Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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

7. juli 2022 opdateret af: 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.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

812

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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).

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Active conventional therapy (ACT)
Non-biological DMARD's: Methotrexate plus steroids or Methotrexate plus Sulphasalazine and Hydroxychloroquine and steroids
Medicin: 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)
Aktiv komparator: Biologic agent 1
Cimzia: Certolizumab-pegol plus Methotrexate and steroids
Biologisk: Cimzia
Certolizumab-pegol: 200 mg s.c. hver anden uge. Methotrexat: 25mg/uge
Aktiv komparator: Biologic agent 2
Orencia: Abatacept plus Methotrexate and steroids
Biologisk: Orencia
Abatacept: 125 mg s.c. hver uge. Methotrexat: 25mg/uge
Aktiv komparator: Biologic agent 3
RoActemra: Tocilizumab plus Methotrexate and steroids
Biologisk: 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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
The proportion of patients in remission at week 24 from baseline according to CDAI
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Karolinska Institutet

Efterforskere

  • Ledende efterforsker: Ronald van Vollenhoven, MD, Prof., The Karolinska Institute

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

14. december 2012

Primær færdiggørelse (Forventet)

1. juli 2023

Studieafslutning (Forventet)

1. december 2023

Datoer for studieregistrering

Først indsendt

8. december 2011

Først indsendt, der opfyldte QC-kriterier

12. december 2011

Først opslået (Skøn)

14. december 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

8. juli 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

7. juli 2022

Sidst verificeret

1. juli 2022

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NORD-STAR
  • 2011-004720-35 (EudraCT nummer)
  • 2011/2069-31/4 (Anden identifikator: Regional Ethical Review Board)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Studiedata/dokumenter

  1. Studieprotokol
    Oplysningskommentarer: Publication of the protocol. Glinatsi et al. Trials (2017) 18:161

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Rheumatoid arthritis

Kliniske forsøg med Cimzia

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Singapore

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner