A Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate

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

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: ASP5094; Other: Methotrexate therapy; Drug: Placebo

Detailed Description

The study drug will be intravenously administered.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Asahikawa, Japan
    • Site JP00002
  • Asahikawa, Japan
    • Site JP00027
  • Beppu, Japan
    • Site JP00029
  • Chiba, Japan
    • Site JP00015
  • Fukuoka, Japan
    • Site JP00008
  • Fukuoka, Japan
    • Site JP00009
  • Fukuoka, Japan
    • Site JP00026
  • Ichinomiya, Japan
    • Site JP00016
  • Kanuma, Japan
    • Site JP00012
  • Kawachinagano, Japan
    • Site JP00028
  • Kitamoto, Japan
    • Site JP00005
  • Kobe, Japan
    • Site JP00025
  • Kobe, Japan
    • Site JP00030
  • Kumamoto, Japan
    • Site JP00010
  • Kyoto, Japan
    • Site JP00006
  • Meguro, Japan
    • Site JP00018
  • Nagano, Japan
    • Site JP00020
  • Nagoya, Japan
    • Site JP00014
  • Oita, Japan
    • Site JP00011
  • Okayama, Japan
    • Site JP00022
  • Osaki, Japan
    • Site JP00003
  • Sagamihara, Japan
    • Site JP00019
  • Sanuki, Japan
    • Site JP00007
  • Sapporo, Japan
    • Site JP00001
  • Shimonoseki, Japan
    • Site JP00023
  • Shizuoka, Japan
    • Site JP00021
  • Takasaki, Japan
    • Site JP00004
  • Tomakomai, Japan
    • Site JP00017
  • Toyohashi, Japan
    • Site JP00013
  • Tsukuba, Japan
    • Site JP00024
  • Yokohama, Japan
    • Site JP00031

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP5094 Group; To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.	Drug: ASP5094; intravenously administration; Other: Methotrexate 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.
Placebo Comparator: Placebo Group; To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate.	Other: Methotrexate 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.; Drug: Placebo; intravenously administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50 response rate	To assess ACR (American College of Rheumatology) 50 for efficacy	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50 response rate	To assess ACR (American College of Rheumatology) 50 for efficacy	Up to Week 16
ACR20 response rate	To assess ACR (American College of Rheumatology) 20 for efficacy	Up to Week 16
ACR70 response rate	To assess ACR (American College of Rheumatology) 70 for efficacy	Up to Week 16
Change from baseline in DAS28-CRP score	To assess DAS28-CRP (Disease Activity Score28 - C-reactive protein) for efficacy	Baseline and Up to Week 16
Change from baseline in DAS28-ESR score	To assess DAS28-ESR (Disease Activity Score28 - Erythrocyte sedimentation rate) for efficacy	Baseline and Up to Week 16
Change from baseline in Tender Joint Count (68 joints)	To assess Tender Joint Count for efficacy	Baseline and Up to Week 16
Change from baseline in Swollen Joint Count (66 joints)	To assess Swollen Joint Count for efficacy	Baseline and Up to Week 16
Percentage of subjects achieving DAS28-CRP score for remission (<2.6)	To assess DAS28-CRP score for efficacy	Up to Week 16
Percentage of subjects achieving DAS28-ESR score for remission (<2.6)	To assess DAS28-ESR score for efficacy	Up to Week 16
Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2)	To assess DAS28-CRP score for efficacy	Up to Week 16
Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2)	To assess DAS28-ESR score for efficacy	Up to Week 16
Change from baseline in CRP	To assess CRP (C-reactive protein) for efficacy	Baseline and Up to Week 16
Change from baseline in ESR	To assess ESR (Erythrocyte sedimentation rate) for efficacy	Baseline and Up to Week 16
Percentage of subjects achieving EULAR response criteria of "Good Response"	To assess EULAR (European league Against Rheumatism) response criteria for efficacy	Up to Week 16
Percentage of subjects achieving EULAR response criteria of "Good Response" or "Moderate Response"	To assess EULAR response criteria for efficacy	Up to Week 16
Percentage of subjects achieving ACR/EULAR score for remission	To assess ACR/EULAR remission for efficacy	Up to Week 16
Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)	To assess SDAI (Simplified Disease Activity Index) score for efficacy	Up to Week 16
Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission)	To assess CDAI (Clinical Disease Activity Index) score for efficacy	Up to Week 16
Change from baseline for the HAQ-DI	To assess HAQ-DI (Health Assessment Questionnaire - Disability Index) for efficacy	Baseline to Up to Week 16
Safety assessed by incidence of adverse events	Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA).	Up to Week 16
Safety assessed by laboratory tests: Hematology	To assess hematology as a criteria of safety variables.	Up to Week 16
Safety assessed by laboratory tests: Biochemistry	To assess Biochemistry as a criteria of safety variables.	Up to Week 16
Safety assessed by laboratory tests: Urinalysis	To assess Urinalysis as a criteria of safety variables.	Up to Week 16
Safety assessed by vital signs: Body temperature	To assess the vital sign as a criteria of safety variables.	Up to Week 16
Safety assessed by vital signs: Sitting blood pressure	To assess the vital sign as a criteria of safety variables.	Up to Week 16
Safety assessed by vital signs: pulse rate	To assess the vital sign as a criteria of safety variables.	Up to Week 16
Safety assessed by weight	To assess the weight as a criteria of safety variables.	Up to Week 16
Safety assessed by standard 12-lead electrocardiogram	To assess the cardiovascular system functioning as a criteria of safety variables.	Up to Week 16
Serum concentration of ASP5094	To assess Serum concentration of ASP5094 for pharmacokinetics	Up to Week 16
Serum concentration of TNF-α	To assess TNF-α (Tumor Necrosis Factor-α) for pharmacodynamics	Up to Week 16
Serum concentration of MMP3	To assess MMP3 (Matrix metalloproteinase 3) for pharmacodynamics	Up to Week 16
Serum concentration of IL-6	To assess IL-6 (Interleukin-6) for pharmacodynamics	Up to Week 16
Anti-ASP5094 anti-bodies	To assess Anti-ASP5094 anti-bodies for immunogenicity	Up to Week 16

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2017
• Primary Completion (Actual): September 19, 2018
• Study Completion (Actual): October 16, 2018

Study Registration Dates

• First Submitted: August 20, 2017
• First Submitted That Met QC Criteria: August 20, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Methotrexate; Arthritis, Rheumatoid; ASP5094
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Methotrexate
• Other Study ID Numbers: 5094-CL-0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No