A Study to Investigate Efficacy and Safety of AZD1163 in Participants With Rheumatoid Arthritis

AZD1163 is a novel bispecific antibody that inhibits the activity of extracellular peptidyl arginine deiminase 2 (PAD2) and peptidyl arginine deiminase 4 (PAD4) enzymes, which are responsible for protein citrullination. In RA, citrullinated proteins lead to the production of pathogenic anti-citrullinated peptide antibodies (ACPA).

This is a Phase II, randomised, double-blind, multicentre, 4 arm placebo-controlled study designed to evaluate the efficacy and safety of AZD1163 in ACPA + adults with moderate-to-severely active RA on standard of care (SoC) (conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] or tumour necrosis factor inhibitor [TNFi] +/- csDMARD).

The study will have a screening period followed by a randomisation period wherein approximately 320 participants will be randomised in a 1:1:1:1 ratio to receive study intervention.

Participants will receive subcutaneous (SC) injection of one of three different doses of AZD1163 or placebo, along with SoC until Week 24 followed by a safety follow-up (FU) period of 28 weeks.

• Inclusion

• Diagnosed with adult-onset RA as defined by the 2010 ACR/EULAR classification criteria for at least 12 weeks prior to screening.
• Moderately-to-severely active RA as defined by: a. >= 6 swollen joints on 66SJC and >= 6 tender joints on 68TJC; b. CRP > upper limit of normal.
• Have a positive ACPA at screening.
• A history of inadequate response, or loss of response, or intolerance to: a. at least one csDMARD treatment, AND/OR b. At least one and at most 2 TNFi.
• A history of at least 12 weeks treatment and >= 4 weeks stable on a csDMARD and/or SC TNFi prior to the day of randomisation.
• Exclusion

• History or evidence of an alternate autoimmune or other condition that could confound the diagnosis of RA. Participants with RA and secondary Sjogren's disease are eligible.
• Have received or planning to receive any biologic DMARDs (except for TNFi) or targeted synthetic DMARDs.