E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sjögren’s Syndrome (SjS) |
Síndrome de Sjögren (SS). |
|
E.1.1.1 | Medical condition in easily understood language |
Sjögren’s Syndrome (SjS) |
Síndrome de Sjögren (SS). |
|
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 | 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 characterize the dose-response relationship of LOU064 based on change from baseline in ESSDAI at Week 24 |
El objetivo principal es caracterizar la relación dosis-respuesta de LOU064 según el cambio respecto a la basal en el ESSDAI en la semana 24. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate: - the efficacy of LOU064 compared to placebo with respect to change from baseline on patient- and physician-reported outcomes over time. - the dose-response profile of LOU064 based on change in ESSPRI at Week 24. - the efficacy of LOU064 compared to placebo with respect to change from baseline in ESSDAI over time. - the safety and tolerability of LOU064.
To assess PK parameters of LOU064. |
Objetivo 1: evaluar el perfil dosis-respuesta de LOU064 según el cambio respecto a la basal en ESSPRI en la semana 24. Objetivo 2: evaluar la eficacia de LOU064 comparado con placebo enrelación con el cambio respecto a la basal del paciente y los criterios de valoración por el médico (ESSPRI, FACIT-F, EQ-5D, EGM) a lo largo del tiempo. Objetivo 3: evaluar la eficacia de LOU064 comparado con placebo en relación con el cambio respecto a la basal en el ESSDAI a lo largo del tiempo. Objetivo 4: evaluar la seguridad y tolerabilidad de LOU064 mediante la notificación de AA que hayan aparecido con el tratamiento (graves y no graves), constantes vitales anómalas y valores de ECG y de laboratorio durante el estudio. Objetivo 5: evaluar los parámetros PK de LOU064 (Cmax, AUC, Tmax, MRT y otros en caso necesario) en estado de equilibrio. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained before any study assessment is performed. 2. Male or female patients aged 18 to 75 years at screening. 3. Classification of Sjögren's Syndrome according to the 2016 ACR/EULAR criteria at screening. 4. Screening ESSDAI (based on weighted score) ≥ 5 from 8 defined domains (biologic, hematologic, articular, cutaneous, glandular, lymphadenopathy, renal, constitutional). Patients with involvement of one or more of the remaining 4 domains are eligible but scores of these domains will not contribute to the assessment for eligibility, but will be part of the overall ESSDAI score for that subject. 5. Screening ESSPRI ≥ 5. 6. Seropositive for anti-Ro/SSA antibodies at or within 3 months prior to screening 7. Unstimulated whole salivary flow rate of > 0 mL/min at screening |
-La firma del consentimiento informado debe ser obtenida previa a cualquier procedimiento del estudio. -Pacientes de ambos sexos entre 18 y 75 años de edad en la selección. -Clasificación del síndrome de Sjögren según los criterios de 2016 ACR/EULAR en la selección. -ESSDAI en la selección (según la puntuación ponderada) >/=5 de 8 dominios definidos (biológico, hematológico, articular, cutáneo, glandular, linfadenopatía, renal, constitucional). Los pacientes con afectación de uno o más dominios de los 4 restantes son elegibles; la puntuación de estos dominios no contribuirá a la evaluación de elegibilidad, pero será parte de la puntuación global del ESSDAI de ese sujeto. -ESSPRI en la selección >/=5. -Seropositivo para los anticuerpos anti-Ro/SSA a los 3 meses o durante los 3 meses anteriores a la selección. -Tasa de flujo salival no estimulado >0 ml/min en la selección. |
|
E.4 | Principal exclusion criteria |
1. Sjögren's Syndrome overlap syndromes where another autoimmune disease constitutes the primary illness. 2. Rituximab or other B cell depleting drug within 12 months of Screening. For subjects who received such drug, their B cell count should be within normal range. 3. Prior treatment with any of the following within 6 months of baseline: • CTLA4-Fc Ig (abatacept) • Anti-TNF-α mAb • Intravenous Ig • Plasmapheresis • i.v. or oral cyclophosphamide • i.v. or oral cyclosporine A 4. Required regular use of medications known to cause, as a major side effect, dry mouth / eyes, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study. 5. Significant bleeding risk or coagulation disorders, including but not limited to: • History or presence of thrombotic or thromboembolic event, or increased risk for thrombotic or thromboembolic event • Requirement for anti-platelet or anticoagulant medication (for example, warfarin, or clopidogrel or Novel Oral Anti-Coagulant - NOAC) other than acetylsalicylic acid (up to 100 mg/d) • History of gastrointestinal or intracerebral or otherwise severe prior bleeding events, including in association with use of Nonsteroidal Anti-Inflammatory Drug (NSAID) 6. Screening CBC laboratory values as follows: • Hemoglobin levels below 10 g/dL • Total leukocyte count less than 3,000/µL • Platelets less than 100,000/µL • Neutrophil count ≤ 1,500/ µL |
Síndromes de superposición del síndrome de Sjögren en los que otra enfermedad autoinmune constituye la enfermedad principal. -Rituximab u otro fármaco que provoque la depleción de células B durante los 12 meses de la selección. Para los sujetos que reciban este fármaco, su recuento de células B debe permanecer en un rango normal. -Tratamiento previo con cualquiera de los fármacos siguientes durante los 6 meses anteriores a la basal: ·CTLA4-Fc de Ig (abatacept); ·AM anti-TNF-α; ·lg intravenosa; ·plasmaféresis; ·ciclofosfamida i.v o por vía oral; ·ciclosporina A i.v o por vía oral. -Uso regular requerido de medicamentos que causan, como efecto secundario principal, boca/ojos secos, y que no han estado en una dosis estable durante al menos los 30 días anteriores a la selección o cualquier cambio previsto en la pauta del tratamiento durante el curso del estudio. -Riesgo de hemorragia considerable o trastornos de coagulación, que incluyen entre otros: ·Antecedentes o presencia de un acontecimiento trombótico o tromboembólico, o presentar un mayor riesgo de ellos. ·Uso requerido de medicación antiplaquetaria o anticoagulante (por ejemplo, warfarina, clopidogrel o nuevos anticoagulantes orales [NACO]), salvo ácido acetilsalicílico (hasta 100 mg/d). ·Antecedentes de acontecimientos gastrointestinales o intracerebrales, o acontecimientos hemorrágicos previos graves, incluidos los asociados al uso de fármacos antinflamatorios no esteroideos (AINE). -Valores de laboratorio de CBC en la selección como: ·niveles de hemoglobina inferiores a 10 g/dl; ·recuento total de leucocitos inferior a 3000/µl; ·nivel de plaquetas inferior a 100 000/µl; ·recuento de neutrófilos </=1500/µl. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in ESSDAI at Week 24 |
Cambios en el ESSPRI desde la visita basal hasta la semana 24 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in ESSPRI, FACIT-F, EQ-5D and PhGA over time. - Change from baseline in ESSPRI at Week 24. - Change from baseline in ESSDAI over time. - PK parameters AUC, Cmax, Tmax and MRT and others as needed.
- Safety endpoints will include but not be limited to: - Occurrence of treatment emergent adverse events (both serious and non-serious) during the study. - Occurrence of treatment emergent abnormal vital signs, laboratory and ECG during the study. |
Cambios en el ESSPRI, FACIT-F, EQ-5D y PhGA desde la visita Basal hasta el final del ensayo. Cambios en el ESSPRI desde la visita basal hasta la semana 24. Cambios en el ESSDAI desde la visita basal hasta el final del ensayo. Parametros de PKs, AUC, Cmax y MRT y otros que se necesiten.
Los objetivos de seguridad incluirán, entre otros, los siguientes: Aparición de efectos adversos emergentes del tratamiento (graves y no graves) durante el estudio. Aparición de valores anormales emergentes de los signos vitales, parámetros de laboratorio laboratorio y ECG durante el ensayo. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 |
Quality of Life |
Calidad de vida |
|
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 | 7 |
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 | 40 |
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 |
Australia |
Belgium |
Bulgaria |
China |
Denmark |
Germany |
Hungary |
Poland |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
Jordan |
|
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
|
Study completion is defined as the date when the last subject finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision. |
La finalización del estudio se define como la fecha en que el último paciente finaliza la visita de fin del estudio y cualquier evaluación repetida asociada con esta visita ha sido documentada y monitorizada de manera adecuada por el investigador o, en el caso de una decisión de finalización anticipada del estudio, la fecha de esa decisión |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |