Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA)

NCT01308255 | Completed Phase 4

• 2 other identifiers: RR05/70922005-005013-37
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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on blinded therapy and if 6 months of remission is achieved the intravenous agent (infliximab or placebo) will be withdrawn.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the change in Sharpe van der Heijde score

  50 Weeks

Secondary Outcomes (9)

• Number of patients having a major clinical response (DAS <1.6 for 6 months)

  78 Weeks

• The change in Sharpe van der Heijde scores between baseline, 26 & 72 wk hand & feet x-rays

  Week 72

• The number of patients in clinical remission (DAS <1.6) at 78 weeks

  78 Weeks

• The number of patients in infliximab free remission (DAS <1.6) at 78 weeks

  78 Weeks

• The number of patients in clinical remission (DAS <1.6) at 26 weeks

  26 Weeks

Study Arms (2)

Infliximab Arm

EXPERIMENTAL

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; Drug: Methotrexate; Dietary Supplement: Folic acid

Steroid/Placebo Arm

PLACEBO COMPARATOR

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; Drug: Methotrexate; Dietary Supplement: Folic acid

Interventions

Infliximab DRUG

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

Also known as: Remicade

Infliximab Arm

Methylprednisolone DRUG

Steroid

Also known as: Medrol, Solu-Medrol and Cadista.

Steroid/Placebo Arm

Methotrexate DRUG

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.

Also known as: Maxtrex

Infliximab Arm; Steroid/Placebo Arm

Folic acid DIETARY_SUPPLEMENT

All patients enrolled are commenced on oral folic acid 5mg daily, except the day methotrexate is taken, and the study infusions.

Also known as: vitamin B9,vitamin Bc, or folacin

Infliximab Arm; Steroid/Placebo Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Chapel Allerton Hospital

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Infliximab; Methylprednisolone; Methylprednisolone Hemisuccinate; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Paul Emery

  University of Leeds

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: March 3, 2011
• First Posted: March 4, 2011
• Study Start: September 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: November 1, 2019

Record last verified: 2019-10

Locations

GB (1)