E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus (SLE) |
Lupus Eritemetoso Sistemico (SLE) |
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E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus (SLE) |
Lupus Eritemetoso Sistemico (SLE) |
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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 | 16.1 |
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 |
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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 |
Primary:
1. Evaluate the efficacy of atacicept compared to placebo in reducing SLE disease activity in subjects treated with standard of care (SoC) therapy and to investigate the dose-response relationship.
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Obiettivo principale:
1. Valutare l'efficacia di atacicept rispetto a placebo nel ridurre l'attività della malattia LES nei soggetti sottoposti a terapia standard (TS) ed esaminare il rapporto dose-risposta. |
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E.2.2 | Secondary objectives of the trial |
Secondary:
1. Evaluate the effect of atacicept in reducing corticosteroid (CS) usage.
2. Evaluation of changes in disease activity over time.
3. Evaluate the safety, tolerability and immunogenicity profile of atacicept.
4. Evaluate the pharmacokinetics (PK) and pharmacodynamic (PD) profiles of atacicept.
5. Evaluate the effect of atacicept on patient-reported outcomes (PROs).
Other:
1. Identify potential associations of genetic variations with drug response, efficacy and safety.
2. Identify potential associations of gene expression profiles before and after atacicept treatment with drug response, efficacy and safety.
3. Identify potential associations of the profiles of circulating proteins before and after atacicept treatment with drug response, efficacy and safety.
4. Evaluate the effect of atacicept in reducing damage accrual from SLE (Systemic Lupus International Collaborating Clinics [SLICC]/American College of Rheumatology [ACR] damage index). |
- Valutare l’effetto di atacicept nel ridurre l'utilizzo di corticosteroidi (CS);
- Valutare l'effetto di atacicept sulle variazioni dell'attività della malattia nel tempo;
- Valutare i profili di sicurezza, tollerabilità e immunogenicità di atacicept nei soggetti affetti da LES;
- Valutare il profilo farmacocinetico (PK) e farmacodinamico (PD) di atacicept nei soggetti affetti da LES;
- Valutare l'effetto di atacicept sugli esiti riferiti dai pazienti;
Altro:
- Identificare eventuali associazioni tra variazioni genetiche ed espressione genica e risposta, efficacia e sicurezza di atacicept.
- Identificare eventuali associazioni tra i profili di espressione genica prima e dopo il trattamento con atacicept con risposta, efficacia e sicurezza di atacicept.
- Valutare l'effetto di atacicept nel ridurre l'impatto dei danni derivanti da LES (in base al Systemic Lupus International Collaborating Clinics [SLICC]/American College of Rheumatology [ACR] Damage Index)
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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 |
Pharmacokinetic study; Objective see E.2.2 |
Studio di farmacocinetica
Obiettivi: vedere E 2.2
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E.3 | Principal inclusion criteria |
- Male or female of ≥18 years of age, who provide written informed consent at the screening visit
- SLEDAI-2K score ≥6 at screening visit
- Diagnosis of SLE satisfying at least 4 out of the 11 ACR classification criteria for SLE during the course of their illness at the screening visit
- Disease duration of at least 6 months from the time of diagnosis (when the subject met at least 4 of the ACR criteria) at the screening visit
- Positive test results for ANA (human epithelial cell [Hep]-2 ANA = or >1:80) and/or anti-dsDNA antibody (≥30 IU/mL) at screening visit
- Other protocol defined inclusion criteria may apply |
- I soggetti maschi e femmine idonei maggiorenni che firmano il consenso informato alla visita di screening;
- Indice SLEDAI-2K ≥6 alla visita di screening;
- Diagnosi SLE cbe soddisfi almeno 4 degli 11 criteri ACR per LES durante la visita di screening;
- Durata della malattia di almeno 6 mesi dal momento della diagnosi (da quando il soggetto ha soddifsatto almeno 4 criteri ACR) alla visita di screening;
- Risultato positivo al test degli anticorpi antinucleo (ANA) (human epithelial cell [Hep]-2 ANA = o > 1:80) e/o agli anticorpi anti-acido deossiribonucleico a doppia elica (anti-dsDNA) (≥30 IU/mL) alla visita di screening;
- Possono essere applicati altri criteri di inclusione come definito dal protocollo
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E.4 | Principal exclusion criteria |
- History or current diagnosis of any demyelinating disease
- Active central nervous system SLE deemed to be severe or progressive
- Use of cyclophosphamide within 3 months before or during SV
- Active, moderate to severe glomerulonephritis and/or severe renal impairment (spot urine protein:creatinine ratio [UPCr] ≥2 mg/mg
-Other protocol defined exclusion criteria may apply |
- Non possono partecipare i soggetti affetti da malattia demielinizzante;
- LES severo del sistema nervoso centrale, considerata grave o progressiva;
- soggetti che hanno utilizzato ciclofosfamide entro 3 mesi dalla visita di screening o durante la visita di screening;
- Glomerulonefrite attiva, da moderata a grave e/o grave insufficienza renale [rapporto proteine-creatinina nelle urine (UPCr) ≥2 mg/mg/die];
- Possono essere applicati altri criteri di esclusione come definito dal protocollo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with SRI response at Week 24 compared to the screening visit |
La percentuale di soggetti con risposta alla Settimana 24 rispetto alla visita di screening. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Proportion of subjects at Week 24 whose prednisone-equivalent CS dose has been reduced from screening visit (SV) by ≥25% and to a dose of ≤7.5mg/day, and have no BILAG A or 2B flare in disease activity during Weeks 16 through 24
- Proportion of subjects in the patient global impression of change (PGIC) categories at Week 24
- Change from screening visit to Week 24 in prednisone-equivalent CS daily dose
- Time to first SRI response during treatment period
- Proportion of subjects responding to treatment according to the BILAG-based Combined Lupus Assessment (BICLA), at week 24
- Change from Day 1 in SF-36 PCS, MCS and total score at each time point
- Nature, incidence, severity, and outcome of AEs |
- Percentuale di soggetti che alla Settimana 24 hanno avuto una riduzione ≥25% della dose di CS prednisone-equivalente dalla visita di screening, fino ad arrivare a una dose ≤7,5 mg/die e che non hanno mostrato nessun BILAG A o flare 2B nell'attività della malattia dalla Settimana 16 alla 24;
- Percentuale di soggetti nelle categorie 1 o 2, 3 o 4 o 5, 6 o 7 del Patient Global Impression of Change (PGIC) alla Settimana 24;
- Cambiamento della dose giornaliera di CS prednisone-equivalente dalla visita di screening alla Settimana 24;
- Tasso di risposta SRI durante il priodo di trattamento;
- Percentuale di soggetti responsivi al trattamento secondo il BICLA (BILAG-based Combined Lupus Assessment), alla settimana 24;
- Variazione dal Giorno 1 nell'SF-36 PCS (Medical Outcomes Study 36-item Short Form Health Survey (SF-36) Physical Component Summary), nel Mental Component Summary (MCS) e nel punteggio totale a ogni punto temporale.
- Natura, incidenza, la gravità, e l'esito di eventi avversi
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker and Health resource utilization |
Biomarker e utilizzo dei servizi di cura |
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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 | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Bulgaria |
Italy |
Argentina |
Brazil |
Chile |
Czech Republic |
Germany |
Korea, Republic of |
Spain |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
South Africa |
Ukraine |
United Kingdom |
United States |
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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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When final database lock occurs (according to protocol) |
quando verrà effettuato il database lock, in accordo al protocollo |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |