Safety and immunogenicity of PPV-06, an active anti-IL-6 immunotherapy targeting low-grade inflammation against knee osteoarthritis: a randomized, double-blind, placebo-controlled, clinical phase 1 study

Abstract

Osteoarthritis, a debilitating joint disorder, remains a major unmet medical need requiring new treatment options. Here, we evaluate the safety (primary endpoint) and immunogenicity (secondary endpoint) of PPV-06, an active anti-IL-6 immunotherapy designed to mitigate the impact of low-grade inflammation on disease progression. Twenty-four participants affected by inflammatory knee osteoarthritis (KOA) are enrolled in a randomized, placebo-controlled phase 1 clinical trial (NCT04447898) and divided into three groups, receiving low (10 µg, n = 9), high (50 µg, n = 9) dose of PPV-06, or placebo (n = 6). We observe a good safety profile with no dose-limiting toxicities in either the PPV-06 or the placebo groups. The incidence of adverse events is similar across the three groups, with mild to moderate drug-related adverse events typically associated with vaccines, including injection-site induration, pruritus, erythema, and headache. All participants receiving PPV-06 exhibit anti-IL-6 antibodies, and interestingly, participants with higher IL-6 neutralizing capacity exhibit an improved clinical outcome, as determined by changes in KOOS scores. These findings support further development of PPV-06 as a promising therapeutic strategy for knee osteoarthritis.