Adult subjects with a diagnosis of Rheumatoid Arthritis presenting with a disease flare after an initial response to infliximab MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Sponsors
Schering-Plough Research Institute, a division of Schering Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The subject must meet ALL of the criteria listed below for entry into the study: 1. Subject must demonstrate their willingness to participate in the study and comply with it s procedures by signing a written informed consent form. 2. Subject aged 18 years or more of either sex and any race, with RA according to ACR criteria (see appendix 3). 3. Subject has RA according to ACR criteria (see appendix 3). 4. Subject received the standard Remicade® dosing schedule as per the EU label: 3mg/kg (as per current clinical practice, rounding off [so as to empty the whole vial] will be allowed in this protocol (Appendix 5 should be used as a guide, but local procedures for rounding should be followed, and the exact dose given should be recorded in the patient’s charts and in the eCRF) at approximately weeks 0, 2, 6, (and 14) in combination with methotrexate. 5) Initial response documented by moderate or good DAS28 improvement (EULAR criteria) from week 0 to week 6 or 14 during the initial Remicade® induction period. 6) Early disease flare as defined by the “inverse” EULAR criteria (see Appendix 4) and reflects (a) a DAS28 worsening of at least 0.6 between the time of initial response (i.e. at week 6 or 14 during the induction period; see above) and the next 8-weekly infusion (i.e. week 14 or 22 of the induction period, respectively) and (b) the resulting DAS28 value. 7) Subjects must confirm that they are practicing adequate contraception: (1) Female subjects of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active during the study) must agree to use a medically accepted method of contraception or be surgically sterilized prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male and female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, oral or injectable hormonal contraceptive, and surgical sterilization (e.g. hysterectomy or tubal ligation). 8) Female subjects of childbearing potential must have a negative pregnancy test at Screening. 9) Subject must understand and be able to adhere to the dosing and visit schedules, and agree to record weekly disease activity VAS scores accurately and consistently in a weekly diary. 10) Subjects must be eligible for anti-TNF treatment according to applicable local guidelines. For all patients chest X-ray and PPD skin test results must be available at baseline. 11) Subjects screening laboratory tests must meet the following criteria: • Hemoglobin 8.0 mg/dL or greater providing the low hemoglobin level is not due to diseases other than anemia of chronic inflammation. • WBC equal to or greater than 3,500 / mm3 • Neutrophils equal to or greater than 1,500 / mm3 • Platelets equal to or greater than 100,000 / mm3 • Liver enzyme levels less than or equal to 3 times the upper limit of normal • Serum creatinine less than or equal to 1.5 mg/dL Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The subject will be excluded from entry into the study if ANY of the criteria listed below are met. 1) Subject is a female who is pregnant, intends to become pregnant during the study (or within 6 months after study completion), is nursing or not using adequate contraceptive measures. 2) Subject has not observed the designated periods for any of the concomitant medications outlined in Section 7.2. 3) Subject has used any investigational medical product within 30 days prior to Baseline. 4) Subject has any clinically significant deviation from normal in the physical examination or chest X-ray that, in the investigator’s judgment, may interfere with the study evaluation or affect subject safety. 5) Subject has rheumatic disease other than RA or has any systemic inflammatory condition with signs and symptoms that might confound the evaluations of safety and toxicity from the infliximab therapy, including, but not limited to, active Lyme disease, systemic lupus erythematous, infectious or reactive arthritis, Reiter’s syndrome, non-rheumatoid vasculitis, or parvovirus infection. 6) Subject is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study. 7) Subject is participating in any other interventional study(ies). 8) Subject is part of the staff or a family member of the staff personnel directly involved with this study. 9) Subject has an allergic reaction to or has a sensitivity to the study drug or its excipients that requires corticosteroid pre-infusion medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether, in patients presenting with a disease flare after an initial good or moderate response to infliximab, increasing either the infusion dose or infusion frequency results in a significant improvement in disease activity. ;Secondary Objective: To compare the impact on disease activity of increasing the infusion dose to increasing the infusion frequency. To compare whether the timing of the disease flare has an impact on the effect seen after the increase of does or frequency. To compare the change in disease activity during the infusion interval. To assess the pharmaco-economic impact of each of the three study arm strategies. To assess the relationship between disease activity and markers for bone/cartilage turnover. To study and compare the pharmacokinetic changes during the treatment phases of each strategy and relate it to the disease activity. To explore any differences between the patients who presented with their flare at week 14 or at week 22 in the induction period. To assess the predictive value of CRP and ESR, alone, or in combination with clinical measures, to predict (non) reponse to infliximab intensification.;Primary end point(s): The primary endpoint for the study is the change in RA disease activity and the comparison of its measurements between the 2 interventional study groups and the control group. RA disease improvement will be evaluated using the DAS28 scoring system, the EULAR and ACR criteria, quality of life measurement, pain assessment (VAS), and rescue medication consumption. The primary parameter for assessing RA disease improvement, however, is the DAS28-CRP score difference at the end of the study (study week 24) from the score measured at the beginning of the study (study week 0). A difference of 0.6 is considered to be clinically significant. | — |
Countries
Belgium, Denmark, France, Germany, Greece, Netherlands, Portugal, Sweden
Outcome results
None listed