E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Artritis Reumatoide |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Artritis Reumatoide |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 |
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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 |
To evaluate the change in disease activity following intravenous (i.v.) administration of two doses of NNC0114-0006 compared to placebo in subjects with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy |
Evaluar la variación de la actividad de la enfermedad tras la administración intravenosa (IV) de dos dosis de NNC0114 0006 en comparación con placebo en sujetos con artritis reumatoide (AR) tratados con metotrexato (MTX) de fondo. |
|
E.2.2 | Secondary objectives of the trial |
- To describe the safety and tolerability of NNC0114-0006 - To describe the immunogenicity of NNC0114-0006 - To describe the pharmacokinetics (PK) of NNC0114-0006 - To compare the pharmacodynamic (PD) effects of NNC0114-0006 and placebo on various biomarkers, including markers on disease activity and structural damage - To compare effects of NNC0114-0006 and placebo on patient reported outcomes (PROs) |
-Describir la seguridad y la tolerabilidad de NNC0114 0006. -Describir la inmunogenicidad de NNC0114 0006. -Describir la farmacocinética (FC) de NNC0114 0006. -Comparar los efectos farmacodinámicos (FD) de NNC0114 0006 y placebo sobre varios biomarcadores, entre ellos, marcadores de la actividad de la enfermedad y del daño estructural. -Comparar los efectos de NNC0114 0006 y placebo sobre resultados comunicados por los pacientes (RCP). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- A diagnosis of RA meeting the 2010 ACR classification criteria, obtained at least 6 months prior to dosing with the trial product (If the diagnosis was made prior to 2010 a diagnosis meeting the 1987 ACR classification criteria is acceptable) - Active RA characterised by DAS28-CRP ? 4.5 and at least five tender and five swollen joints (can be the same joints) of the 28 joint count - Concomitant treatment with MTX ? 15 mg/week for at least 4 months prior to screening, with stable dose of ? 15 mg/week and ? 25 mg/week for at least 6 weeks prior to screening (MTX doses between 7.5 and 12.5 mg/week are allowed, if patient had intolerance to 15 mg/week) - Biologic naïve subjects or subjects having been treated with biologics for RA (biologic experienced) provided they meet one of the following criteria: a. Reason for discontinuation of biologic therapy was intolerance (e.g., unable to receive recommended doses or achieve adequate treatment duration because of drug related side effects) b. Discontinued biologic therapy for other reasons than lack of efficacy (primary or secondary failure) or intolerance (e.g., drug holiday) - Females and males with age between 18 and 75 years (both included) |
-Diagnóstico de AR que cumpla los criterios de clasificación del ACR de 2010, efectuado al menos 6 meses antes de la administración del producto del ensayo (en caso de que el diagnóstico se haya hecho antes de 2010, será aceptable un diagnóstico que cumpla los criterios de clasificación del ACR de 1987). -AR activa caracterizada por una puntuación DAS28-PCR ? 4,5 y por la presencia de al menos cinco articulaciones dolorosas y cinco articulaciones inflamadas (pueden ser las mismas) a partir del recuento de 28 articulaciones. -Tratamiento concomitante con MTX ? 15 mg/semana durante al menos 4 meses antes de la selección, con una dosis estable ? 15 y ? 25 mg/semana durante al menos 6 semanas antes de la selección (se permitirán dosis de MTX de entre 7,5 y 12,5 mg/semana cuando el paciente haya presentado intolerancia a 15 mg/semana). -Sujetos sin tratamiento previo con productos biológicos o que hayan recibido tratamiento con productos biológicos para la AR (experiencia con biológicos) siempre que cumplan uno de los criterios siguientes: a.El motivo de la suspensión del tratamiento biológico fue intolerancia (por ejemplo, imposibilidad de recibir las dosis recomendadas o de alcanzar la duración adecuada del tratamiento debido a efectos secundarios relacionados con el fármaco). b.Suspensión del tratamiento biológico por motivos distintos de falta de eficacia (fracaso primario o secundario) o intolerancia (por ejemplo, ?vacaciones farmacológicas?). -Mujeres y varones con una edad comprendida entre 18 y 75 años (ambos incluidos). |
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E.4 | Principal exclusion criteria |
- Body mass index (BMI) ?18.0 or ?38.0 kg/m2 - Subjects with rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty?s syndrome). Subjects with secondary Sjögren?s syndrome or stable hypothyroidism are eligible. - Any active or ongoing bacterial infections within 4 weeks prior to randomisation, unless treated and resolved with appropriate therapy (e.g., simple urinary tract infection) - Any history of recurrent infections or conditions predisposing to chronic infections (e.g., brochiectasis, chronic osteomyelitis) - History of severe systemic fungal infection within the past 12 months prior to screening unless treated and resolved with appropriate therapy |
-Índice de masa corporal (IMC) ? 18,0 o ? 38,0 kg/m2. -Sujetos con enfermedad autoinmunitaria reumática distinta de la AR, o afectación sistémica importante secundaria a AR (entre otras, vasculitis, fibrosis pulmonar o síndrome de Felty). Podrán participar sujetos con síndrome de Sjögren secundario o hipotiroidismo estable. -Cualquier infección bacteriana activa o en curso en las 4 semanas previas a la aleatorización, a menos que se haya tratado y resuelto con el tratamiento adecuado (por ejemplo, infección urinaria simple). -Antecedentes de infecciones recurrentes o de enfermedades que predispongan a infecciones crónicas (por ejemplo, bronquiectasias u osteomielitis crónica). -Antecedentes de micosis sistémica grave en los 12 meses previos a la selección a menos que se haya tratado y resuelto con el tratamiento adecuado. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in disease activity score based on 28 joints and c-reactive protein (DAS28-CRP) |
Cambio en la actividad de la enfermedad basada en 28 articulaciones y proteína C reactiva (DAS28-PCR) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Week 12 |
Desde la visita basal a semana 12 |
|
E.5.2 | Secondary end point(s) |
1- ACR20/50/70 2- Incidence of adverse events (AEs) 3- Incidence of antibodies against NNC0114-0006 4- Terminal serum half-life (t½) 5- Change in serum levels of total IL-21 6- Change in Health Assessment Questionnaire ? Disability Index score (HAQ-DI) |
1-ACR20/50/70 en la semana 12. 2-Incidencia de acontecimientos adversos (AA) 3-Incidencia de anticuerpos contra NNC0114 4-Semivida sérica terminal (t½) 5-Variación de la concentración sérica de IL-21 6-Variación de la puntuación HAQ-DI (Cuestionario de evaluación de la salud ? Índice de discapacidad) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- At Week 12 2- Up to Week 24 3- Up to Week 24 4- After second dose administration at Week 6 5- Up to Week 12 6- From baseline to Week 12 |
1- En la semana 12 2- Hasta la semana 24 3- Hasta la semana 24 4- Despues de la administración de la segunda dosis en la semana 6 5- Hasta la semana 12 6- Desde la visita basal hasta la semana 12 |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, immunogenicity |
Tolerabilidad, inmunogenicidad |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Hungary |
Latvia |
Poland |
Russian Federation |
Serbia |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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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LVLS |
Último paciente, última visita |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 16 |