A Study Comparing Biologics + Methotrexate With Biologics + Tacrolimus in Patients With Rheumatoid Arthritis (RA)

NCT03737708 | Completed Phase 4

• 1 other identifier: 506-MA-3187
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to compare the efficacy of Biologics + Methotrexate with Biologics + Tacrolimus measured by the disease activity score 28 (DAS28) erythrocyte sedimentation rate (ESR) and the American College of Rheumatology (ACR) scores. The study will also assess the safety of the combinations.

Conditions

Rheumatoid Arthritis (RA)

Keywords

tacrolimus; abatacept; Prograf; adalimumab; methotrexate; tocilizumab; FK506

Outcome Measures

Primary Outcomes (1)

• Change in disease activity score 28 (DAS28) erythrocyte sedimentation rate score (ESR) score at 12 weeks

  DAS28-ESR will be calculated using data from tender joint count (TJC) (28 joints), swollen joint count (SJC) (28 joints), ESR and Subject's Global Assessment of Arthritis (SGA) with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA. High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.

  From baseline (week 1) to week 12

Secondary Outcomes (14)

• Disease activity score 28 (DAS28) erythrocyte sedimentation rate (ESR) rate score at 4 weeks

  At 4 weeks

• DAS28 (ESR) score at 8 weeks

  At 8 weeks

• DAS28 (ESR) score at 12 weeks

  At 12 weeks

• Change in DAS28 (ESR) score at 4 weeks

  From baseline (week 1) to week 4

• Change in DAS28 (ESR) score at 8 weeks

  From baseline (week 1) to week 8

Study Arms (2)

tacrolimus + biologics

EXPERIMENTAL

Participants will receive tacrolimus daily for 12 weeks. In addition, each participant will be administered one of adalimumab, tocilizumab, or abatacept for 12 weeks.

Drug: tacrolimus; Biological: adalimumab; Biological: tocilizumab; Biological: abatacept

methotrexate + biologics

ACTIVE COMPARATOR

Participants will receive methotrexate weekly for 12 weeks. In addition, each participant will be administered one of adalimumab, tocilizumab, or abatacept for 12 weeks.

Drug: methotrexate; Biological: adalimumab; Biological: tocilizumab; Biological: abatacept

Interventions

tacrolimus DRUG

Administered orally

Also known as: FK506, Prograf

tacrolimus + biologics

methotrexate DRUG

Administered orally

methotrexate + biologics

adalimumab BIOLOGICAL

Administered as subcutaneous injection

methotrexate + biologics; tacrolimus + biologics

tocilizumab BIOLOGICAL

Administered by intravenous injection

methotrexate + biologics; tacrolimus + biologics

abatacept BIOLOGICAL

Administered by intravenous injection

methotrexate + biologics; tacrolimus + biologics

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with rheumatoid arthritis (RA) diagnosed by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR).
• Subjects who have been treated with combination therapy of one of biologic agent (adalimumab, tocilizumab, or abatacept) + methotrexate (MTX) over 2 months prior to Visit 1.
• Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) ≥ 3.2 at screening and baseline.
• Subject agrees not to participate in another interventional study while participating in the present study.

You may not qualify if:

• Subjects with a past history of allergic reaction to Investigational Product or Comparative Drug used in this study.
• Subjects who were given tacrolimus (TAC) within three months before participation in this study.
• Subjects who have been treated with combination therapy of one of biologic agent (adalimumab, tocilizumab, or abatacept) + MTX exceeds 3 months at Baseline.
• Subjects who were already taking 20 mg of MTX at Screening Period.
• Subjects who were given the prohibited concomitant medications prior to randomization.
• Subjects with a medical history of clinically significant blood, gastrointestinal, endocrine, lung, nerve, or brain diseases at screening.
• Subjects with a medical history of clinically significant liver, kidney, or heart diseases:
• Liver disease: Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) \> 3 × upper limit of normal (ULN) at screening, viral infection, nonviral infection, and liver cirrhosis;
• Kidney disease: serum creatinine \> 2.0 mg/dL at screening;
• Heart disease: heart failure of ≥ The New York Heart Association class 3, arrhythmia or ischemic heart disease requiring treatment, and QTc interval \> 450 ms on Electrocardiogram (ECG) at screening;
• Subjects with a history of uncontrolled diabetes (glycosylated hemoglobin \> 8.5%).
• Subjects with hyperkalemia or serum potassium level \> ULN of site reference ranges at screening.
• Subjects with severe respiratory disease or chronic generalized infectious disease.
• Subject who have a history of chronic infection or severe or life-threatening infection within 24 weeks before the baseline visit.
• Subject who are known to be infected by Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C.

Sponsors & Collaborators

• Astellas Pharma Korea, Inc.: lead

Study Sites (10)

Site KR82003

Daegu, South Korea

Location

Site KR82007

Daegu, South Korea

Location

Site KR82006

Daejeon, South Korea

Location

Site KR82002

Incheon, South Korea

Location

Site KR82009

Seongnam, South Korea

Location

Site KR82001

Seoul, South Korea

Location

Site KR82005

Seoul, South Korea

Location

Site KR82010

Seoul, South Korea

Location

Site KR82012

Seoul, South Korea

Location

Site KR82013

Suwon, South Korea

Location

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Tacrolimus; Methotrexate; Adalimumab; tocilizumab; Abatacept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoconjugates

Study Officials

• Medical Monitor

  Astellas Pharma Korea, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 9, 2018
• Study Start: February 13, 2019
• Primary Completion: June 16, 2020
• Study Completion: June 16, 2020
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10)