Design of RESOLVE Lung, a multinational Phase 2, randomized, placebo-controlled trial of the anti-GM-CSF monoclonal antibody namilumab in patients with chronic pulmonary sarcoidosis

Abstract

Background

Pulmonary sarcoidosis is a rare inflammatory disease associated with morbidity and mortality. In light of limited treatment options, oral corticosteroids (OCS), off-label immunosuppressive therapies (IST) and tumor necrosis factor alpha inhibitors are standard of care. However, due to tolerability concerns with long-term use of OCS and IST, novel treatment options are needed. Namilumab is a potent, investigational granulocyte macrophage colony-stimulating factor humanized monoclonal antibody, that can potentially downregulate the granulomatous response, with favorable tolerability observed across clinical studies.

Study design

In this double-blind, 26-week, placebo-controlled trial, with an optional 28-week, open-label extension, approximately 100 patients will be randomized in a 1:1 ratio to receive 150 mg namilumab or placebo via subcutaneous injection. Eligible patients have active, chronic pulmonary sarcoidosis (CPS; assessed by clinical and radiologic parameters) poorly regulated by OCS and/or ISTs or failed or intolerant to treatment. At randomization, ISTs will be stopped and OCS tapered.

Objective

The objective of this trial is to evaluate the efficacy and safety of namilumab in patients with active CPS. The primary endpoint is the proportion of patients requiring rescue treatment during the double-blind period due to worsening sarcoidosis. Secondary endpoints include assessment of lung function, respiratory symptoms, and corticosteroid burden. Additionally, quality-of-life assessments, serum biomarkers, and a composite clinical benefit endpoint will be explored.

Discussion

This study will be one of the largest Phase 2 trials in the last decade for active CPS. Data from this trial will potentially provide valuable insights into disease endpoints, patient selection, and optimizing trial design.