Clinical trial NCT03257852: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis (RA)
Keywords: Methotrexate
Arthritis, Rheumatoid
ASP5094
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2017-08-22
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: ACR50 response rate
timeFrame: Week 12
Secondary outcomes:
measure: ACR50 response rate
timeFrame: Up to Week 16
measure: ACR20 response rate
timeFrame: Up to Week 16
measure: ACR70 response rate
timeFrame: Up to Week 16
measure: Change from baseline in DAS28-CRP score
timeFrame: Baseline and Up to Week 16
measure: Change from baseline in DAS28-ESR score
timeFrame: Baseline and Up to Week 16
measure: Change from baseline in Tender Joint Count (68 joints)
timeFrame: Baseline and Up to Week 16
measure: Change from baseline in Swollen Joint Count (66 joints)
timeFrame: Baseline and Up to Week 16
measure: Percentage of subjects achieving DAS28-CRP score for remission (<2.6)
timeFrame: Up to Week 16
measure: Percentage of subjects achieving DAS28-ESR score for remission (<2.6)
timeFrame: Up to Week 16
measure: Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2)
timeFrame: Up to Week 16
measure: Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2)
timeFrame: Up to Week 16
measure: Change from baseline in CRP
timeFrame: Baseline and Up to Week 16
measure: Change from baseline in ESR
timeFrame: Baseline and Up to Week 16
measure: Percentage of subjects achieving EULAR response criteria of "Good Response"
timeFrame: Up to Week 16
measure: Percentage of subjects achieving EULAR response criteria of "Good Response" or "Moderate Response"
timeFrame: Up to Week 16
measure: Percentage of subjects achieving ACR/EULAR score for remission
timeFrame: Up to Week 16
measure: Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)
timeFrame: Up to Week 16
measure: Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission)
timeFrame: Up to Week 16
measure: Change from baseline for the HAQ-DI
timeFrame: Baseline to Up to Week 16
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 16
measure: Safety assessed by laboratory tests: Hematology
timeFrame: Up to Week 16
measure: Safety assessed by laboratory tests: Biochemistry
timeFrame: Up to Week 16
measure: Safety assessed by laboratory tests: Urinalysis
timeFrame: Up to Week 16
measure: Safety assessed by vital signs: Body temperature
timeFrame: Up to Week 16
measure: Safety assessed by vital signs: Sitting blood pressure
timeFrame: Up to Week 16
measure: Safety assessed by vital signs: pulse rate
timeFrame: Up to Week 16
measure: Safety assessed by weight
timeFrame: Up to Week 16
measure: Safety assessed by standard 12-lead electrocardiogram
timeFrame: Up to Week 16
measure: Serum concentration of ASP5094
timeFrame: Up to Week 16
measure: Serum concentration of TNF-α
timeFrame: Up to Week 16
measure: Serum concentration of MMP3
timeFrame: Up to Week 16
measure: Serum concentration of IL-6
timeFrame: Up to Week 16
measure: Anti-ASP5094 anti-bodies
timeFrame: Up to Week 16
Other outcomes:
Locations:
city: Asahikawa
country: Japan
facility: Site JP00002
city: Asahikawa
country: Japan
facility: Site JP00027
city: Beppu
country: Japan
facility: Site JP00029
city: Chiba
country: Japan
facility: Site JP00015
city: Fukuoka
country: Japan
facility: Site JP00008
city: Fukuoka
country: Japan
facility: Site JP00009
city: Fukuoka
country: Japan
facility: Site JP00026
city: Ichinomiya
country: Japan
facility: Site JP00016
city: Kanuma
country: Japan
facility: Site JP00012
city: Kawachinagano
country: Japan
facility: Site JP00028
city: Kitamoto
country: Japan
facility: Site JP00005
city: Kobe
country: Japan
facility: Site JP00025
city: Kobe
country: Japan
facility: Site JP00030
city: Kumamoto
country: Japan
facility: Site JP00010
city: Kyoto
country: Japan
facility: Site JP00006
city: Meguro
country: Japan
facility: Site JP00018
city: Nagano
country: Japan
facility: Site JP00020
city: Nagoya
country: Japan
facility: Site JP00014
city: Oita
country: Japan
facility: Site JP00011
city: Okayama
country: Japan
facility: Site JP00022
city: Osaki
country: Japan
facility: Site JP00003
city: Sagamihara
country: Japan
facility: Site JP00019
city: Sanuki
country: Japan
facility: Site JP00007
city: Sapporo
country: Japan
facility: Site JP00001
city: Shimonoseki
country: Japan
facility: Site JP00023
city: Shizuoka
country: Japan
facility: Site JP00021
city: Takasaki
country: Japan
facility: Site JP00004
city: Tomakomai
country: Japan
facility: Site JP00017
city: Toyohashi
country: Japan
facility: Site JP00013
city: Tsukuba
country: Japan
facility: Site JP00024
city: Yokohama
country: Japan
facility: Site JP00031
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
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.