o fino a che la conta delle cellule B <50 cellule/µL - Attuale uso di prednisone > 10 mg/die [o altro corticosteroide equivalente] o variazione della dose nelle 2 settimane precedenti la randomizzazione - Pregresso trattamento con uno qualsiasi dei seguenti entro 180 giorni prima della randomizzazione: mAb anti-BAFF; Ig CTLA4-Fc (abatacept); mAb anti-TNF-a; immunoglobuline (Ig) per via endovenosa/sottocutanea; plasmaferesi; ciclofosfamide per via endovenosa od orale; ciclosporine per via orale - Infezione attiva virale, batterica o altre infezioni che necessitano di un trattamento sistemico al momento dello screening o dell’arruolamento, o anamnesi di infezione clinicamente significativa ricorrente o di infezioni batteriche con organismi incapsulati - Vaccinazione con vaccini vivi/attenuati nei 2 mesi precedenti il basale - Risultati postivi ai test per epatite B, epatite C, HIV o tubercolosi allo screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Dose-response measured by change in multi-dimensional disease activity as assessed by the physician. |
Relazione dose-risposta misurata dalla variazione dell'attività multidimensionale della malattia valutata dal medico. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 24 weeks |
Oltre 24 settimane |
|
E.5.2 | Secondary end point(s) |
- Dose-response measured by change in patient-reported disease activity measures - Change in quality of life measured by PROs - Change in salivary gland function measured by flow rate - Pharmacokinetics of VAY736 over time - Assessment of AEs, SAEs, Immunogenicity
Other protocol defined endpoints may apply. |
- Relazione dose-risposta misurata dalla variazione delle misure di attività della malattia riportate dal paziente - Variazione della qualità della vita misurata dai professionisti - Variazione della funzione delle ghiandole salivari misurata dalla portata - Farmacocinetica di VAY736 nel tempo - Valutazione di eventi avversi, eventi avversi, immunogenicità
Possono essere applicati altri endpoint definiti dal protocollo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Over 24 weeks
|
Oltre 24 settimane |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 |
immunogenicity |
immunogenicità |
|
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Chile |
Israel |
Japan |
Russian Federation |
Taiwan |
United States |
Austria |
Belgium |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Romania |
Spain |
United Kingdom |
Argentina |
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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
|
The study will complete when the last subject completes their Study Completion visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator. |
Lo studio sarà completo quando l’ultimo soggetto (LVLS) completerà l’ultima visita, e tutti gli esami previsti in questa ultima visita. |
|
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 | 3 |
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 |