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

• Register: ClinicalTrials.gov
• Last refreshed on: 7 September 2021
• Main ID: NCT03737708
• Date of registration: 08/11/2018
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Korea, Inc.
• Public title: A Study Comparing Biologics + Methotrexate With Biologics + Tacrolimus in Patients With Rheumatoid Arthritis (RA)
• Scientific title: Compare Efficacy and Safety Between Biologics + Methotrexate (MTX) vs Biologics + Tacrolimus (TAC) (Switched From Biologics + Methotrexate (MTX)) in the Patients With Rheumatoid Arthritis (RA): Randomized, Interventional, Open, Active Controlled, Parallel Group, Multicenter-designed, Phase 4 Clinical Trial
• Date of first enrolment: February 13, 2019
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03737708
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Korea, Republic of

Contacts

• Name: Medical Monitor
• Affiliation: Astellas Pharma Korea, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- Subject has a history of active tuberculosis or latent tuberculosis infection without
treatment.

- Subject with mental disorder uncontrolled by drugs.

- Subject with chronic diarrhea, ulcerative stomatitis, gastric ulcer, or ulcerative
colitis.

- Subject with genetic disorders including galactose intolerance, Lapp lactase
deficiency, or glucose-galactose malabsorption.

- Subject with maculopathy, retinal disorders, or clinically significant eye diseases
that may lead to visual disorder.

- Subject with bone marrow disorder, leukopenia, and blood cell disorder such as severe
anemia and thrombocytopenia.

- Subject with a history of major surgery within 12-weeks before screening.

- Subject who were diagnosed with malignant tumors within 5 years before screening or
who need treatment for malignant tumors diagnosed in the past.

- Patients with basal cell and squamous cell carcinomas of the skin or carcinoma in situ
of the cervix uteri that has been excised and cured, may be included on the study at
the discretion of the investigator.

- Female subject who is positive for the serum pregnancy test at Visit 1 among a woman
of childbearing potential (WOCBP) (menopausal is defined as amenorrhea for at least
one year) or not surgically sterile, or is not willing to use appropriate
contraception during the study. Female subject trying to become pregnant or is
currently pregnant or breast feeding.

- Male subject who donates sperm during the treatment period and for at least 30 days
whichever is longer after the final study drug administration.

- Male subject with a pregnant or breastfeeding partner(s) who do not agree to remain
abstinent or use a condom for the duration of the pregnancy, or for the time partner
is breastfeeding, throughout the study period and for 30 days whichever is longer
after the final study drug administration.



Age minimum: 19 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis (RA)

Intervention(s)

Drug: tacrolimus

Biological: adalimumab

Drug: methotrexate

Biological: tocilizumab

Biological: abatacept

Primary Outcome(s)

Change in disease activity score 28 (DAS28) erythrocyte sedimentation rate score (ESR) score at 12 weeks [Time Frame: From baseline (week 1) to week 12]

Secondary Outcome(s)

Change in DAS28 (ESR) score at 8 weeks [Time Frame: From baseline (week 1) to week 8]

Change in DAS28 (ESR) score at 4 weeks [Time Frame: From baseline (week 1) to week 4]

Safety assessed by incidence of treatment emergent adverse events (TEAE) [Time Frame: Up to 12 weeks]

ACR 20 response rate [Time Frame: At 12 weeks]

ACR50 response rate [Time Frame: At 12 weeks]

ACR70 response rate [Time Frame: At 12 weeks]

Number of participants with vital sign abnormalities and /or adverse events (AEs) [Time Frame: Up to 16 weeks]

Safety assessed by incidence of serious adverse events (SAE) [Time Frame: Up to 16 weeks]

DAS28 (ESR) score at 12 weeks [Time Frame: At 12 weeks]

DAS28 (ESR) score at 8 weeks [Time Frame: At 8 weeks]

Number of participants with physical exam abnormalities and/or adverse events (AEs) [Time Frame: Up to 16 weeks]

Disease activity score 28 (DAS28) erythrocyte sedimentation rate (ESR) rate score at 4 weeks [Time Frame: At 4 weeks]

Safety assessed by Adverse Events (AEs) [Time Frame: Up to 16 weeks]

Number of participants with laboratory value abnormalities and/or adverse events (AEs) [Time Frame: Up to 16 weeks]

Secondary ID(s)

506-MA-3187

Source(s) of Monetary Support

Please refer to primary and secondary sponsors