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

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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-11-05
DOI
https://doi.org/10.1038/s41467-025-64710-6
Citations
1
Primary Topic
Osteoarthritis Treatment and Mechanisms
Type
article
Field-Weighted Citation Impact
1.67
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Quentin Kirren, Jean‐Pierre Salles, Marie‐Christophe Boissier, Christelle Nguyen et al.
1 citations
Nature Communications
Osteoarthritis Treatment and Mechanisms
1.67
article

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

Quentin Kirren, Jean‐Pierre Salles, Marie‐Christophe Boissier, Christelle Nguyen, Camille Daste, Florent Langenfeld, Lucille Desallais, Edita Dolimier, Barbara Ruiz, Odile Launay, Gabriel Moreau, Hadley Mouhsine, Marie‐Martine Lefèvre‐Colau, Francis Bérenbaum, René Azoulai, François Rannou, Jean-François Zagury, Hervé Do
article en
1 citations

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.

Nature CommunicationsVol. 16(1)
Conservatoire National des Arts et Métiers (FR), Inserm (FR), Université Paris Cité (FR), Sorbonne Université (FR), Université Sorbonne Paris Nord (FR), Sorbonne Paris Cité (FR), Hôpital Cochin (FR), Assistance Publique – Hôpitaux de Paris (FR), Clinical Investigation Center Plurithematic Tours (FR), Toxicologie, Pharmacologie et Signalisation Cellulaire (FR), Génomique Bioinformatique et Applications (FR), Hôpital Avicenne (FR), Centre de Recherche Saint-Antoine (FR), Association Française pour le Dépistage et la Prévention des Handicaps de l’Enfant (FR), Centre de Recherche Épidémiologie et Statistique (FR)
Openalex Percentile: Top 12%
Osteoarthritis Treatment and Mechanisms
1.67
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.