Complementary Herbal Approach to Rheumatoid Management Study (CHARMS)

Prior treatment

• Previous lack of efficacy to Si Miao Xiao Bi Tang.
• Concurrent use of other immunosuppressant medications, except MTX and protocol allowed doses of steroids.
• Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point administration of corticosteroids in the preceding 4 weeks prior to the Baseline Visit.
• Subject has been treated with any investigational drug within a minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the Baseline Visit or is currently enrolling in another clinical study.
• Receipt of any live vaccine within 1 month prior to the Screening Visit, or expected need of live vaccination during study participation including up to 1 month after the last dose of study drug.
• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Day 1 or oral anti-infectives within 14 days prior to the Baseline Visit.

Other illness

• History of inflammatory joint disease other than RA. Secondary Sjogren's Syndrome is permitted.
• Infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses, untreated malignancy, or evidence of active or untreated latent tuberculosis.
• History of clinically significant hematologic, pulmonary, renal, hepatic, or psychiatric disease that would interfere with the subject's participation in this study.
• Any arrhythmia on baseline/screening ECG.

Lab values

• Any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
  • Evidence of hematopoietic disorder or hemoglobin \<9 g/dL
  • White blood cell count \<3.0 x 10\^9/L (\<3000/mm\^3)
  • Absolute neutrophil count \<1.2 x 10\^9/L (\<1000/mm\^3)
  • Platelet count \<100 x 10\^9/L (\<100,000/mm\^3)
  • Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal (ULN)
  • Estimated glomerular filtration rate of less than 60 mL/min

Other

• Not able to provide informed consent.
• Pregnant or breastfeeding females.
• Females of childbearing potential not willing to use contraceptive methods which, in the opinion of the investigator, are effective and adequate while on the study. Female subjects who are not of childbearing potential must meet at least one of the following criteria: (a) Have undergone a documented hysterectomy and/or bilateral oophorectomy; or (b) Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause.
• Been diagnosed with G6PD deficiency.
• Subjects who are taking TCM supplements regularly (daily) and not willing to stop intake.

• Patients between the ages of 21 and 70 years, and diagnosed with RA by a rheumatologist and fulfilling the 2010 ACR/EULAR classification criteria for RA.
• Active disease with DAS28 ESR ≥3.2 at screening, with at least 6 swollen joints out of 66 and at least 6 tender joints out of 68.
• Receiving stable doses of methotrexate therapy for at least 3 months, and on stable dose for at least 4 weeks before trial entry ( ≥10mg per week), either subcutaneous or orally.
• Stable doses of non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, or oral corticosteroids (equivalent to prednisone ≤ 10 mg) for at least 4 weeks prior to first dose of study medication.
• Except for methotrexate, patients must have discontinued all csDMARDs, including, but not limited to: hydroxychloroquine, sulfasalazine, leflunomide prior to first dose of study medication as specified below:
  • ≥ 4 weeks prior to Baseline Visit for sulfasalazine and hydroxychloroquine
  • ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure (i.e., 11 days with cholestyramine, or 30 days washout with activated charcoal)
• A negative urine pregnancy test for women of childbearing potential on Day 1 (prior to administration of first dose of study drug).
• Use of a reliable method of contraception by all female patients of childbearing potential and male patients with procreative capacity during the study and up to 3 months after the last dose of the study medication.