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Etanercept and Methotrexate in Patients to Induce Remission in Early Arthritis (EMPIRE) (EMPIRE)

30 października 2019 zaktualizowane przez: Paul Emery, University of Leeds

A Multicentre Randomised Trial Of Etanercept And Methotrexate To Induce Remission In Early Inflammatory Arthritis

TRIAL DESIGN

  1. Description This is a 18-month, double-blind, randomized, multicentre, outpatient study. The approximate duration of subject participation will be 18 months and the approximate total duration of the study will be 42 months. The duration of subject enrollment will be approximately 24 months.
  2. Discussion of Trial Design The study is designed to directly compare the effectiveness of combination therapy with MTX + ETN versus
  3. Principal research question/objective To determine the number of patients in clinical remission at 12 months of follow-up, as defined as the absence of symptoms and signs of inflammatory arthritis.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

Early arthritis is frequently undifferentiated. It is well recognised that a substantial proportion of patients with an undifferentiated inflammatory arthritis will go on to develop persistent synovitis, with the strongest predictor of persistence being disease duration > 12 weeks (1-4). Studies have shown that patients with early oligoarthritis who fail to respond within 2 weeks to corticosteroid injections have a high likelihood of persistent disease (2). It is therefore clear that these patients with early inflammatory arthritis need definitive treatment, but the optimal therapeutic strategy is yet to be determined.

Tumor Necrosis Factor (TNF) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory process of rheumatoid and other arthritis, and the resulting joint pathology. Elevated levels of TNF are found in the synovial fluid of patients with RA. Two distinct receptors for TNF exist naturally as monomeric molecules on the cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNF receptors (TNFR). Etanercept (ETN) is a dimeric fusion protein consisting of the p75 TNFR linked to the Fc portion of human IgG1, and is capable of binding two TNF molecules. Etanercept inhibits binding of both TNF-alpha and TNF-beta to cell surface TNFRs, rendering TNF biologically inactive. Agents that block TNF are effective in all types of arthritis (with the exclusion of connective tissue diseases).

It is generally agreed that there is a window of opportunity in active early inflammatory arthritis in which definitive treatment may give a disproportionate improvement compared to treatment at a later time, and may well be able to induce remission in a subgroup of patients.

Studies in early rheumatoid arthritis (< 12 months) have shown that remission-induction with the TNF-antagonist infliximab provides a significant reduction in MRI-evidence of synovitis and erosions at 12 months with evidence of sustained functional and quality of life benefits at 2 years, despite withdrawal of infliximab at 12 months (5). Results from the TEMPO study show that treatment of established rheumatoid arthritis with ETN+MTX achieves remission in about 40% patients (6). TNF antagonists also have the therapeutic benefit of rapid and sustained suppression of inflammation.

Treatment of patients with early undifferentiated arthritis with ETN+MTX is hypothesised to prevent progression of persistent disabling disease in a significant number of patients. Induction of remission at this time in the disease course may result in sustained remission, reduce the need for further treatment, and be most cost effective therapeutic strategy.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

112

Faza

  • Faza 4

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Zjednoczone Królestwo
    • West Yorkshire
      • Leeds, West Yorkshire, Zjednoczone Królestwo, LS7 4SA
        • Leeds Teaching Hospital HNS Trust

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 80 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • Is age 18 -80 years old
  • Patients have articular synovitis, within 3 months of diagnosis
  • Either RF antibody (+) or anti-CCP antibody (+) or SE (+)
  • Demonstrates a negative urine pregnancy test at screening if female of childbearing potential
  • Agrees to use a medically accepted form of contraception during the study and for 3 months after the last dose of study drug, if sexually active male
  • Is capable of understanding and signing an informed consent form
  • Is able and willing to self-inject study drug or have a designee who can do so
  • Is able and willing to take oral medication
  • Is able to store injectable test article at 2° C to 8° C
  • Demonstrates a negative tuberculosis screening test

Exclusion Criteria:

  • Received previous treatment with any DMARDS
  • Received previous treatment with ETN or other tumour necrosis factor (TNF) antagonist (e.g. a TNF monoclonal antibody or a soluble TNF-receptor)
  • Previous treatment with IL-1 receptor antagonist
  • Chronic arthritis diagnosed before 16 years old
  • Received any investigational "biological" agent within 3 months of screening visit
  • Received treatment with any investigational drug of "chemical" nature within one month prior to study screening
  • Known Human Immunodeficiency Virus (HIV)
  • Presence of any contraindication to ETN or MTX
  • Has significant concurrent medical diseases
  • Has cancer or a history of cancer within 5 years of entering the screening period
  • Current crystal or infective arthritis
  • Chronic infection of the upper respiratory tract, chest, urinary tract or skin
  • Any ongoing or active infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days
  • Demonstrates liver function abnormality
  • Has renal disease
  • Has leukopenia
  • Has thrombocytopenia
  • Has a hemoglobin level of < 9g/L for males and < 85 g/L for females
  • Is pregnant or breast-feeding
  • Joint surgery within preceding 2 months (at joints to be assessed within this study)
  • Received anti-CD4, diphtheria interleukin-2 fusion protein, anti-interleukin-6 (anti-IL-6), rituximab or other immunosuppressive biologic during the last 6 months before screening, and treatment with such agents more than 6 months before screening if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening visit
  • Received any live (attenuated) vaccines within 4 weeks of screening visit
  • Received cyclophosphamide within 6 months of screening visit
  • Any corticosteroids within 28days prior to screening
  • Uses a dose of NSAID greater than the maximum recommended dose in the product information at the screening visit
  • Has a history of confirmed blood dyscrasia
  • Has any condition judged by the physician to cause this study to be detrimental to the subject
  • Has a history of drug abuse or psychiatric disease that would interfere with the ability to comply with the study protocol
  • Has a history of alcohol abuse or excessive alcohol beverage consumption
  • Has a history of known liver cirrhosis, fibrosis, or fatty liver
  • Has a history of any viral hepatitis within 1 year of screening

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Poczwórny

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Combination Therapy
Methotrexate & Etanercept
Lek: Etanercept (ETN)
ETN 50 mg subcutaneous (SC) injections once weekly and MTX orally once weekly.
Inne nazwy:
  • Enbrel
Komparator placebo: Single-agent therapy
Methotrexate (MTX)
Lek: Placebo
ETN-matching placebo SC injections once weekly and MTX orally once weekly.
Inne nazwy:
  • Maxtrex

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
clinical remission
Ramy czasowe: 12 months
To determine the number of patients in clinical remission at 12 months, as defined as the absence of symptoms and signs of inflammatory arthritis (i.e. swollen joint count 0; tender joint count 0)
12 months

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
clinical remission
Ramy czasowe: 18 months
The number of patients in clinical remission at 18 months (as defined as absence of symptoms and signs of clinical arthritis i.e. swollen joint count 0 ; tender joint count 0)
18 months
Conventional disease activity measures
Ramy czasowe: week 78
Conventional disease activity measures (VAS pain/fatigue/global/physician, EMS, TJC, SJC, CRP, ESR)
week 78
Functional, work and quality of life assessments
Ramy czasowe: Week 78
Functional, work and quality of life assessments (HAQ, WIS, WDA, EQ-5d, SF-36)
Week 78
remission
Ramy czasowe: Week 26
Proportion of patients achieving 26 weeks of remission
Week 26
DAS 44
Ramy czasowe: Week 78
Disease Activity Score (DAS) 44
Week 78
drug-free remission
Ramy czasowe: 12 & 18 mths
The number of patients in drug-free remission at 12 18 months
12 & 18 mths
etanercept-free remission
Ramy czasowe: 12 and 18 months
The number of patients in etanercept-free remission at 12 and 18 months (ETN arm)
12 and 18 months
Remission by ACR Criteria
Ramy czasowe: Week 78
Remission by ACR Criteria
Week 78
effects of the combination of ETN and MTX to MTX alone on radiographic change
Ramy czasowe: 12 months and 18 months
To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change at 12 months and 18 months
12 months and 18 months

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

University of Leeds

Śledczy

  • Główny śledczy: Paul Emery, Prof, University of Leeds

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 września 2006

Zakończenie podstawowe (Rzeczywisty)

5 listopada 2010

Ukończenie studiów (Rzeczywisty)

5 listopada 2010

Daty rejestracji na studia

Pierwszy przesłany

24 lutego 2011

Pierwszy przesłany, który spełnia kryteria kontroli jakości

24 lutego 2011

Pierwszy wysłany (Oszacować)

25 lutego 2011

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

1 listopada 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

30 października 2019

Ostatnia weryfikacja

1 października 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • RR05/7150
  • 2005-005467-29 (Numer EudraCT)

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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