Safety and efficacy of namilumab for the treatment of chronic pulmonary sarcoidosis (RESOLVE-Lung): a randomised, double-blinded, multicentre, phase 2 study.

BACKGROUND

Treatment options for chronic pulmonary sarcoidosis are limited in efficacy and by tolerability concerns. Namilumab, an investigational humanised monoclonal antibody inhibiting granulocyte-macrophage colony-stimulating factor, was hypothesised to downregulate the granulomatous response in pulmonary sarcoidosis.

METHODS

RESOLVE-Lung was a double-blind, placebo-controlled trial in participants with chronic active pulmonary sarcoidosis on oral corticosteroids (OCS) and/or immunosuppressive therapies (IST). Participants were randomised (1:1) to receive 150 mg namilumab or placebo via subcutaneous injection every 4 weeks and were required to stop IST and/or taper OCS. End-points were assessed at week 26. The primary end-point was the proportion of participants with a rescue event, such as disease worsening necessitating treatment. Secondary end-points included safety, lung function assessments and corticosteroid burden. The trial was registered at ClinicalTrials.gov (NCT05314517).

RESULTS

Of 209 participants screened, 107 were randomised to receive namilumab (n=53) or placebo (n=54). The proportion of participants with a rescue event was higher for the namilumab group (37.5%) compared with the placebo group (23.5%) (stratified difference 13.6 (90% CI -1.5-28.7) percentage points; p=0.12). The least squares (LS) mean change from baseline in forced vital capacity % predicted was -3.3 (90% CI -5.1- -1.5) percentage points for namilumab and -2.9 (90% CI -4.5- -1.3) percentage points for placebo (LS mean difference -0.4 (90% CI -2.7-2.0) percentage points). The proportion of participants successfully achieving OCS taper was 53.3% for namilumab and 76.9% for placebo (difference -19.4 (90% CI -47.5-8.7) percentage points). Treatment-emergent adverse events were reported in 94% in both groups, most being mild or moderate in severity.

CONCLUSION

In participants with chronic active pulmonary sarcoidosis, namilumab did not provide clinical benefit.