Arthritis, Rheumatoid
Conditions
Brief summary
This trial is extension part of the P04280 (placebo-controlled, double-blind, randomized study of chronic treatment with infliximab in approximately 140 patients, NCT00202852). This study will be conducted at 6 study centers in South Korea. After completion of the last follow-up visit at Week 30 and code break in main double-blind trial, subjects randomized to the placebo group and those who were treated with an infliximab-containing regimen who maintained clinical response at the time of study completion will be provided with open-label infliximab for treatment of their conditions and additional safety data will be collected.
Interventions
BIOLOGICALInfliximab + methotrexate (MTX)
Open label Infliximab infusions at weeks 0, 2, and 6 and every 8 weeks + methotrexate (MTX)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients received placebo in main double-blind study (P04280, NCT00202852) * Patients received Infliximab-containing regimen showing clinical response at week 30 in main double-blind study (P04280) \[Main double-blind study (P04280, NCT00202852) inclusion criteria\] * Diagnosis of rheumatoid arthritis (RA) according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al, 1988). The disease should have been diagnosed \>6 months prior to screening. * Active disease at the time of screening and pre-infusion as defined by: * \>=6 swollen joints * \>=6 tender joints and * 2 of the following: * morning stiffness \>=45 min * erythrocyte sedimentation rate (ESR) \>=28 mm/h * C-reactive protein (CRP) \>=20 mg/L * Men and women, \>=18 to \<=75 years of age * Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, intrauterine device (IUD), barrier method with spermicide, or surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion. * Must have been using oral or parenteral MTX for \>3 months with no break(s) in treatment of \>2 weeks total during this period. Patients must have been on a stable dose of \>=12.5 mg/wk (maximum 20 mg/wk) for at \>4 weeks prior to screening. * Must be on a stable dose of folic acid prophylaxis for \>4 weeks prior to screening. * Patients using oral corticosteroids, must have been on a stable dose of \<=10 mg/day for \>4 weeks prior to screening. If currently not using corticosteroids the patient must have not received corticosteroids for \>4 weeks prior to screening. * If using nonsteroidal anti-inflammatory drugs (NSAIDs), patients should have been on a stable dose for \>4 weeks prior to screening. * The screening laboratory tests must meet the following criteria: * Hemoglobin \>=5.3 mmol/L (\>=8.5 g/dL), providing a low hemoglobin level is not due to nutritional deficiencies or due to diseases other than chronic RA * white blood cell (WBC) \>=3.5 x 10\^9/L (\>=3.5 x 10\^3/mm\^3) * Neutrophils \>=1.5 x 10\^9/L (\>=1.5 x 103/mm\^3) * Platelets \>=100 x 10\^9/L (\>=100 x 103/mm\^3) * Serum transaminase \<=2 times the upper limit of normal * Alkaline phosphatase levels \<=2 times the upper limit of normal * Serum creatinine \<=150 µmol/L (\<=1.7 mg/dL) * Must be able to adhere to the study visit schedule and other protocol requirements. * Must be capable of giving informed consent and the consent must have been obtained prior to any study procedures including wash-out period.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing Any Adverse Event | throughout entire study (61 +/- 28.9 weeks on average) | — |
| Number of Subjects Experiencing Serious Adverse Event | throughout entire study (61 +/- 28.9 weeks on average) | Serious adverse events are defined as death, life-threatening events, persistent or significant disability/incapacity, hospitalization or prolongation of hospitalization and congenital anomalies. |
| Number of Subjects Experiencing Any Infection | throughout entire study (61 +/- 28.9 weeks on average) | — |
Participant flow
Recruitment details
Subjects showing clinical response at Week 30 of a previous double-blind study of infliximab vs placebo (P04280,NCT00202852) were eligible for this study. A total of 105 subjects were eligible (67 from previous placebo & 38 from previous infliximab group) for this extension study, among whom a total of 92 enrolled to participate in the extension.
Pre-assignment details
Of the 92 enrolled subjects, 61 were from the placebo group and 31 from the infliximab group of the previous study.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Infliximab + Methotrexate Open label Infliximab infusions at weeks 0, 2, and 6 and every 8 weeks + methotrexate (MTX) | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Lack of Efficacy | 13 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Open Label Infliximab + Methotrexate |
|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 11.1 |
| Age, Customized <30 years | 2 participants |
| Age, Customized >=70 years | 3 participants |
| Age, Customized Between 30 and less than 40 years | 14 participants |
| Age, Customized Between 40 and less than 50 years | 29 participants |
| Age, Customized Between 50 and less than 60 years | 29 participants |
| Age, Customized Between 60 and less than 70 years | 15 participants |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 92 |
| serious Total, serious adverse events | 12 / 92 |
Outcome results
Primary
Number of Subjects Experiencing Any Adverse Event
Time frame: throughout entire study (61 +/- 28.9 weeks on average)
Population: All participants were included regardless of how long they stayed in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Infliximab + Methotrexate | Number of Subjects Experiencing Any Adverse Event | 76 participants |
Primary
Number of Subjects Experiencing Any Infection
Time frame: throughout entire study (61 +/- 28.9 weeks on average)
Population: All participants were included regardless of how long they stayed in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Infliximab + Methotrexate | Number of Subjects Experiencing Any Infection | 41 participants |
Primary
Number of Subjects Experiencing Serious Adverse Event
Serious adverse events are defined as death, life-threatening events, persistent or significant disability/incapacity, hospitalization or prolongation of hospitalization and congenital anomalies.
Time frame: throughout entire study (61 +/- 28.9 weeks on average)
Population: All participants were included regardless of how long they stayed in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Infliximab + Methotrexate | Number of Subjects Experiencing Serious Adverse Event | 12 participants |