Rheumatoid Arthritis (RA)
Conditions
Keywords
Methotrexate, Arthritis, Rheumatoid, ASP5094
Brief summary
The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of ASP5094 in patients with rheumatoid arthritis (RA) treated with background methotrexate (MTX).
Detailed description
The study drug will be intravenously administered.
Interventions
DRUGASP5094
intravenously administration
DRUGPlacebo
intravenously administration
OTHERMethotrexate therapy
MTX must have been continuously orally administered for at least 90 days prior to screening, with stable dosage for at least 28 days prior to screening, and will be continuously administered with the same dosage throughout the study period.
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 ACR/European League Against Rheumatism (EULAR) criteria at least 6 months prior to screening. * Subject meets the 1991 ACR Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III at screening. * At screening and baseline, subject has active RA as evidenced by both of the following: * ≥ 6 tender/painful joints (using 68-joint assessment) * ≥ 6 swollen joints (using 66-joint assessment) * Subject meets the criterion for a CRP level (Latex Agglutination method) at screening. * Subject who has continuously received Methotrexate for at least 90 days prior to screening and who is able to continue a stable dose of Methotrexate from at least 28 days prior to screening throughout the study period.
Exclusion criteria
* Subject has deviated from the criteria for previous and concomitant treatment before baseline. * Subject has an ongoing infection requiring antibiotics. * Subject is determined to be an inadequate responder to a prior biologic disease modifying antirheumatic drugs (DMARDs) or Janus kinase (JAK) inhibitors. * Subject has participated in previous ASP5094 clinical trial. * Subject has participated in a clinical trial or post-marketing clinical study of another ethical drug or medical device within 12 weeks (84 days). * Subject has another inflammatory arthritis than RA, or any other articular symptom which may affect on joint assessment. * Subject meets any of the criteria for laboratory values at screening. * Subject has a positive T-SPOT or QuantiFERON Gold test within 90 days prior to screening or at screening. * Subject has a history of or concurrent malignant tumor. * Subject has autoimmune disease except for RA or any severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or mental illness. * Subject has a history of clinically significant allergy. * Subject has clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening. * Subject has a history of Human Immunodeficiency Virus (HIV) infection. * Subject had surgery within 30 days prior to screening or has a planned elective surgery. * Subject has a wound that is currently healing at baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACR50 response rate | Week 12 | To assess ACR (American College of Rheumatology) 50 for efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACR20 response rate | Up to Week 16 | To assess ACR (American College of Rheumatology) 20 for efficacy |
| ACR70 response rate | Up to Week 16 | To assess ACR (American College of Rheumatology) 70 for efficacy |
| Change from baseline in DAS28-CRP score | Baseline and Up to Week 16 | To assess DAS28-CRP (Disease Activity Score28 - C-reactive protein) for efficacy |
| Change from baseline in DAS28-ESR score | Baseline and Up to Week 16 | To assess DAS28-ESR (Disease Activity Score28 - Erythrocyte sedimentation rate) for efficacy |
| Change from baseline in Tender Joint Count (68 joints) | Baseline and Up to Week 16 | To assess Tender Joint Count for efficacy |
| Change from baseline in Swollen Joint Count (66 joints) | Baseline and Up to Week 16 | To assess Swollen Joint Count for efficacy |
| Percentage of subjects achieving DAS28-CRP score for remission (<2.6) | Up to Week 16 | To assess DAS28-CRP score for efficacy |
| Percentage of subjects achieving DAS28-ESR score for remission (<2.6) | Up to Week 16 | To assess DAS28-ESR score for efficacy |
| Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2) | Up to Week 16 | To assess DAS28-CRP score for efficacy |
| Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2) | Up to Week 16 | To assess DAS28-ESR score for efficacy |
| Change from baseline in CRP | Baseline and Up to Week 16 | To assess CRP (C-reactive protein) for efficacy |
| Change from baseline in ESR | Baseline and Up to Week 16 | To assess ESR (Erythrocyte sedimentation rate) for efficacy |
| Percentage of subjects achieving EULAR response criteria of Good Response | Up to Week 16 | To assess EULAR (European league Against Rheumatism) response criteria for efficacy |
| Percentage of subjects achieving EULAR response criteria of Good Response or Moderate Response | Up to Week 16 | To assess EULAR response criteria for efficacy |
| Percentage of subjects achieving ACR/EULAR score for remission | Up to Week 16 | To assess ACR/EULAR remission for efficacy |
| Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission) | Up to Week 16 | To assess SDAI (Simplified Disease Activity Index) score for efficacy |
| ACR50 response rate | Up to Week 16 | To assess ACR (American College of Rheumatology) 50 for efficacy |
| Change from baseline for the HAQ-DI | Baseline to Up to Week 16 | To assess HAQ-DI (Health Assessment Questionnaire - Disability Index) for efficacy |
| Safety assessed by incidence of adverse events | Up to Week 16 | Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA). |
| Safety assessed by laboratory tests: Hematology | Up to Week 16 | To assess hematology as a criteria of safety variables. |
| Safety assessed by laboratory tests: Biochemistry | Up to Week 16 | To assess Biochemistry as a criteria of safety variables. |
| Safety assessed by laboratory tests: Urinalysis | Up to Week 16 | To assess Urinalysis as a criteria of safety variables. |
| Safety assessed by vital signs: Body temperature | Up to Week 16 | To assess the vital sign as a criteria of safety variables. |
| Safety assessed by vital signs: Sitting blood pressure | Up to Week 16 | To assess the vital sign as a criteria of safety variables. |
| Safety assessed by vital signs: pulse rate | Up to Week 16 | To assess the vital sign as a criteria of safety variables. |
| Safety assessed by weight | Up to Week 16 | To assess the weight as a criteria of safety variables. |
| Safety assessed by standard 12-lead electrocardiogram | Up to Week 16 | To assess the cardiovascular system functioning as a criteria of safety variables. |
| Serum concentration of ASP5094 | Up to Week 16 | To assess Serum concentration of ASP5094 for pharmacokinetics |
| Serum concentration of TNF-α | Up to Week 16 | To assess TNF-α (Tumor Necrosis Factor-α) for pharmacodynamics |
| Serum concentration of MMP3 | Up to Week 16 | To assess MMP3 (Matrix metalloproteinase 3) for pharmacodynamics |
| Serum concentration of IL-6 | Up to Week 16 | To assess IL-6 (Interleukin-6) for pharmacodynamics |
| Anti-ASP5094 anti-bodies | Up to Week 16 | To assess Anti-ASP5094 anti-bodies for immunogenicity |
| Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission) | Up to Week 16 | To assess CDAI (Clinical Disease Activity Index) score for efficacy |
Countries
Japan
Outcome results
None listed