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Title A Randomized, Double-Blind Trial Assessing the Impact of Methotrexate Discontinuation on the Efficacy of Subcutaneous Tocilizumab with Methotrexate Therapy [Protocol #: ML28776]
Therapeutic Area Rheumatoid Arthritis, Arthritis
Principal Investigator Steven C. Vlad, MD, PhD
Min Age 18 Years
Gender Both
Contact Megan Erickson
More Information


This is a randomized, multicenter, double-blind, parallel-group, 52-week study (plus 8-week follow-up) of tocilizumab (TCZ) + methotrexate (MTX) in rheumatoid arthritis (RA) patients who are inadequate responders (IR) to MTX. The primary efficacy objective of this study is to evaluate if the discontinuation of MTX is noninferior to continuing MTX as a strategy for maintaining disease activity in patients with MTX-IR RA who achieve a Disease Activity Score (DAS28) ≤ 3.2 following intial treatment with subcutaneous (SC) TCZ + MTX. Secondary efficacy objectives are 1) to compare the proportion of patients with an increase in DAS28 in the randomized patients who do or do not discontinue MTX and 2) to explore the effects on disease activity when the dosing schedule is changed from TCZ 162 mg SC every 2 weeks (Q2W) to every week (QW) in patients who have not achieved DAS ≤ 3.2 at Week 12 on the Q2W dose. The safety objective is to assess adverse events (AEs), serious adverse events (SAEs), AEs of special interest, immunogenicity, and laboratory parameters, throughout the study period in patients who do or do not discontinue MTX. Patients will be initiated into the study on a dose of TCZ 162 mg SC QW (those weighing < 100 kg) or Q2W (those weighing ≥ 100 kg) and will remain on a stable pre-baseline MTX dose of at least 15 mg/week orally (PO). After 24 weeks, DAS28 scores will be evaluated. Patients with DAS28 ≤ 3.2 will be blindly randomized to either continue receiving a stable dose of MTX or to switch to a matching dose of placebo. Patients not achieving DAS28 ≤ 3.2 will be assigned to an open-label, non-randomized arm to continue receiving open-label TCZ + MTX until Week 52, and those patients still receiving TCZ 162 mg Q2W will increase dosing frequency to QW. The patients in this arm will not be included in the primary analysis cohort, but will be analyzed separately to explore the effects of dose escalation and/or longer-term exposure to TCZ.

Study Details

Inclusion Criteria

  • Currently experiencing moderate to severe RA
  • Currently taking oral methotrexate
  • Able to speak, write, and understand English

Exclusion Criteria

  • Intolerance to oral methotrexate
  • Previously received medications like abatacept, rituximab, tofacitinib, or anakinra
  • Diagnosed with other autoimmune diseases (such as lupus, inflammatory bowel disease, psoriasis, and multiple sclerosis)

Study Requirements

The study requires 16 visits over about 64 weeks. Participants will be asked to provide a blood sample at each visit, and will also undergo physical examination, electrocardiogram (ECG), rheumatoid arthritis examination, and be asked to complete questionnaires at various study visits. Participants will receive their first subcutaneous (under-the-skin) dose of study drug at the clinic, and then will perform weekly or biweekly injections on their own at home.