Safety, tolerability, and efficacy of the PD-1 agonist antibody JNJ-67484703 in adults with active rheumatoid arthritis: results of a multicenter, double-blind, placebo-controlled, randomized, multiple-dose phase Ib study.

Background: Programmed cell death protein 1 (PD-1) is associated with the immunopathology of rheumatoid arthritis (RA). JNJ-67484703 is a humanized IgG anti-PD-1 agonist antibody. Objectives: To report results of a phase Ib study evaluating the safety, tolerability, and disease-related outcomes of JNJ-67484703 in adults with active rheumatoid arthritis. Design: A randomized, double-blind, placebo-controlled, multiple-dose, phase Ib study in adults with active RA who were inadequately controlled on conventional synthetic disease-modifying antirheumatic drugs. Methods: JNJ-67484703 at doses of 2 or 3 mg/kg or placebo was administered by subcutaneous injection for 10 weeks (on weeks 0, 1, 2, 4, 6, 8, and 10). Safety was assessed for the first 6 participants in the 2 mg/kg group to determine if enrollment would proceed to the 3 mg/kg dose. The primary endpoint was the proportion of participants with treatment-emergent adverse events (TEAEs). Secondary endpoints included change from baseline at week 12 in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) and circulating PD-1 Results: A total of 44 participants were randomized to receive JNJ-67484703 2 mg/kg ( Conclusion: JNJ-67484703 was well tolerated in participants with active RA and showed evidence for biologic and clinical activity in this small, proof-of-mechanism study. Trial registration: ClinicalTrials.gov, NCT04985812.