Rheumatoid Arthritis
Conditions
Keywords
Auto-immune Disease, Arthritis, Rheumatoid Arthritis
Brief summary
The purpose of this study is to determine if the use of sub-cutaneous (SC) abatacept provides any structural benefit in patients with rheumatoid arthritis who have failed prior use of TNF therapy.
Detailed description
Results in the literature suggest the structural benefits of intravenous (IV) abatacept as measured by high and low field MRI and X-ray in patients with rheumatoid arthritis who have previously failed clinical treatment with TNF agents. This study attempts to measure the structural benefits of SC abatacept in a similar cohort of patients while at the same time comparing the structural findings with clinical outcome measurements as collected at corresponding time points with an automated patient and physician disease activity scoring system of 28 joints (DAS28).
Interventions
BIOLOGICALabatacept
Abatacept administered SC weekly at 125 mg dose
Sponsors
Bristol-Myers Squibb
Arthritis & Rheumatic Disease Specialties Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Able and willing to give written informed consent * Patients must have a diagnosis of rheumatoid arthritis \> 3 months * Patients must have been receiving methotrexate for 12 weeks prior to screening at a dose of 10mg - 25 mg weekly. * Patient must have had an inadequate response after receiving or previously receiving one (1) but no more than two (2) anti-TNF biologic agents * Age \>/= 18 yrs * Must have active RA as defined by a DAS28 (Erythrocyte sedimentation rate) score \>4.4 * Must have synovitis of at least two joints in one hand/wrist at screening and baseline * Must have a negative Pregnancy test and use adequate method of contraception throughout the trial * Stable use of Corticosteroids is permitted * Stable use of Non-steroidal anti-inflammatory drugs is permitted
Exclusion criteria
* Functional Class IV * Pregnancy or breastfeeding * History of any other inflammatory arthritis * Sexually active patients who are not using acceptable birth control * Subjects who have undergone metacarpophalangeal (MCP) arthroplasty or anticipate the need for such a procedure * Subjects with a history of cancer in the last five years other than non melanoma skin cancers * Subjects who are unable to comply with study and followup procedures * Subjects who have current or severe symptoms of renal, hepatic, hematologic, gastrointestinal, pulmonary cardiac, neurologic, or cerebral disease * Subjects who currently abuse drugs or alcohol * Subjects with evidence of active or latent bacterial or viral infections at the time of enrollment * Subjects who have received live vaccines within 4 months of first dose of study medication * Subjects with herpes zoster or cytomegalovirus that resolved less than two months prior to dosing * Subjects at risk for tuberculosis (TB). Specifically excluded will be subjects with a history of active TB within the last 3 years and subjects with latent TB must have a negative chest X-ray and be started on treatment for at least 28 days prior to dosing. * Prior treatment with Rituximab within 12 months * Prior treatment with more than 2 TNFs * Intramuscular(IM), Intravenous(IV) Intra-articular (IA) corticosteroids within 28 days prior to baseline * Subjects who have a metal device affected by MRI (e.g. any type of electronic, mechanical or magnetic implant, metal slivers, metal objects, cardioverter defibrillator) * Subjects who have received any disease modifying agent (DMARD) other than methotrexate within the past 28 days prior to baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Improvement in Bone Edema/Osteitis on Low-field MRI in Rheumatoid Arthritis Patients on Weekly SC Abatacept in Combination With Methotrexate Over a 12-month Period. | MRIs at Baseline and Week 48 | bone edema/osteitis using low-field MRI analysis of 25 anatomical locations in the wrist and hand and scoring the volume of the original articular bone in 0.5 increments from 0-3, with each increment in the scale representing 33% of the volume of the peripheral 1 cm of original (eroded + residual) articular bone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With an Improvement in DAS Score Were Considered Responders at Week 48 | The DAS 28 score will be performed at baseline and 48 | Patient with a positive change in DAS score were considered responders . The DAS score is calculated using the number of tender and swollen joints based upon a 28 joint count, the ESR in mm/hr., and the physician global score |
| To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | Patient DAS 28 scores will be measured at baseline and weeks 12, 24, 48 and disease activity will be recorded at Week 48 | DAS 28\> 5.1=high disease activity DAS28 \<3.2=low disease activity DAS28 \<2.6=remission Criteria used in formula are number of tender joints based upon 28 joints, number of swollen joints based on 28 joints, ESR in mm/hr and patient global health core based on 0-10 mm |
| Number of Patients With Adverse Events | all adverse events will be captured from Day 1 up to 52 weeks | site will report the number of patients with adverse envents from Day 1 up to 52 weeks |
| the Clinical Outcomes Measurements (American College of Rheumatology Activity Scoring, Health Assessment The Number of Patients With a Clinical Response at Week 24 and 48 | week 24 and Week 48 | Patient with a positive change in DAS score were considered responders . The DAS score is calculated using the number of tender and swollen joints based upon a 28 joint count, the ESR in mm/hr., and the physician global score (1-10 cm). Total maximum score was at high disease activity at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abatacept open label use of abatacept for 12 months
abatacept: Abatacept administered SC weekly at 125 mg dose | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Abatacept |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 57 years |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Number of Participants With an Improvement in Bone Edema/Osteitis on Low-field MRI in Rheumatoid Arthritis Patients on Weekly SC Abatacept in Combination With Methotrexate Over a 12-month Period.
bone edema/osteitis using low-field MRI analysis of 25 anatomical locations in the wrist and hand and scoring the volume of the original articular bone in 0.5 increments from 0-3, with each increment in the scale representing 33% of the volume of the peripheral 1 cm of original (eroded + residual) articular bone.
Time frame: MRIs at Baseline and Week 48
Population: osteitis on the MRIs from 27 patients at baseline and week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With an Improvement in Bone Edema/Osteitis on Low-field MRI in Rheumatoid Arthritis Patients on Weekly SC Abatacept in Combination With Methotrexate Over a 12-month Period. | 27 participants |
Secondary
Number of Patients With Adverse Events
site will report the number of patients with adverse envents from Day 1 up to 52 weeks
Time frame: all adverse events will be captured from Day 1 up to 52 weeks
Population: There were 34 enrolled patients with 7 patients who early termed so analysis was performed on 27 patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Patients With Adverse Events | 0 participants |
Secondary
Patients With an Improvement in DAS Score Were Considered Responders at Week 48
Patient with a positive change in DAS score were considered responders . The DAS score is calculated using the number of tender and swollen joints based upon a 28 joint count, the ESR in mm/hr., and the physician global score
Time frame: The DAS 28 score will be performed at baseline and 48
Population: There were 34 enrolled patients with 7 patients who early termed so analysis was performed on 27 patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Patients With an Improvement in DAS Score Were Considered Responders at Week 48 | 25 participants |
Secondary
the Clinical Outcomes Measurements (American College of Rheumatology Activity Scoring, Health Assessment The Number of Patients With a Clinical Response at Week 24 and 48
Patient with a positive change in DAS score were considered responders . The DAS score is calculated using the number of tender and swollen joints based upon a 28 joint count, the ESR in mm/hr., and the physician global score (1-10 cm). Total maximum score was at high disease activity at baseline.
Time frame: week 24 and Week 48
Population: There were 34 enrolled patients with 7 patients who early termed so analysis was performed on 27 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept | the Clinical Outcomes Measurements (American College of Rheumatology Activity Scoring, Health Assessment The Number of Patients With a Clinical Response at Week 24 and 48 | clinical response at 6 months | 20 participants |
| Abatacept | the Clinical Outcomes Measurements (American College of Rheumatology Activity Scoring, Health Assessment The Number of Patients With a Clinical Response at Week 24 and 48 | clinical response at 12 months | 25 participants |
Secondary
To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24
DAS 28\> 5.1=high disease activity DAS28 \<3.2=low disease activity DAS28 \<2.6=remission Criteria used in formula are number of tender joints based upon 28 joints, number of swollen joints based on 28 joints, ESR in mm/hr and patient global health core based on 0-10 mm
Time frame: Patient DAS 28 scores will be measured at baseline and weeks 12, 24, 48 and disease activity will be recorded at Week 48
Population: the number of participants who reached remission, low disease activity, moderate disease activity and high disease activity will be determined as based upon the DAS scale
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | clinical remission at week 12 | 2 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | low disease activity at week 12 | 2 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | mod disease activity at week 12 | 12 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | high disease activity at week 12 | 11 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | clinical remission at week 24 | 1 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | low disease activity at week 24 | 2 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | moderate disease activity at week 24 | 14 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | high disease activity at week 24 | 8 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | clinical remission at week 48 | 4 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | low disease activity at week 48 | 6 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | moderate disease activity at week 48 | 8 participants |
| Abatacept | To Measure the Change From Baseline in Patient DAS 28 Scores at Baseline and Weeks 12, 24 | high disease activity at week 48 | 7 participants |