Rheumatoid Arthritis
Conditions
Brief summary
This Phase IIIb, randomized, multi-national, multi-center, blinded study of Infliximab (IFX) in subjects aged 18 and older with active RA is being conducted to assess whether increasing either the infusion dose or infusion frequency in patients presenting with a disease flare after an initial response to infliximab results in a significant improvement in disease activity. Subjects responding to an initial infliximab treatment regimen, who flare during continuation of treatment at 3 mg/kg administered every 8 weeks, will be randomly assigned to one of 3 different dosing regimens of infliximab and will be treated for 4 or 5 consecutive infusions for a total duration of 24 weeks. The infliximab control group and the infliximab increased dose group are evaluator and subject-blinded. The increased frequency group is not blinded. Clinical assessments of disease activity will be based the European League Against Rheumatism (EULAR) criteria for response. Safety parameters will be assessed at every infusion. A disease flare is defined by an increase in DAS28 with 0.6 or more at screening, when compared to the DAS28 score measured immediately prior to the last Remicade® infusion and depends upon the actual score as well. Since prior to enrollment, the subject received Remicade® as per routine clinical practice, the days on which infusions were administered and assessments are done during the induction period do not have to be exactly at Week 2, 6 and 14. * Drug: Infliximab Control (double-blinded) * Drug: Infliximab Increased Dose (double-blinded) * Drug: Infliximab Increased Frequency (open-label)
Interventions
DRUGInfliximab Increased Frequency
Continuing the same dose of 3 mg/kg infliximab, but at every 6 weeks for 24 weeks
DRUGInfliximab Increased Dose
3 mg/kg infliximab + 1 extra vial (100 mg) infliximab every 8 weeks for 24 weeks
DRUGInfliximab Control
Continuation of infliximab 3 mg/kg every 8 weeks for 24 weeks
Sponsors
Integrated Therapeutics Group
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* aged 18 years or more * with RA according to ACR criteria * presented with a disease flare after initial response to infliximab, with both response and flare being defined using the DAS28 score (EULAR criteria) * received the standard Remicade® dosing schedule per the EU label (3 mg/kg at Weeks 0, 2, 6, \[and 14\]) * an initial response documented by moderate or good DAS28 improvement (EULAR criteria) from Week 0 to Week 6 or 14.
Exclusion criteria
* a female who is, or intends to become, pregnant during or within 6 months of the end of the study, is nursing or not using adequate contraceptive measures * has not observed the designated periods for concomitant medications * used any investigational medical product within 30 days prior to Baseline * 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 * rheumatic disease other than RA or has any systemic inflammatory condition with signs and symptoms that might confound the evaluations of safety and toxicity * allergic reaction/sensitivity to the study drug or its excipients that requires corticosteroid pre-infusion medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score. | Between Screening (Week <=1) and Week 24 | Descriptive summary of DAS28 (Disease Activity Score Based on 28 Joint Count)change from Baseline to the end of study (Week 24) in the population with available data at both Baseline and Week 24 (increased dose group, n=5; increased frequency group, n=7; and control group, n=5). DAS28 is a unit scale from 2.0 (best value) to 10.0 (worst value). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Increased Dose 3 mg/kg infliximab + 1 extra vial (100 mg) infliximab every 8 weeks | 14 |
| Increased Frequency Continuing the same dose of 3 mg/kg infliximab, but at every 6 weeks | 11 |
| Control Continuation of infliximab 3 mg/kg every 8 weeks | 18 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 2 |
| Overall Study | Lack of Efficacy | 2 | 2 | 3 |
| Overall Study | Protocol Violation | 4 | 0 | 2 |
Baseline characteristics
| Characteristic | Increased Dose | Increased Frequency | Control | Total |
|---|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 13 | 58.6 years STANDARD_DEVIATION 16.1 | 57.7 years STANDARD_DEVIATION 12.3 | 58.3 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 14 Participants | 34 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 14 | 5 / 11 | 5 / 18 |
| serious Total, serious adverse events | 2 / 14 | 0 / 11 | 2 / 18 |
Outcome results
Primary
Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score.
Descriptive summary of DAS28 (Disease Activity Score Based on 28 Joint Count)change from Baseline to the end of study (Week 24) in the population with available data at both Baseline and Week 24 (increased dose group, n=5; increased frequency group, n=7; and control group, n=5). DAS28 is a unit scale from 2.0 (best value) to 10.0 (worst value).
Time frame: Between Screening (Week <=1) and Week 24
Population: Intent-to-treat population; subjects with available data at both Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Increased Dose | Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score. | -0.4 Score on a Scale | Standard Deviation 1.27 |
| Increased Frequency | Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score. | -1.6 Score on a Scale | Standard Deviation 1.23 |
| Control | Change in Disease Activity Score Based on 28 Joint Count (DAS28) Score. | -1.0 Score on a Scale | Standard Deviation 1.9 |