Arthritis, Rheumatoid
Conditions
Keywords
Arthritis, Rheumatoid
Brief summary
This is a Phase 3b, multicenter study of the efficacy of golimumab 2 mg/kg IV in subjects with active rheumatoid arthritis who are receiving methotrexate and have inadequate disease control (defined as an erythrocyte sedimentation rate \[ESR\]-based Disease Activity Score in 28 joints \[DAS28\] ≥ 3.2 and ≥ 4 swollen and ≥ 4 tender joints) despite current anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks. To be eligible for participation, subjects must have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, who have since exhibited a diminished response despite continued treatment. It is estimated that 200 subjects will be enrolled in the study at approximately 85 global sites.
Detailed description
The study employs an open-label active switch design that moves subjects from infliximab to golimumab 2 mg/kg IV. In general, subjects eligible for the study include men or women who are currently receiving infliximab in actual clinical practice who are at least 18 years of age with active rheumatoid arthritis, and have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, but now exhibit a diminished response and inadequate disease control despite continued treatment. Subjects must have received infliximab in combination with methotrexate for a minimum of 9 months prior to the first screening visit. The screening visit will occur sometime between Week -12 and Week -10. Consenting subjects who meet screening criteria will receive their final dose of infliximab at Week -8 as part of actual clinical practice. Golimumab IV treatment, which will be supplied by the sponsor, will be received at Weeks 0, 4, 12, 20, and 28. The primary endpoint is at Week 24, the final efficacy assessment is at Week 32, and a follow-up safety assessment by telephone is at Week 44. There will be a maximum of 36 weeks between the last infliximab infusion at Week -8 and the last infusion of golimumab at Week 28. The duration of study participation is expected to be a maximum of 56 weeks (including the Screening Period, 32 weeks of golimumab treatment and assessment, and a 12-week safety follow-up).
Interventions
BIOLOGICALGolimumab 2 mg/kg IV
Study drug (golimumab 2 mg/kg IV) will be administered as an intravenous (IV) infusion at Weeks 0, 4, 12, 20 and 28.
Sponsors
Janssen Biotech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria include (but not limited to): * Have a diagnosis of Rheumatoid Arthritis (according to the revised 1987 criteria of the American Rheumatism Association). * Treatment with infliximab and methotrexate for \>= 9 months, (with stable doses of methotrexate over last 16 weeks of 7.5 mg/week to 25 mg/week) and (anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks). * Disease Activity Score 28 (DAS28) ≥ 3.2 based on Erythrocyte Sedimentation Rate (ESR) at Week -8 and Week 0. * Swollen joint count (SJC) ≥ 4 and tender joint count (TJC) ≥ 4 at Week - 8 and at Week 0. * Prior response confirmed by physician. Major
Exclusion criteria
include (but not limited to): * Have a history of latent or active granulomatous infection, including histoplasmosis, or Have a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to the first screening visit or during the Screening Period. * Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening. * Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis. * Have previously received more than 1 of the currently approved subcutaneous (SC) administered anti-TNFα agents, etanercept, certolizumab pegol, golimumab, or adalimumab. * Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of the study agent. * Weight less than 35 kg or greater than 110 kg (less than 77 pounds or greater than 242 pounds).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24 | Week 24 | The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and erythrocyte sedimentation rate (ESR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an ACR 20 Response at Week 24 With Confirmed Presence of Antibodies to Infliximab | Week 24 | The ACR 20 Response is defined as \>= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR. |
| Percentage of Participants Who Acheived ACR 20 Response at Week 24 With Trough Infliximab Levels Below the Lower Limit of Quantification (LLOQ) | Week 24 | The ACR 20 Response is defined as \>= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR. |
Countries
Canada, United States
Participant flow
Pre-assignment details
The study was terminated early due to low recruitment; only 7 participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Golimumab Participants received golimumab 2 milligram per kilogram (mg/kg) intravenously (IV) at Weeks 0, 4, 12, 20, and 28. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study termination | 7 |
Baseline characteristics
| Characteristic | Golimumab |
|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 11.06 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and erythrocyte sedimentation rate (ESR).
Time frame: Week 24
Population: Due to early study termination, data for this outcome measure was not collected and therefore the analyses could not be conducted.
Secondary
Percentage of Participants Who Acheived ACR 20 Response at Week 24 With Trough Infliximab Levels Below the Lower Limit of Quantification (LLOQ)
The ACR 20 Response is defined as \>= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR.
Time frame: Week 24
Population: Due to early study termination, data for this outcome measure was not collected and therefore the analyses could not be conducted.
Secondary
Percentage of Participants Who Achieved an ACR 20 Response at Week 24 With Confirmed Presence of Antibodies to Infliximab
The ACR 20 Response is defined as \>= 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (010 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and ESR.
Time frame: Week 24
Population: Due to early study termination, data for this outcome measure was not collected and therefore the analyses could not be conducted.