E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythmatosus |
Lupus Sistemico Eritematoso |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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 |
The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with moderate to severe general SLE despite standard of care treatments (ie, corticosteroids, and potentially antimalarials and immunosuppressants) continued from Baseline. |
L’obiettivo primario dello studio e' confermare l’efficacia clinica di epratuzumab nel trattamento di soggetti affetti da LES generale da moderato a grave nonostante le terapie standard ricevute (ovvero corticosteroidi e, potenzialmente, antimalarici e immunosoppressori) senza interruzione dal basale. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the safety, tolerability, and immunogenicity of epratuzumab, and to assess the steroid-sparing effects of epratuzumab treatment. |
Gli obiettivi secondari dello studio consistono nella valutazione della sicurezza, tollerabilita' e immunogenicita' di epratuzumab e nella valutazione degli effetti del trattamento con epratuzumab nella riduzione dell’uso di steroidi |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
OTHER SUBSTUDIES: The sub-study is included in this protocol as exploratory objective:
exploratory analyses of genomic, genetic, and proteomic biomarkers
may also be performed.
|
ALTRI SOTTOSTUDI: Il sottostudio e' incluso nel protocollo SL0010 con obiettivi esplorativi: potranno inoltre essere effettuate analisi esplorative di genomica, genetica e proteomica (biomarkers).
|
|
E.3 | Principal inclusion criteria |
- Positive antinuclear antibodies (ANA) at Screening (Visit 1) - Current clinical diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria such that at least 4 of the 11 criteria are met - Active moderate to severe SLE activity as demonstrated by the British Isles Lupus Assessment Group Index (BILAG) - Active moderate to severe SLE disease as demonstrated by SLEDAI total score. - On stable SLE treatment regimen, including mandatory corticosteroids and immunosuppressants or antimalarials |
- Il soggetto ha risultati positivi ai test degli anticorpi anti nucleo (ANA) o anti-dsDNA allo Screening (Visita 1); - Il soggetto ha una diagnosi di LES (Lupus Eritematoso Sistemico) formulata da un medico sulla base dei piu' recenti criteri ACR modificati con conferma di almeno 4 criteri su 11; - Il soggetto e' affetto da LES in forma attiva da moderato a grave, come documentato da un punteggio BILAG; - Il soggetto e' affetto da LES in forma attiva da moderato a grave, come evidenziato da un punteggio totale SLEDAI; - I soggetti devono essere in terapia SLE con una dose stabile, inclusi corticosteroidi, immunosoppressori o antimalarici obbligatori. |
|
E.4 | Principal exclusion criteria |
- Subjects who are breastfeeding, pregnant, or plan to become pregnant - Subjects with active, severe SLE disease activity which involves the renal system - Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A disease. - Subjects with the evidence of an immunosuppressive state - Subjects who, in the opinion of the investigator, are at a particularly high risk of significant infection - History of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma. - Subjects receiving any live vaccination within the 8 weeks prior to screening (Visit 1). - Subjects with history of infections, including but not limited to concurrent acute or chronic viral hepatitis B or C - Subjects with substance abuse or dependence or other relevant concurrent medical condition - Subjects with history of thromboembolic events within 1 year of screening Visit. - Subjects with significant hematologic abnormalities - Subject has received treatment with other anti- B cell antibodies within 12 months prior to screening (visit 1) - Subject use of oral anticoagulant (not including) nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 weeks prior to screening (Visit 1) - Subject has previously participated in this study or has previously received epratuzumab treatment. |
- I soggetti di sesso femminile in allattamento, gravidanza o che pianifichino una gravidanza; - Il soggetto e' affetto da LES in forma attiva di grado grave a carico del sistema renale; - Il soggetto e' affetto da LES neuropsichiatrico in forma attiva di grado grave, definito da un punteggio BILAG di grado A per qualsiasi patologia neuropsichiatrica; - Evidenze di immunosoppressione nei soggetti; - I soggetti che, secondo l’opinione dello sperimentatore, sono esposti a un rischio particolarmente elevato di infezioni significative; - Storia di neoplasia maligna, a eccezione delle seguenti forme trattate: carcinoma in situ della cervice, carcinoma basocellulare o carcinoma squamocellulare cutaneo; - I soggetti che hanno ricevuto qualsiasi vaccino vivo (anche attenuato) nelle 8 settimane precedenti lo Screening (Visita 1); - I soggetti con una storia di infezioni croniche, inclusi a titolo puramente esemplificativo i soggetti affetti da epatite B o C virale concomitante in forma cronica o acuta; - I soggetti in condizione di abuso/dipendenza da sostanze o affetti da altre patologie mediche concomitanti; - Il soggetto ha una storia di eventi tromboembolici nell’anno precedente lo Screening (Visita 1); - Anomalie significative ematologiche; - Il soggetto ha ricevuto una precedente terapia con altri anticorpi anti-cellule B nei 12 mesi precedenti lo Screening; - Uso di anticoagulanti orali (esclusi i FANS) nelle 12 settimane precedenti lo Screening (Visita 1); - Il soggetto ha partecipato in precedenza a questo studio o ha assunto in precedenza epratuzumab. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The percent of subjects meeting treatment response criteria at Week 48 according to a combined response index |
La percentuale di soggetti responder alla Settimana 48 in base a un indice di risposta combinata |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
a) The percent of subjects meeting treatment response criteria at Week
24, according to the combined index.
b) The percent of subjects meeting treatment response criteria at Week
12, according to the combined index.
c) The percent of subjects meeting treatment response criteria at Week
36, according to the combined index.
d) Change from Baseline in daily corticosteroid dose at Week 24
e) Change from Baseline in daily corticosteroid dose at Week 48 |
a) la percentuale di soggetti responder alla Settimana 24 in base a un indice di risposta combinata. b) la percentuale di soggetti responder alla Settimana 12 in base a un indice di
risposta combinata. c) la percentuale di soggetti responder alla Settimana 36 in base a un indice di risposta combinata. d) modifica dal baseline nella dose giornaliera di corticosteroidi alla Settimana 24. e) modifica dal baseline nella dose giornaliera di corticosteroidi alla Settimana 48. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) 24 weeks
b) 12 weeks
c) 36 weeks
d) Baseline - 24 weeks |
a) 24 settimane b) 12 settimane c) 36 settimane d) Baseline - 24 Settimane e) Baseline - 48 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 | Yes |
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 | 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 | 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 | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Brazil |
Canada |
India |
Mexico |
Russian Federation |
South Africa |
Ukraine |
|
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 end of study is defined as the date of the last visit of the last subject in the study |
Conclusione sperimentazione: LVLS, ultima visita ultimo soggetto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 29 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 29 |
E.8.9.2 | In all countries concerned by the trial days | 0 |