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

Abstract

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.

Keywords: Arthritis, Rheumatoid; Clinical Trial; Pharmacokinetics; Therapeutics.

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.

Keywords: Arthritis, Rheumatoid; Clinical Trial; Pharmacokinetics; Therapeutics.