Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, injection, golimumab, simponi
Brief summary
The purpose of this study is to evaluate the safety and efficacy of golimumab in Chinese patients with rheumatoid arthritis.
Detailed description
Golimumab is a type of tumor necrosis factor (TNF)-inhibitor. TNF is a naturally occurring substance in the body, and this substance may cause long-term inflammation. Golimumab may help fight disease by blocking the activity of TNF in the body and reducing inflammation and pain. Each patient who is allowed to join the study will be put into a group randomly, like flipping a coin. Patients may get either golimumab or placebo (which looks like the drug being studied but has no active ingredients, for example a sugar pill). The chance that the patient will get golimumab is 1 to 1, a 50% chance to receive golimumab and a 50% chance to receive placebo. If the patient does not have an improvement in their joints at the Week 16 visit compared to when they entered the study, and are in Group 1 (placebo group), the patient will receive golimumab 50 mg every 4 weeks starting at Week 16. If the patient is in Group 2 (golimumab 50 mg), the patient will continue to receive golimumab every 4 weeks starting at Week 16. If the patient is in Group 1 and is still receiving placebo injections, because there was improvement in their joints at Week 16, the patient will receive golimumab 50 mg every 4 weeks starting from Week 24. If the patient is in Group 2 (golimumab 50 mg) or is already receiving golimumab injections at week 24, the patient will continue to receive golimumab every 4 weeks. Safety will be monitored throughout the study, including drawing blood and looking at laboratory tests, vital signs (e.g., blood pressure), and the frequency and type of adverse events (side effects). The patient will be in the study approximately 56 weeks. Patients will receive placebo or active compound (golimumab 50 mg subcutaneous injections) every four weeks from randomization (Week 0) until Week 48.
Interventions
DRUGGolimumab
50 mg subcutaneous (SC) injection every 4 weeks for up to 48 weeks
DRUGPlacebo
Placebo SC injections at Weeks 0, 4, 8, 12, 16, and Week 20 followed by golimumab 50 mg SC injections at Week 24 and every 4 weeks thereafter up to Week 48.
DRUGMethotrexate (MTX)
A stable dose of MTX (oral or injectable) will be administered to participants according to the local prescribing guidelines for up to 48 weeks.
Sponsors
Schering-Plough
Centocor, Inc.
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
\- Diagnosis of rheumatoid arthritis for at least 6 months * Be on a stable dose of methotrexate for 4 weeks * Have at least 4 swollen and 4 tender joints
Exclusion criteria
* Prior exposure to biologic anti-TNFalpha agents * Inflammatory diseases other than rheumatoid arthritis * Treatment with Disease Modifying Anti-rheumatic drug (DMARDs)/systemic immunosuppressives other than methotrexate during the 4 weeks prior to the first administration of study agent * History of, or ongoing, chronic or recurrent infectious disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14 | Week 14 | ACR 20 response is defined as \>= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein) | Week 14 | DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A DAS28 (using CRP) responder is defined as a participant with a DAS28 response of Good or Moderate at Week 14. A Good response is defined as a patient with a DAS28 score of \<= 3.2 at Week 14 with improvement from Baseline in DAS28 score of \> 1.2. A Moderate response was defined as a patient with DAS28 score of \>3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of \>0.6 to \>1.2 The table below shows the number of participants in each treatment group who were DAS28 responders at Week 14. |
| American College of Rheumatology 20 Response, Using CRP, at Week 24 | Week 24 | ACR 20 response is defined as \>= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity. |
| HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline | Baseline to Week 24 | The HAQ assesses the degree of difficulty a person has in accomplishing tasks in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). The full range of the HAQ scale is 0-24 with 0 being the best possible outcome. The HAQ score is calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3 with 0 being the best possible outcome (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, or 3=unable to do). The mean change from baseline at Week 24 in HAQ score is provided below for each treatment group. A negative change from baseline is indicative of a lesser degree of difficulty in accomplishing tasks assessed in the HAQ. |
Countries
China
Participant flow
Pre-assignment details
In this trial, 264 participants were randomly assigned to the 2 treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Group I: Placebo + MTX -> Golimumab 50 mg + MTX Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 48 if early escape; golimumab 50 mg SC injections every 4 weeks from Week 24 to Week 48 if not early escape. In addition, participants received a stable dose of methotrexate (MTX) capsules (\>= 7.5 mg/week and \<= 20 mg/week). | 132 |
| Group II: Golimumab 50 mg + MTX Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 48; In addition, participants received a stable dose of methotrexate (MTX) capsules (\>= 7.5 mg/week and \<= 20 mg/week). | 132 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not treated | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Group I: Placebo + MTX -> Golimumab 50 mg + MTX | Group II: Golimumab 50 mg + MTX | Total |
|---|---|---|---|
| Age Continuous | 46.7 years STANDARD_DEVIATION 12.16 | 47.7 years STANDARD_DEVIATION 11.46 | 47.2 years STANDARD_DEVIATION 11.81 |
| Sex: Female, Male Female | 104 Participants | 110 Participants | 214 Participants |
| Sex: Female, Male Male | 28 Participants | 22 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 128 | 35 / 131 |
| serious Total, serious adverse events | 4 / 128 | 8 / 131 |
Outcome results
Primary
American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14
ACR 20 response is defined as \>= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.
Time frame: Week 14
Population: Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo + MTX | American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14 | 21 Number of participants |
| Group II: Golimumab 50 mg + MTX | American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14 | 54 Number of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
American College of Rheumatology 20 Response, Using CRP, at Week 24
ACR 20 response is defined as \>= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.
Time frame: Week 24
Population: Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo + MTX | American College of Rheumatology 20 Response, Using CRP, at Week 24 | 21 Number of participants |
| Group II: Golimumab 50 mg + MTX | American College of Rheumatology 20 Response, Using CRP, at Week 24 | 56 Number of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein)
DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A DAS28 (using CRP) responder is defined as a participant with a DAS28 response of Good or Moderate at Week 14. A Good response is defined as a patient with a DAS28 score of \<= 3.2 at Week 14 with improvement from Baseline in DAS28 score of \> 1.2. A Moderate response was defined as a patient with DAS28 score of \>3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of \>0.6 to \>1.2 The table below shows the number of participants in each treatment group who were DAS28 responders at Week 14.
Time frame: Week 14
Population: Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo + MTX | Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein) | 40 Number of participants |
| Group II: Golimumab 50 mg + MTX | Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein) | 86 Number of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline
The HAQ assesses the degree of difficulty a person has in accomplishing tasks in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). The full range of the HAQ scale is 0-24 with 0 being the best possible outcome. The HAQ score is calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3 with 0 being the best possible outcome (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, or 3=unable to do). The mean change from baseline at Week 24 in HAQ score is provided below for each treatment group. A negative change from baseline is indicative of a lesser degree of difficulty in accomplishing tasks assessed in the HAQ.
Time frame: Baseline to Week 24
Population: Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I: Placebo + MTX | HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline | 0.1525 Scores on a scale | Standard Deviation 0.69164 |
| Group II: Golimumab 50 mg + MTX | HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline | -0.2623 Scores on a scale | Standard Deviation 0.56767 |
p-value: <0.001ANOVA