Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) (IDEA)

October 30, 2019 updated by: Paul Emery, University of Leeds

A Multi-centre Randomised Double Blind Placebo Controlled Study Comparing Two Regimens of Combination Therapy in Early DMARD Naive Rheumatoid Arthritis.

This is a placebo controlled randomised clinical trial.Patients attending Yorkshire Early Arthritis Clinics and diagnosed with rheumatoid arthritis with symptom duration of 3-12 months will be recruited. They will be randomised to blinded therapy with either methotrexate and intravenous corticosteroid at baseline, or methotrexate and intravenous infliximab according to the standard treatment regime. Patients will be followed regularly, and at each visit, if the patients are not in remission, they will be given an intramuscular injection of corticosteroid. After 26 weeks, all patients will be unblinded and those with an inadequate treatment response will be treated according to a dose escalation algorithm until they achieve remission. Those in remission will continue on blinded therapy and if 6 months of remission is achieved the intravenous agent (infliximab or placebo) will be withdrawn.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The main aim of the study is to compare the efficacy of biologic therapy (infliximab) as induction therapy against current best practice therapy: early introduction of methotrexate in combination with steroid induction therapy and dose modification according to predefined disease activity measures (as informed by the literature, and based around a pragmatic dose escalation protocol).

Exploratory analyses of imaging findings will be undertaken on a subgroup of patients at sites able to perform such assessments.

The imaging techniques used include

  1. DEXA
  2. US
  3. Peripheral MRI

End point

The end points of the study are defined as:

  • Completion of 78 weeks of therapy in the study
  • Withdrawal due to any reason including toxicity or inefficacy
  • Withdrawal due to completion of the dose escalation regime and disease remains active
  • Withdrawal due to meeting NICE criteria for biologics during the dose escalation regime

At the end of the study, patients will continue to be followed in the Yorkshire Rheumatology clinics as part of their routine care.

All patients who withdraw will be asked to have a withdrawal visit with X-Rays of hands and feet to allow assessment of the primary endpoint.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
112

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS7 4SA
        • Chapel Allerton Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men & Women 18-80 years of age.
  • Fulfil 1987 ACR criteria for RA.
  • Symptoms of > 3 months and < 12 months duration.
  • Men and women must use adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion or dose of methotrexate.
  • The patient must be able to adhere to the study visit schedule and other protocol requirements.
  • The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
  • Must have a chest radiograph within 3 months prior to first treatment dose with no evidence of malignancy, infection or fibrosis.
  • Are considered eligible according to the tuberculosis (TB) eligibility assessment.
  • Active disease as defined by DAS > 2.4.
  • TNF therapy naïve.
  • DMARD therapy naïve.
  • Negative hepatitis B and C screening tests within 3 months prior to screening.

Exclusion Criteria:

  • Women who are pregnant, nursing, or men or women planning pregnancy within 24 months after screening.
  • Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
  • Previous or current treatment with any other therapeutic agent targeted at reducing TNF.
  • Prior treatment with any DMARD.
  • Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months.
  • Documented HIV infection.
  • Hepatitis- B or Hepatitis-C serology positive (must be checked within 3 months prior to screening).
  • Are considered ineligible according to the TB eligibility assessment.
  • Have or have had an opportunistic infection within 6 months prior to screening.
  • Significant haematological or biochemical abnormality.
  • Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
  • Concomitant congestive heart failure, including medically controlled asymptomatic patients.
  • Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening).
  • Malignancy within the past 5 years.
  • History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease.
  • Known recent substance abuse (drug or alcohol).
  • Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
  • Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB.
  • Have a positive Mantoux test or evidence of active TB infection, or recent close contact with an individual with active TB.
  • Previous oral, IM, IA or IV corticosteroids within 1 month prior to baseline.
  • Receiving treatment with anakinra.
  • Contra-indications to methotrexate, infliximab or steroids.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Infliximab Arm
For those randomised to the infliximab arm, infliximab will be administered at a dose of 3mg/kg according to the standard treatment protocol.
Drug: Infliximab

Prior to week 26

  • Infliximab 3mg/kg standard regime (weeks 0, 2, 6, 14, 22)
  • Methotrexate commencing at 10mg weekly, progressing to 20mg by week 6.
  • Folic acid 5 mg daily except the day methotrexate is taken

Patients will be unblinded at week 26 and then treated pragmatically guided by disease activity

Other Names:
  • Remicade
Drug: Methotrexate
All patients enrolled are commenced on oral methotrexate 10mg once a week The methotrexate dose should be increased to 15 mg at the week 2 visit. The methotrexate should be increased to 20mg at the week 6 visit.
Other Names:
  • Maxtrex
Dietary supplement: Folic acid
All patients enrolled are commenced on oral folic acid 5mg daily, except the day methotrexate is taken, and the study infusions.
Other Names:
  • vitamin B9,vitamin Bc, or folacin
Placebo Comparator: Steroid/Placebo Arm
Patients randomised to this arm will receive an IV infusion of 250mg methylprednisolone at week 0 & those without an adequate clinical response after 26 wks will receive additional steroid as IM methylprednisolone 120mg. Patients on this arm will receive an IV placebo infusion of 250ml of 9mg/l NaCl.
Drug: Methylprednisolone
Steroid
Other Names:
  • Medrol, Solu-Medrol and Cadista.
Drug: Methotrexate
All patients enrolled are commenced on oral methotrexate 10mg once a week The methotrexate dose should be increased to 15 mg at the week 2 visit. The methotrexate should be increased to 20mg at the week 6 visit.
Other Names:
  • Maxtrex
Dietary supplement: Folic acid
All patients enrolled are commenced on oral folic acid 5mg daily, except the day methotrexate is taken, and the study infusions.
Other Names:
  • vitamin B9,vitamin Bc, or folacin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The primary endpoint is the change in Sharpe van der Heijde score
Time Frame: 50 Weeks
50 Weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Number of patients having a major clinical response (DAS <1.6 for 6 months)
Time Frame: 78 Weeks
78 Weeks
The change in Sharpe van der Heijde scores between baseline, 26 & 72 wk hand & feet x-rays
Time Frame: Week 72
Week 72
The number of patients in clinical remission (DAS <1.6) at 78 weeks
Time Frame: 78 Weeks
78 Weeks
The number of patients in infliximab free remission (DAS <1.6) at 78 weeks
Time Frame: 78 Weeks
78 Weeks
The number of patients in clinical remission (DAS <1.6) at 26 weeks
Time Frame: 26 Weeks
26 Weeks
RA Quality of Life questionnaire
Time Frame: 78 Weeks
78 Weeks
Health Assessment Questionnaire
Time Frame: 78 Weeks
78 Weeks
Immunogenetic studies to predict long-term immune response
Time Frame: 78 Weeks
78 Weeks
Immune phenotyping (flow cytometry) and assessment of immune effector & regulatory functions
Time Frame: 78 Weeks
78 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Leeds

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Paul Emery, University of Leeds

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 3, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RR05/7092
  • 2005-005013-37 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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