Back to resultsA Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate
Primary Purpose
Rheumatoid Arthritis (RA)
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
ASP5094
Placebo
Methotrexate therapy
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis (RA) focused on measuring Methotrexate, Arthritis, Rheumatoid, ASP5094
Eligibility Criteria
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.
Sites / Locations
- Site JP00002
- Site JP00027
- Site JP00029
- Site JP00015
- Site JP00008
- Site JP00009
- Site JP00026
- Site JP00016
- Site JP00012
- Site JP00028
- Site JP00005
- Site JP00025
- Site JP00030
- Site JP00010
- Site JP00006
- Site JP00018
- Site JP00020
- Site JP00014
- Site JP00011
- Site JP00022
- Site JP00003
- Site JP00019
- Site JP00007
- Site JP00001
- Site JP00023
- Site JP00021
- Site JP00004
- Site JP00017
- Site JP00013
- Site JP00024
- Site JP00031
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ASP5094 Group
Placebo Group
Arm Description
To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.
To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.
Outcomes
Primary Outcome Measures
ACR50 response rate
To assess ACR (American College of Rheumatology) 50 for efficacy
Secondary Outcome Measures
ACR50 response rate
To assess ACR (American College of Rheumatology) 50 for efficacy
ACR20 response rate
To assess ACR (American College of Rheumatology) 20 for efficacy
ACR70 response rate
To assess ACR (American College of Rheumatology) 70 for efficacy
Change from baseline in DAS28-CRP score
To assess DAS28-CRP (Disease Activity Score28 - C-reactive protein) for efficacy
Change from baseline in DAS28-ESR score
To assess DAS28-ESR (Disease Activity Score28 - Erythrocyte sedimentation rate) for efficacy
Change from baseline in Tender Joint Count (68 joints)
To assess Tender Joint Count for efficacy
Change from baseline in Swollen Joint Count (66 joints)
To assess Swollen Joint Count for efficacy
Percentage of subjects achieving DAS28-CRP score for remission (<2.6)
To assess DAS28-CRP score for efficacy
Percentage of subjects achieving DAS28-ESR score for remission (<2.6)
To assess DAS28-ESR score for efficacy
Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2)
To assess DAS28-CRP score for efficacy
Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2)
To assess DAS28-ESR score for efficacy
Change from baseline in CRP
To assess CRP (C-reactive protein) for efficacy
Change from baseline in ESR
To assess ESR (Erythrocyte sedimentation rate) for efficacy
Percentage of subjects achieving EULAR response criteria of "Good Response"
To assess EULAR (European league Against Rheumatism) response criteria for efficacy
Percentage of subjects achieving EULAR response criteria of "Good Response" or "Moderate Response"
To assess EULAR response criteria for efficacy
Percentage of subjects achieving ACR/EULAR score for remission
To assess ACR/EULAR remission for efficacy
Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)
To assess SDAI (Simplified Disease Activity Index) score for efficacy
Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission)
To assess CDAI (Clinical Disease Activity Index) score for efficacy
Change from baseline for the HAQ-DI
To assess HAQ-DI (Health Assessment Questionnaire - Disability Index) for efficacy
Safety assessed by incidence of adverse events
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA).
Safety assessed by laboratory tests: Hematology
To assess hematology as a criteria of safety variables.
Safety assessed by laboratory tests: Biochemistry
To assess Biochemistry as a criteria of safety variables.
Safety assessed by laboratory tests: Urinalysis
To assess Urinalysis as a criteria of safety variables.
Safety assessed by vital signs: Body temperature
To assess the vital sign as a criteria of safety variables.
Safety assessed by vital signs: Sitting blood pressure
To assess the vital sign as a criteria of safety variables.
Safety assessed by vital signs: pulse rate
To assess the vital sign as a criteria of safety variables.
Safety assessed by weight
To assess the weight as a criteria of safety variables.
Safety assessed by standard 12-lead electrocardiogram
To assess the cardiovascular system functioning as a criteria of safety variables.
Serum concentration of ASP5094
To assess Serum concentration of ASP5094 for pharmacokinetics
Serum concentration of TNF-α
To assess TNF-α (Tumor Necrosis Factor-α) for pharmacodynamics
Serum concentration of MMP3
To assess MMP3 (Matrix metalloproteinase 3) for pharmacodynamics
Serum concentration of IL-6
To assess IL-6 (Interleukin-6) for pharmacodynamics
Anti-ASP5094 anti-bodies
To assess Anti-ASP5094 anti-bodies for immunogenicity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03257852
Brief Title
A Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate
Official Title
A Phase 2a, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
September 29, 2017 (Actual)
Primary Completion Date
September 19, 2018 (Actual)
Study Completion Date
October 16, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis (RA)
Keywords
Methotrexate, Arthritis, Rheumatoid, ASP5094
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ASP5094 Group
Arm Type
Experimental
Arm Description
To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.
Intervention Type
Drug
Intervention Name(s)
ASP5094
Intervention Description
intravenously administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
intravenously administration
Intervention Type
Other
Intervention Name(s)
Methotrexate therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
ACR50 response rate
Description
To assess ACR (American College of Rheumatology) 50 for efficacy
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
ACR50 response rate
Description
To assess ACR (American College of Rheumatology) 50 for efficacy
Time Frame
Up to Week 16
Title
ACR20 response rate
Description
To assess ACR (American College of Rheumatology) 20 for efficacy
Time Frame
Up to Week 16
Title
ACR70 response rate
Description
To assess ACR (American College of Rheumatology) 70 for efficacy
Time Frame
Up to Week 16
Title
Change from baseline in DAS28-CRP score
Description
To assess DAS28-CRP (Disease Activity Score28 - C-reactive protein) for efficacy
Time Frame
Baseline and Up to Week 16
Title
Change from baseline in DAS28-ESR score
Description
To assess DAS28-ESR (Disease Activity Score28 - Erythrocyte sedimentation rate) for efficacy
Time Frame
Baseline and Up to Week 16
Title
Change from baseline in Tender Joint Count (68 joints)
Description
To assess Tender Joint Count for efficacy
Time Frame
Baseline and Up to Week 16
Title
Change from baseline in Swollen Joint Count (66 joints)
Description
To assess Swollen Joint Count for efficacy
Time Frame
Baseline and Up to Week 16
Title
Percentage of subjects achieving DAS28-CRP score for remission (<2.6)
Description
To assess DAS28-CRP score for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving DAS28-ESR score for remission (<2.6)
Description
To assess DAS28-ESR score for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2)
Description
To assess DAS28-CRP score for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2)
Description
To assess DAS28-ESR score for efficacy
Time Frame
Up to Week 16
Title
Change from baseline in CRP
Description
To assess CRP (C-reactive protein) for efficacy
Time Frame
Baseline and Up to Week 16
Title
Change from baseline in ESR
Description
To assess ESR (Erythrocyte sedimentation rate) for efficacy
Time Frame
Baseline and Up to Week 16
Title
Percentage of subjects achieving EULAR response criteria of "Good Response"
Description
To assess EULAR (European league Against Rheumatism) response criteria for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving EULAR response criteria of "Good Response" or "Moderate Response"
Description
To assess EULAR response criteria for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving ACR/EULAR score for remission
Description
To assess ACR/EULAR remission for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)
Description
To assess SDAI (Simplified Disease Activity Index) score for efficacy
Time Frame
Up to Week 16
Title
Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission)
Description
To assess CDAI (Clinical Disease Activity Index) score for efficacy
Time Frame
Up to Week 16
Title
Change from baseline for the HAQ-DI
Description
To assess HAQ-DI (Health Assessment Questionnaire - Disability Index) for efficacy
Time Frame
Baseline to Up to Week 16
Title
Safety assessed by incidence of adverse events
Description
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA).
Time Frame
Up to Week 16
Title
Safety assessed by laboratory tests: Hematology
Description
To assess hematology as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by laboratory tests: Biochemistry
Description
To assess Biochemistry as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by laboratory tests: Urinalysis
Description
To assess Urinalysis as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by vital signs: Body temperature
Description
To assess the vital sign as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by vital signs: Sitting blood pressure
Description
To assess the vital sign as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by vital signs: pulse rate
Description
To assess the vital sign as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by weight
Description
To assess the weight as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Safety assessed by standard 12-lead electrocardiogram
Description
To assess the cardiovascular system functioning as a criteria of safety variables.
Time Frame
Up to Week 16
Title
Serum concentration of ASP5094
Description
To assess Serum concentration of ASP5094 for pharmacokinetics
Time Frame
Up to Week 16
Title
Serum concentration of TNF-α
Description
To assess TNF-α (Tumor Necrosis Factor-α) for pharmacodynamics
Time Frame
Up to Week 16
Title
Serum concentration of MMP3
Description
To assess MMP3 (Matrix metalloproteinase 3) for pharmacodynamics
Time Frame
Up to Week 16
Title
Serum concentration of IL-6
Description
To assess IL-6 (Interleukin-6) for pharmacodynamics
Time Frame
Up to Week 16
Title
Anti-ASP5094 anti-bodies
Description
To assess Anti-ASP5094 anti-bodies for immunogenicity
Time Frame
Up to Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Inc
Official's Role
Study Director
Facility Information:
Facility Name
Site JP00002
City
Asahikawa
Country
Japan
Facility Name
Site JP00027
City
Asahikawa
Country
Japan
Facility Name
Site JP00029
City
Beppu
Country
Japan
Facility Name
Site JP00015
City
Chiba
Country
Japan
Facility Name
Site JP00008
City
Fukuoka
Country
Japan
Facility Name
Site JP00009
City
Fukuoka
Country
Japan
Facility Name
Site JP00026
City
Fukuoka
Country
Japan
Facility Name
Site JP00016
City
Ichinomiya
Country
Japan
Facility Name
Site JP00012
City
Kanuma
Country
Japan
Facility Name
Site JP00028
City
Kawachinagano
Country
Japan
Facility Name
Site JP00005
City
Kitamoto
Country
Japan
Facility Name
Site JP00025
City
Kobe
Country
Japan
Facility Name
Site JP00030
City
Kobe
Country
Japan
Facility Name
Site JP00010
City
Kumamoto
Country
Japan
Facility Name
Site JP00006
City
Kyoto
Country
Japan
Facility Name
Site JP00018
City
Meguro
Country
Japan
Facility Name
Site JP00020
City
Nagano
Country
Japan
Facility Name
Site JP00014
City
Nagoya
Country
Japan
Facility Name
Site JP00011
City
Oita
Country
Japan
Facility Name
Site JP00022
City
Okayama
Country
Japan
Facility Name
Site JP00003
City
Osaki
Country
Japan
Facility Name
Site JP00019
City
Sagamihara
Country
Japan
Facility Name
Site JP00007
City
Sanuki
Country
Japan
Facility Name
Site JP00001
City
Sapporo
Country
Japan
Facility Name
Site JP00023
City
Shimonoseki
Country
Japan
Facility Name
Site JP00021
City
Shizuoka
Country
Japan
Facility Name
Site JP00004
City
Takasaki
Country
Japan
Facility Name
Site JP00017
City
Tomakomai
Country
Japan
Facility Name
Site JP00013
City
Toyohashi
Country
Japan
Facility Name
Site JP00024
City
Tsukuba
Country
Japan
Facility Name
Site JP00031
City
Yokohama
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
IPD Sharing Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
IPD Sharing Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
33087159
Citation
Takeuchi T, Tanaka Y, Erdman J, Kaneko Y, Saito M, Higashitani C, Smulders R, Lademacher C. ASP5094, a humanized monoclonal antibody against integrin alpha-9, did not show efficacy in patients with rheumatoid arthritis refractory to methotrexate: results from a phase 2a, randomized, double-blind, placebo-controlled trial. Arthritis Res Ther. 2020 Oct 21;22(1):252. doi: 10.1186/s13075-020-02336-3.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=348
Description
Link to results on the Astellas Clinical Study Results website
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate
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