E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | IgG4-related disease | Enfermedad relacionada con la IgG4 | |
E.1.1.1 | Medical condition in easily understood language | Immunoglobulin G4 related disease | Enfermedad relacionada con la inmunoglobulina G4 | |
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 | 10077271 | E.1.2 | Term | Immunoglobulin G4 related disease | E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders | |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | To evaluate the safety and the ability of daily oral administration of rilzabrutinib to maintain glucocorticoid-free remission in participants with IgG4-RD for at least 24 weeks | Evaluar la seguridad y la capacidad de la administración oral diaria de rilzabrutinib para mantener la remisión libre de glucocorticoides en participantes con IgG4-RD durante al menos 24 semanas | |
E.2.2 | Secondary objectives of the trial | - To evaluate the effect of rilzabrutinib on IgG4-RD disease activity over time - To evaluate the effect of rilzabrutinib on specific protein biomarkers over time | - Evaluar el efecto de rilzabrutinib sobre la actividad de la enfermedad IgG4-RD a lo largo del tiempo - Evaluar el efecto de rilzabrutinib en biomarcadores proteicos específicos a lo largo del tiempo | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | - Be male or female with age ≥18 years. - Have a clinical diagnosis of IgG4-RD. - Be willing to taper off an equivalent prednisone dose of between 20-40 mg/day in 2 weeks. | - Ser hombre o mujer con edad ≥18 años. - Tener un diagnóstico clínico de IgG4-RD. - Estar dispuesto a disminuir una dosis equivalente de prednisona entre 20-40 mg/día en 2 semanas | |
E.4 | Principal exclusion criteria | - Currently or within 6 months of screening taking rituximab, other B-cell depleting agents, or alkylating agents unless B cell concentrations have been demonstrated by flow cytometry to return to normal values (defined as 5 cells per cubic mm). - History of solid organ transplant - Positive at Screening for HIV, hepatitis B, hepatitis C, or TB - Female patients who are pregnant or nursing. | - Actualmente o dentro de los 6 meses posteriores a la selección tomando rituximab, otros agentes que reducen las células B o agentes alquilantes, a menos que se haya demostrado que las concentraciones de células B vuelven a los valores normales (definidas como 5 células por mm cúbico) mediante citometría de flujo. - Historial de trasplante de órgano sólido - Positivo en la prueba de detección de VIH, hepatitis B, hepatitis C o TB - Mujeres que están embarazadas o amamantando. | |
E.5 End points |
E.5.1 | Primary end point(s) | 1. Proportion of participants who are without disease flare for at least 24 consecutive weeks following the first dose of rilzabrutinib. Disease flare is defined as an increase from screening IgG4-RD responder index (RI) >2 or initiation of rescue treatment. 2. Incidence of SAE, AE leading to discontinuation and possible glucocorticoid-related AE. 3. Number of participants with Potentially clinically significant abnormalities (PCSAs) for clinical laboratory tests, vital signs and ECG | 1. Proporción de participantes sin brotes de la enfermedad durante al menos 24 semanas consecutivas tras la primera dosis de rilzabrutinib. El brote de la enfermedad se define como un aumento del índice de respuesta (IR) de IgG4-RD de detección > 2 o el inicio del tratamiento de rescate. 2. Incidencia de SAE, AE que lleva a la interrupción y posible AE relacionado con glucocorticoides. 3. Número de participantes con anomalías potenciales clínicamente significativas (PCSA) para pruebas clínicas de laboratorio, signos vitales y ECG | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | 1. At Week 52 2, 3. Up to 68 weeks | 1. En la semana 52 2, 3. Hasta 68 semanas | |
E.5.2 | Secondary end point(s) | 1. Proportion of participants with reduction from baseline IgG4-RD RI activity score ≥2 points at Week 12 2. Proportion of patients with an IgG4-RD RI activity score = 0 at Week 12 3. Level and change from baseline of each subclass of the serological markers 4. Proportion of participants achieving reduction in baseline serum IgG4 level of 10% at 12 weeks 5. Change from baseline in IgG4-RD RI over time 6. Proportion of participants with no disease flares between Week 4 and Week 12, and between Week 12 and Week 52 (or the end of the treatment extension period) among the participants who have treatment extension 7. Change from baseline over time in IgG4-RD damage, as recorded on the damage portion of the IgG4-RD RI | 1.Proporción de participantes con una reducción en la puntuación de la actividad del IR de la ER-IgG4 ≥2 puntos en la semana 12 con respecto al momento inicial. 2. Proporción de participantes con una puntuación de la actividad del IR de la ER-IgG4 igual a 0 en la semana 12. 3. Nivel y cambio desde el inicio de cada subclase de los marcadores serológicos 4. Proporción de participantes que logren una reducción en el nivel inicial de IgG4 en suero del 10 % a las 12 semanas. 5. Cambio con respecto al momento inicial en el IR de la ER-IgG4 a lo largo del tiempo. 6. Proporción de participantes sin reagudizaciones de la enfermedad entre las semanas 4 y 12, y entre las semanas 12 y 52 (o el final del periodo de tratamiento de mantenimiento) en los participantes que tengan una prolongación del tratamiento. 7. Cambio con respecto al momento inicial en el daño de la ER-IgG4, registrado en la parte de daño del IR de la ER-IgG4, a lo largo del tiempo. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | 1, 2, 3. At Week 52 4. At Week 12 5, 7. From baseline to Week 52 6. Until Week 52 | 1, 2, 3. En la semana 52 4. En la semana 12 5, 7. Desde el inicio hasta la semana 52 6. Hasta la semana 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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Canada | United States | France | Spain | Italy | |
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 | LVLS | La última visita del último paciente | |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 27 |