Efficacy and Safety Study of Tacrobell to Treat Rheumatoid Arthritis (TIARA)

Phase IV STudy of Tacrobell in Active Rheumatoid Arthritis

The aims of this study are to assess the efficacy and safety of tacrolimus in patients with active rheumatoid arthritis(RA). EULAR(European League Against Rheumatism) response at week 24 compared to baseline will be evaluated to assess the efficacy of Tacrolimus.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tacrolimus with Methotrexate

Detailed Description

A Phase IV, Open labeled, Multi-Center Trial to Assess the Efficacy and Safety of Tacrolimus(Tacrobell®)in patients with active rheumatoid arthritis(RA).

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female aged ≥20years
• Signed and dated informed consent document indicating that the patient
• Women of childbearing potential must have a negative serum or urine pregnancy test at the screening visit. Except in the case of surgically sterile or amenorrhea for one year.
• Female patients must agree to use adequate contraception measures during the period of therapy which should be continued for 4 weeks.
• have RA and meet all of the following criteria; RA occurring ≥ 3months and less than 15 years and diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis; Active RA patients with MTX and among them who has insufficiency response to DMARDs as defined DAS28>3.2 in active RA patient. Insufficiency response is defined despite MTX therapy for > 12 weeks, RA activity≥ more than moderate and confirmable during 12 weeks, sequence of taking MTX >7.5mg/week for more than 6 weeks; ESR≥28mm/h or CRP≥1.0mg/dl; Tender Joint Counts must be more than 6 and Swollen Joint Counts must be more than 3

Exclusion Criteria:

• Inflammatory joint diseases, Systematic inflammatory disease
• Prosthesis and had an event of infected in it.
• Medical history of chronic infection, moderate infection or possibly to life threatening or signs and symptoms of serious infection.
• Patients have received treatment with a live vaccine from baseline within 8 weeks.
• HBsAg positive and hepatitis C virus positive patient.
• Patients have a history of malignancy. (But, carcinoma in situ of the uterine cervix or basal cell carcinoma have been treated is allowed within 5years)
• Patients have cardiovascular disease or associated disease which is not controlled.
• uncontrollable blood sugar(HbA1C ≥8%) or required insulin.
• Patients with a history of operation on index knee joint which could have influence on the result and need to have surgery as determined by investigator.
• At screening, patients have laboratory result as defined by ; white blood cell(WBC) < 3,500/mm3, Absolute Neutrophil Count(ANC) < 1,500/mm3, Hemoglobin < 8.5g/dl, Platelet count(PLT) < 100,000/mm3, Serum creatinine >1.5*upper limit of normal or 2mg/dl, Total bilirubin > 2*upper limit of normal, aspartate aminotransferase(AST) > 2*upper limit of normal, alanine aminotransferase(ALT) > 2*upper limit of normal, alkaline phosphatase(ALP) > 2*upper limit of normal
• Patients on any other clinical trial or experimental treatment in the past 8weeks
• An impossible one who participates in clinical trial by investigator's decision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus with Methotrexate; Subjects have tacrolimus per oral once daily with methotrexate for 24weeks. Tacrolimus increased dosing regimen: 1mg for 0~4 weeks, 2mg for 4 weeks~8 weeks, 3mg for 8 weeks~24 weeks	Drug: Tacrolimus with Methotrexate; Tacrolimus 1 mg for 0~week4, 2mg for week4~week8, 3mg for week8~week24 with MTX ≤20mg/week; Other Names: TacroBell® with MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline European League Against Rheumatism(EULAR) response at 24weeks	baseline, 24weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline Simplified Disease Activity Index(SDAI) at 24weeks	baseline, 24weeks
Change from baseline Korean Health Assessment Questionnaire(KHAQ-20) at 24weeks	baseline, 24weeks
Change from baseline Erythrocyte Sedimentation Rate(ESR) at 16weeks	baseline, 16weeks
Change from baseline Erythrocyte Sedimentation Rate(ESR) at 24weeks	baseline, 24eeks
Change from baseline C-Reactive Protein(CRP) at 16weeks	baseline, 16weeks
Change from baseline C-Reactive Protein(CRP) at 24weeks	baseline, 24weeks
Change from baseline European League Against Rheumatism(EULAR) response at 16weeks	baseline, 16weeks

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Chair: Seung -Jae Hong, phD, Dr, Kyung Hee University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 9, 2012
• First Posted (Estimate): December 11, 2012

Study Record Updates

• Last Update Posted (Estimate): August 11, 2015
• Last Update Submitted That Met QC Criteria: August 9, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; tacrolimus; RA; Disease Activity Score 28; EULAR
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Methotrexate; Tacrolimus
• Other Study ID Numbers: m308RAP11M