Protocol Version 1.0 - Original protocol

Protocol Version 2.0 - This amendment made the following changes: • Updated the objectives and estimands to include participants with confirmed condition of IA synovitis on baseline MRI. • Updated the primary endpoint to add that the successful composite clinical response at Weeks 4 and 8 according to the criteria for ACR20 were to be achieved without discontinuing treatment due to tolerability issues or lack of efficacy or requiring any increase in RA medications. • Endpoint descriptions have been modified: o Addition of DAS28-hsCRP <3.2 at Weeks 4, 8, and 12. o Addition of change in CARLOS from baseline to Week 12. o Change in ACPA levels from screening to Week 12. • Inclusion criteria updated to include: o Acceptance of one repeat assessment for CRP as per the investigator’s discretion if all other eligibility criteria were met. o Updates to the conditions for discontinuation of oral DMARDs for ≥8 weeks prior to baseline visit to include oral cyclosporine. o Updates to the language in the criteria for participants taking NSAIDs or acetaminophen. • Exclusion criteria updated to include: o Clarification on the clinically significant features of arthroses that could interfere with study assessments and objectives. o Updates to the language on male and female contraception. o The exclusion due to major surgery for RA within 56 days prior to the baseline visit was deleted. o History of other major surgery timelines were changed from screening to baseline. • Study design was updated to change the study intervention dosage instructions at home during study visits 3, 4 and 5. • Efficacy assessments had the following minor changes: o VAS value for measuring disease activity, arthritis pain, and assessment of health removed. o Included that the CARLOS determined by MRI will be assessed using a previously validated 9-point CARLOS scale. • Sample size summary was modified. • Changes made to the statistical analyses.