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Active Conventional Therapy Compared to Three Different Biologic Treatments in Early Rheumatoid Arthritis With Subsequent Dose Reduction

7 de julio de 2022 actualizado por: Ronald van Vollenhoven, prof., Karolinska Institutet

A Multicenter, Randomized, Open-label, Blinded-assessor, Phase 4 Study in Patients With Early Rheumatoid Arthritis to Compare Active Conventional Therapy Versus Three Biologic Treatments, and Two De-escalation Strategies in Patients Who Respond to Treatment

This is an international (Sweden, Finland, Norway, Denmark, Iceland and the Netherlands) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare

  1. the proportion of subjects who achieve remission with ACT versus three different biologic therapies (Certolizumab-pegol, Abatacept or Tocilizumab)
  2. two alternative de-escalation strategies in patients who respond to first-line therapy.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

After completed enrollment a total of 812 patients were included in the study.

371 of the included patients have entered treatment part 2, 256 patients have exited the study after treatment part 1, 207 patients have had early termination and 322 patients have completed the full study.

Tipo de estudio

Intervencionista

Inscripción (Actual)

812

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Dinamarca
      • Aalborg, Dinamarca
        • Aalborg University Hospital
      • Aarhus, Dinamarca
        • Aarhus University Hospital
      • Copenhagen, Dinamarca
        • Rigshospitalet
      • Odense, Dinamarca
        • Odense University Hospital
      • Silkeborg, Dinamarca
        • Silkeborg University Clinic
      • Svendborg, Dinamarca
        • Svendborg Hospital OUH
      • Sønderborg, Dinamarca
        • University Hospital of Southern Denmark
  • Finlandia
      • Helsinki, Finlandia
        • Helsinki University Central Hospital
      • Jyväskylä, Finlandia
        • Central Finland Central Hospital
      • Kuopio, Finlandia
        • Kuopio University Hospital
      • Tampere, Finlandia
        • Tampere University Hospital
  • Islandia
      • Reykjavík, Islandia
        • Landspitali University Hospital
  • Noruega
      • Bergen, Noruega
        • Haukeland University Hospital
      • Oslo, Noruega
        • Diakonhjemmet Hospital
      • Tromsø, Noruega
        • University Hospital of North Norway
      • Trondheim, Noruega
        • St. Olav's Hospital
      • Ålesund, Noruega
        • Ålesund Hospital
  • Países Bajos
      • Amsterdam, Países Bajos
        • Reade
  • Suecia
      • Falun, Suecia
        • Falu Hospital
      • Gothenburg, Suecia
        • Sahlgrenska University Hospital
      • Huddinge, Suecia
        • The Karolinska University Hospital
      • Linköping, Suecia
        • Linköping University Hospital
      • Lund, Suecia
        • Skåne University Hospital
      • Malmö, Suecia
        • Skåne University Hospital
      • Solna, Suecia
        • The Karolinska University Hospital
      • Stockholm, Suecia
        • Academic Specialist Center
      • Stockholm, Suecia
        • The Karolinska Institutet
      • Uppsala, Suecia
        • Uppsala University Hospital
      • Västerås, Suecia
        • Västmanlands Hospital
      • Örebro, Suecia
        • Örebro University Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Subject is ≥18 years of age.
  2. Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria, 2010. (Patients should also be classified according to the 1987-revised ACR-classification criteria, without this being an inclusion criteria).
  3. <24 months from arthritis symptom debut (symptom duration will be registered).
  4. Subject must have DAS28 (CRP) > 3.2.
  5. ≥ 2 swollen joints AND ≥ 2 tender joints.
  6. Subject must fulfill one of the following three criteria: RF positive OR ACPA positive OR CRP >10 mg/L.

  7. Female subject is either not of childbearing potential (postmenopausal, surgically sterile etc.), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion:

    • Intrauterine device (IUD)
    • Contraceptives (oral, parenteral, patch) for three months prior to study drug administration)
    • A vasectomized partner
  8. Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit.
  9. Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening.
  10. Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
  11. Subjects must be able and willing to self-administer s.c. injections or have a qualified person available to administer s.c. injections.

Exclusion Criteria:

  1. Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases.
  2. Current active inflammatory joint disease other than RA.
  3. Subjects has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.
  4. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed.
  5. Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).
  6. Subject has chronic arthritis diagnosed before age 17 years.
  7. Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs.
  8. Subject has been treated with any investigational drug within one month prior to screening visit.
  9. Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks of screening.
  10. Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.
  11. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).
  12. Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.

  13. Subject has history of cancer or lymphoproliferative disease. Allowable exceptions:

    1. Successfully treated cutaneous squamous cell or basal cell carcinoma
    2. Localized carcinoma in situ of the cervix
    3. Curatively treated malignancy (treatment terminated) > 5 years prior to screening
  14. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the BL visit.
  15. Subjects will be evaluated for latent TB infection with a PPD or QuantiFERON test and X-ray. Subjects with evidence for latent TB will not be enrolled but first assessed according to local guidelines.
  16. Subject is known to have immune deficiency, history of Human Immunodeficiency Virus (HIV) or is otherwise severely immunocompromised.
  17. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication.
  18. Men who are planning to father a child during the time they are included in the study
  19. Subject has a history of clinically significant drug or alcohol usage in the last year.
  20. Subject has a chronic widespread pain syndrome.
  21. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
  22. Subject is unwilling to comply with the study protocol.

  23. Screening clinical laboratory analyses show any of the following abnormal laboratory results:

    1. Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.75 times upper limit of normal (ULN).
    2. Positive serum human chorionic gonadotropin (hCG).
    3. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology indicative of current infection.
    4. Creatinine levels > 2x the ULN. If creatinine 1-2 times ULN, check GFR.
    5. Hemoglobin < 90 g/L.
    6. Absolute neutrophil count (ANC) < 1.5 x 10^3/microL.
    7. Serum total bilirubin > 1.5 mg/dL (>26 micromol/L).

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Único

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Active conventional therapy (ACT)
Non-biological DMARD's: Methotrexate plus steroids or Methotrexate plus Sulphasalazine and Hydroxychloroquine and steroids
Droga: Non-biological DMARD's
Methotrexate: 25mg/week. SSZ: 2 g/day. HCQ: 35 mg/kg/week (Finland and Denmark) Methotrexate: 25mg/week. Prednisolone 20 mg/day tapered in 9 weeks to 5 mg/day, discontinued after 9 months. (Sweden, Norway, Iceland, and the Netherlands)
Comparador activo: Biologic agent 1
Cimzia: Certolizumab-pegol plus Methotrexate and steroids
Biológico: Cimzia
Certolizumab-pegol: 200 mg s.c. cualquier otra semana. Metotrexato: 25mg/semana
Comparador activo: Biologic agent 2
Orencia: Abatacept plus Methotrexate and steroids
Biológico: Orencia
Abatacept: 125 mg s.c. cada semana. Metotrexato: 25mg/semana
Comparador activo: Biologic agent 3
RoActemra: Tocilizumab plus Methotrexate and steroids
Biológico: RoActemra

Tocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week.

Methotrexate: 25mg/week

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
The proportion of patients in remission at week 24 from baseline according to CDAI
Periodo de tiempo: 24 weeks from BL
Treatment Part 1: The primary efficacy outcome is the proportion of patients in remission at week 24 from BL according to CDAI
24 weeks from BL
The proportion of patients in remission at week 24 after dose-reduction according to CDAI
Periodo de tiempo: 24 weeks after dose-reduction
Treatment Part 2: The primary efficacy outcome is the proportion of patients in remission according to CDAI, at the time point 24 weeks after the dose was first reduced
24 weeks after dose-reduction
The radiographic progression of total Sharp van der Heijde score after 48 weeks from baseline
Periodo de tiempo: 48 weeks from BL
The primary efficacy outcome is the progression of total Sharp van der Heijde score after 48 weeks from BL
48 weeks from BL

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Karolinska Institutet

Investigadores

  • Investigador principal: Ronald van Vollenhoven, MD, Prof., The Karolinska Institute

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

14 de diciembre de 2012

Finalización primaria (Anticipado)

1 de julio de 2023

Finalización del estudio (Anticipado)

1 de diciembre de 2023

Fechas de registro del estudio

Enviado por primera vez

8 de diciembre de 2011

Primero enviado que cumplió con los criterios de control de calidad

12 de diciembre de 2011

Publicado por primera vez (Estimar)

14 de diciembre de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de julio de 2022

Última actualización enviada que cumplió con los criterios de control de calidad

7 de julio de 2022

Última verificación

1 de julio de 2022

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • NORD-STAR
  • 2011-004720-35 (Número EudraCT)
  • 2011/2069-31/4 (Otro identificador: Regional Ethical Review Board)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Datos del estudio/Documentos

  1. Protocolo de estudio
    Comentarios de información: Publication of the protocol. Glinatsi et al. Trials (2017) 18:161

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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