E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis (RA) |
Artritis Reumatoide (AR) |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
Artritis Reumatoide (AR) |
|
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 | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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 evaluate the efficacy of nipocalimab vs placebo in participants with moderate to severe active RA. |
Evaluar la eficacia de nipocalimab frente a placebo en pacientes con Artritis Reumatoide (AR) activa de moderada a grave |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety and tolerability of nipocalimab vs placebo in participants with moderate to severe active RA. 2. To evaluate the PK and immunogenicity of IV nipocalimab in participants with moderate to severe active RA. |
1. Evaluar la seguridad y tolerabilidad de nipocalimab frente a placebo en pacientes con AR activa de moderada a grave. 2. Evaluar la farmacocinética y la inmunogenicidad de nipocalimab i.v. en pacientes con AR activa de moderada a grave. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or Female, 18 to 75 years of age (inclusive) at the time of consent. 2. Diagnosis of RA and meeting the 2010 ACR / European League Against Rheumatism (EULAR) Criteria for RA for at least 3 months before screening. 3. Has moderate to severe active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints out of the 66/68-swollen and tender joint count at the time of screening and at baseline. 4. Is positive for ACPA and/or RF at screening. 5. Screening C-reactive protein (CRP) ≥0.3 mg/dL by the central laboratory. |
1. Hombre o mujer, entre 18 y 75 años de edad (inclusive) en el momento del consentimiento. 2. Tener un diagnóstico de Artritis Reumatoide (AR) y cumplir los criterios de la ACR/Liga Europea contra el Reumatismo (EULAR) de 2010 para la AR durante al menos 3 meses antes de la selección. 3.Tener AR activa de moderada a grave, definida por la actividad persistente de la enfermedad con 6 articulaciones inflamadas y 6 dolorosas a la palpación como mínimo del recuento de 66/68 articulaciones inflamadas y dolorosas a la palpación en el momento de la selección y en la visita basal. 4. Resultado positivo para ACPA o FR en la selección. 5. Proteína C reactiva (PCR) ≥0,3 mg/dl en la selección según el laboratorio central. Por favor, refiérase a la sección 5.1 del protocolo para consultar todos los criterios de inclusión |
|
E.4 | Principal exclusion criteria |
1. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her RA or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant. 2. Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 12 weeks before the first administration of study intervention or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first administration of study intervention). 3. Is (anatomically or functionally) asplenic. 4. Has experienced myocardial infarction (MI), unstable ischemic heart disease, or stroke within 12 weeks of screening. 5. Has other known inflammatory diseases that might confound the evaluations of benefit from nipocalimab therapy, including but not limited to ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, Lyme disease. 6. Is currently taking IgG Fc-related protein therapeutics. |
1. Tener confirmación o sospecha de un síndrome de inmunodeficiencia clínico no relacionado con el tratamiento de la AR o tener antecedentes familiares de inmunodeficiencia congénita o hereditaria, a menos que se confirme su ausencia en el paciente. 2. Tener actualmente una neoplasia maligna o antecedentes de tumores malignos en los 3 años anteriores a la selección (a excepción de un carcinoma basocelular y/o carcinoma de piel de células escamosas localizado que se haya tratado adecuadamente sin signos de reaparición durante al menos 12 semanas antes de la primera administración del tratamiento del estudio o un carcinoma de cuello uterino localizado que se haya tratado sin signos de reaparición durante al menos los 3 meses anteriores a la primera administración del tratamiento del estudio). 3. Ser (anatómica o funcionalmente) asplénico. 4. Haber sufrido un infarto de miocardio (IM), una cardiopatía isquémica inestable o un accidente cerebrovascular en las 12 semanas anteriores a la selección. 5. Tener otras enfermedades inflamatorias conocidas que podrían dificultar la interpretación de las evaluaciones de los beneficios del tratamiento con nipocalimab, que incluyen, entre otras, espondilitis anquilosante, artritis psoriásica, lupus eritematoso sistémico o enfermedad de Lyme. 6. Estar tomando actualmente terapias de proteínas relacionadas con Fc de IgG Por favor, refiérase a la sección 5.2 del protocolo para consultar todos los criterios de exclusión |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline in DAS28-CRP. |
• Cambio respecto al valor basal en la DAS28-PCR |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of participants who achieve ACR20, ACR50, ACR70, and ACR90 responses. 2. Proportion of participants achieving DAS28-CRP remission. 3. Proportion of participants achieving DAS28-CRP LDA. 4. Change from baseline in HAQ-DI score. 5. Proportion of participants with treatment-emergent AE. 6. Proportion of participants with treatment-emergent SAEs. 7. Serum nipocalimab concentrations over time. 8. Incidence and titers of antibodies to nipocalimab in participants receiving active study intervention. |
1. Proporción de pacientes que logran respuestas ACR20, ACR50, ACR70 y ACR90. 2. Proporción de pacientes que logran una remisión de la DAS28-PCR. 3. Proporción de pacientes que logran una LDA en la DAS28-PCR. 4. Cambio respecto al valor basal en la puntuación del HAQ-DI. 5. Proporción de pacientes con Acontecimientos Adversos (AA) derivados del tratamiento. 6. Proporción de pacientes con Acontecimientos Adversos Graves (AAG) derivados del tratamiento. 7. Concentraciones séricas de nipocalimab a lo largo del tiempo. 8. Incidencia y valores de anticuerpos contra nipocalimab en pacientes que reciben el tratamiento activo del estudio. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 12 2. Week 12 3. Week 12 4. Week 12 5. Throughout the study 6. Throughout the study 7. W0, W2, W4, W8, W12, W18 8. W0, W2, W4, W8, W12, W18 |
1. Semana 12 2. Semana 12 3. Semana 12 4. Semana 12 5. A lo largo del estudio 6. A lo largo del estudio 7. S0, S2, S4, S8, S12, S18 8. S0, S2, S4, S8, S12, S18 |
|
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 | Yes |
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 | 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 | 2 |
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 | 14 |
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 |
United States |
Germany |
Poland |
Spain |
United Kingdom |
|
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 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 19 |