First-in-human (phase I) trial of SOL-116, a humanised IgG4 monoclonal antibody targeting bile salt-stimulated lipase, in healthy participants and rheumatoid arthritis patients.

OBJECTIVE

Bile salt-stimulated lipase (BSSL) is a digestive lipolytic enzyme and a potential novel drug target for treatment of rheumatoid arthritis (RA). Here, we report the results of the first-in-human study of SOL-116, a first-in-class humanised IgG4 monoclonal antibody targeting BSSL, conducted in healthy participants and patients with RA.

METHODS

This was a randomised, double-blind, placebo-controlled study of ascending single doses (0.075-6.075 mg/kg) and multiple doses (4 doses of 3.0 mg/kg every 4 weeks) of subcutaneously administered SOL-116 in healthy participants, as well as a single dose (2.025 mg/kg) in patients with RA. Safety and tolerability were assessed as the primary objective and pharmacokinetics (PK) and immunogenicity as secondary objectives. Exploratory objectives included evaluating BSSL concentrations and inflammatory markers.

RESULTS

SOL-116 was safe and well tolerated at the tested dose levels in 48 healthy participants and 8 patients with RA. There was a dose-proportional increase in area under the curve and maximum concentration across the single dose cohorts in healthy participants, with comparable PK characteristics between healthy participants and patients with RA and a low frequency of anti-drug antibodies. Notably, SOL-116 effectively reduced free BSSL levels in circulation, confirming target engagement although no clear changes in other exploratory inflammation markers were observed.

CONCLUSIONS

This study demonstrated that SOL-116 has a favourable safety and PK profile. Combined with effective reduction of free BSSL in the circulation, findings in this study support ongoing clinical development of SOL-116, with a focus on elucidating the efficacy and mechanism of action of BSSL in the treatment of chronic inflammation, primarily RA.

TRIAL REGISTRATION NUMBER: NCT05576012.