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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by University of Leeds.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Leeds
ClinicalTrials.gov Identifier:
NCT01303874
First received: February 24, 2011
Last updated: NA
Last verified: February 2011
History: No changes posted
  Purpose

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.

Condition Intervention Phase
Rheumatoid Arthritis
Arthritis
Drug: Etanercept (ETN)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre Randomised Trial Of Etanercept And Methotrexate To Induce Remission In Early Inflammatory Arthritis

Resource links provided by NLM:


Further study details as provided by University of Leeds:

Primary Outcome Measures:
  • clinical remission [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • clinical remission [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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)

  • Conventional disease activity measures [ Time Frame: week 78 ] [ Designated as safety issue: No ]
    Conventional disease activity measures (VAS pain/fatigue/global/physician, EMS, TJC, SJC, CRP, ESR)

  • Functional, work and quality of life assessments [ Time Frame: Week 78 ] [ Designated as safety issue: No ]
    Functional, work and quality of life assessments (HAQ, WIS, WDA, EQ-5d, SF-36)

  • remission [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Proportion of patients achieving 26 weeks of remission

  • DAS 44 [ Time Frame: Week 78 ] [ Designated as safety issue: No ]
    Disease Activity Score (DAS) 44

  • drug-free remission [ Time Frame: 12 & 18 mths ] [ Designated as safety issue: No ]
    The number of patients in drug-free remission at 12 18 months

  • etanercept-free remission [ Time Frame: 12 and 18 months ] [ Designated as safety issue: No ]
    The number of patients in etanercept-free remission at 12 and 18 months (ETN arm)

  • Remission by ACR Criteria [ Time Frame: Week 78 ] [ Designated as safety issue: No ]
    Remission by ACR Criteria

  • effects of the combination of ETN and MTX to MTX alone on radiographic change [ Time Frame: 12 months and 18 months ] [ Designated as safety issue: No ]
    To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change at 12 months and 18 months


Enrollment: 112
Study Start Date: September 2006
Estimated Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Therapy
Methotrexate & Etanercept
Drug: Etanercept (ETN)
ETN 50 mg subcutaneous (SC) injections once weekly and MTX orally once weekly.
Other Name: Enbrel
Placebo Comparator: Single-agent therapy
Methotrexate (MTX)
Drug: Placebo
ETN-matching placebo SC injections once weekly and MTX orally once weekly.
Other Name: Maxtrex

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01303874

Locations
United Kingdom
Leeds Teaching Hospital HNS Trust
Leeds, West Yorkshire, United Kingdom, LS7 4SA
Sponsors and Collaborators
University of Leeds
Investigators
Principal Investigator: Paul Emery, Prof University of Leeds
  More Information

No publications provided

Responsible Party: Professor Emery; Chief Investigator, University of Leeds
ClinicalTrials.gov Identifier: NCT01303874     History of Changes
Other Study ID Numbers: RR05/7150, 2005-005467-29
Study First Received: February 24, 2011
Last Updated: February 24, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Leeds:
Rheumatoid arthritis
Inflammatory arthritis
Undifferentiated arthritis
Etanercept
Combination Therapy

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
TNFR-Fc fusion protein
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on April 16, 2014