E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Systemic Lupus Erythematosus |
Lupus Eritematoso Sistemico attivo |
|
E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus |
Lupus Eritematoso Sistemico |
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025139 |
E.1.2 | Term | Lupus erythematosus systemic |
E.1.2 | System Organ Class | 100000004859 |
|
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 |
Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the SRI-4 response |
Valutare l’efficacia di efavaleukin alfa alla settimana 52 in base alla risposta SRI-4 |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the efficacy of efavaleukin alfa at week 52, as measured by the BICLA index responses - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by LLDAS response - Evaluate the efficacy of efavaleukin alfa at week 52, as measured by OCS tapering - Evaluate the efficacy of efavaleukin alfa at week 24, as measured by SRI-4 response - Evaluate the efficacy of efavaleukin alfa at week 24, as measured by the BICLA index responses - Evaluate the efficacy of efavaleukin alfa at weeks 24 and 52, as measured by hSLEDAI - Evaluate the efficacy of efavaleukin alfa on joints and skin - Evaluate the efficacy of efavaleukin alfa using BILAG score - Evaluate the efficacy of efavaleukin alfa using patient reported outcomes - Characterize the safety of efavaleukin alfa - Characterize the PK of efavaleukin alfa |
- Valutare l’efficacia di efavaleukin alfa alla settimana 52 in base alle risposte dell’indice BICLA - Valutare l’efficacia di efavaleukin alfa alla settimana 52 in base alla risposta LLDAS - Valutare l’efficacia di efavaleukin alfa alla settimana 52 in base alla riduzione graduale degli OCS - Valutare l’efficacia di efavaleukin alfa alla settimana 24 in base alla risposta SRI-4 - Valutare l’efficacia di efavaleukin alfa alla settimana 24 in base alle risposte dell’indice BICLA - Valutare l’efficacia di efavaleukin alfa alle settimane 24 e 52 in base allo strumento hSLEDAI - Valutare l’efficacia di efavaleukin alfa sulle articolazioni e la cute - Valutare l’efficacia di efavaleukin alfa utilizzando il punteggio BILAG - Valutare l’efficacia di efavaleukin alfa utilizzando gli esiti riferiti dai pazienti - Caratterizzare la sicurezza di efavaleukin alfa - Caratterizzare la PK di efavaleukin alfa |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject has provided informed consent prior to initiation of any study specific activities/procedures - Age >= 18 years to 75 years at screening - Fulfills classification criteria for SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE (Aringer et al, 2019), with antinuclear antibody >= 1:80 by immunofluorescence on Hep-2 cells being present at screening. AntidsDNA results based on the Phadia method will be used for SLE classification criteria and for the purposes of hSLEDAI scoring during screening and throughout the study - Hybrid SLEDAI score >= 6 points with a "Clinical" hSLEDAI score >= 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine and immunologic parameters. Including the following protocol specific rules: - Arthritis: for hSLEDAI scoring purposes, arthritis must involve small joints in the hands or wrists. - Alopecia: subjects should have hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia >= 2. - Oral ulcers: ulcers location and appearance must be documented by the investigator. - Scleritis and episcleritis: the presence of stable SLE-related scleritis and episcleritis (ie, that will likely not require initiation/increase in immunosuppressants/immunomodulators as outlined in the inclusion/exclusion criteria) must be documented by an ophthalmologist and other causes excluded. - Renal: subjects with urine protein/creatinine ratio < 3000 mg/g (or equivalent) in a clean catch spot urine sample can enroll and be scored in the hSLEDAI, provided the subject has a clinical hSLEDAI >= 4. - Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI
*Please refer to protocol for the full list |
- I soggetti hanno fornito il consenso informato prima di iniziare qualsiasi attività/procedura studio specifica - Età >=18 anni fino a 75 anni al momento dello screening - Soddisfare i criteri di classificazione del LES in accordo ai criteri di classificazione per il LES del 2019 dell'European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) con anticorpi antinucleo >=1:80 rilevati tramite immunofluorescenza su cellule Hep-2 allo screening. I risultati di AntidsDNA basati sul metodo Phadia vengono utilizzati per i criteri di classificazione del LES e ai fini del punteggio hSLEDAI durante lo screening e durante lo studio - Punteggio hSLEDAI >=6 punti con un punteggio hSLEDAI clinico >=4 punti. Il punteggio hSLEDAI "clinico" corrisponde alla valutazione del punteggio hSLEDAI senza l'inclusione di punti attribuibili ai risultati di laboratorio, inclusa l'urina e parametri immunologici. Comprese le seguenti regole protocollo specifiche: - Artrite: ai fini del punteggio hSLEDAI, l'artrite deve coinvolgere articolazioni piccole delle mani o dei polsi. - Alopecia: i soggetti devono presentare caduta dei capelli senza cicatrici; non devono presentare né alopecia areata né alopecia androgenetica; e dovrebbero avere un punteggio di attività CLASI per l'alopecia >= 2. - Ulcere orali: la posizione e l'aspetto delle ulcere devono essere documentate dall'investigatore. - Sclerite e episclerite: la presenza di sclerite ed episclerite stabile correlata al LES (cioè, che probabilmente non richiederanno inizio/aumento di immunosoppressori/immunomodulatori come delineati nei criteri di inclusione/esclusione) devono essere documentati da un oftalmologo e devono essere escluse altre cause. Renale: i soggetti con rapporto proteina dell'urina/creatinina <3000mg/g (o equivalente) in un campione pulito di urina possono essere arruolati e valutati nel hSLEDAI, e il soggetto ha un hSLEDAI clinico >= 4. - Pleurite e pericardite: sintomi di pleurite e pericardite devono essere accompagnati da riscontri oggettivi per essere valutati nel hSLEDAI.
*Fare riferimento al protocollo per la lista completa |
|
E.4 | Principal exclusion criteria |
- Lupus nephritis with urine protein creatinine ratio > 3000 mg/g at screening or having required induction therapy within 1 year prior to screening. - Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis. Other Medical Conditions: - Currently present or within 1 year prior to screening a diagnosis of any inflammatory joint or skin disease other than SLE which would interfere with SLE disease assessment based on investigator judgement. - History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 4 months prior to screening. - Active infection for which anti-infectives were indicated within 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening visit. - Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.
*Please refer to the protocol for the full list |
- Nefrite da lupus con rapporto di creatinina proteica urinaria> 3000 mg / g allo screening o che ha richiesto una terapia di induzione entro 1 anno prima dello screening. - Lupus attivo del SNC entro 1 anno prima dello screening inclusi, ma non limitati a, meningite asettica, atassia, vasculite del SNC, neuropatia cranica, sindrome demielinizzante, neurite ottica, psicosi, convulsioni o mielite trasversa. Altre condizioni mediche: - Diagnosi attualmente presente o entro 1 anno prima dello screening di qualsiasi malattia infiammatoria articolare o della pelle diversa dal LES che interferirebbe con la valutazione della malattia LES sulla base del giudizio dello sperimentatore. - Storia di qualsiasi malattia diversa dal LES che abbia richiesto un trattamento con corticosteroidi orali o parenterali per> 2 settimane entro 4 mesi prima dello screening. - Infezione attiva per la quale gli antinfettivi sono stati indicati entro 4 settimane prima della visita di screening OPPURE presenza di infezione grave, definita come la necessità di ricovero in ospedale o di antinfettivi per via endovenosa entro 8 settimane prima della visita di screening. - Tubercolosi attiva o tubercolosi latente senza anamnesi passata documentata di trattamento adeguato secondo lo standard di cura locale.
*Fare riferimento al protocollo per la lista completa |
|
E.5 End points |
E.5.1 | Primary end point(s) |
SRI-4 response at week 52 |
Risposta SRI-4 alla settimana 52 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- BICLA response at week 52 - LLDAS response at week 52 - Reduction of OCS to <= 7.5 mg/day by week 44 and sustained through week 52 in subjects with a baseline OCS dose = 10 mg/day - SRI-4 response at week 24 - BICLA response at week 24 - hSLEDAI response (ie, reduction >= 4 points from baseline) at week 24 - hSLEDAI response (ie, reduction = 4 points from baseline) at week 52
*Please refer to protocol for the full list |
- Risposta BICLA alla settimana 52 - Risposta LLDAS alla settimana 52 - Riduzione di OCS a <=7,5 mg/die entro la settimana 44 e mantenuta fino alla settimana 52 in soggetti con una dose al basale di OCS >=10 mg/die - Risposta SRI-4 alla settimana 24 - Risposta BICLA alla settimana 24 - Risposta hSLEDAI (ossia, riduzione >= 4 punti rispetto al basale) alla settimana 24 - Risposta hSLEDAI (ossia, riduzione >= 4 punti rispetto al basale) alla settimana 52
*Fare riferimento al protocollo per la lista completa |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 8, 12, 24, 36, and 52; Settimane 8, 12, 24, 36 e 52 |
|
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 | No |
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) | 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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Canada |
Chile |
Colombia |
Hong Kong |
Japan |
Mexico |
Russian Federation |
Taiwan |
Turkey |
United States |
Austria |
Bulgaria |
France |
Italy |
Poland |
Switzerland |
Greece |
|
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
|
Completion of follow-up |
Al completamento del follow-up |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |