A first-in-human study of the novel immunology antibody-drug conjugate, ABBV-3373, in healthy participants.

Aims: ABBV-3373, an immunology antibody-drug conjugate composed of adalimumab conjugated to a proprietary glucocorticoid receptor modulator (the small-molecule payload), has the potential to treat immune-mediated inflammatory diseases. This first-in-human study investigated the pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) using a safety PD marker, and safety/tolerability of ABBV-3373 in healthy adults.

Methods: Fifty-five participants were randomly assigned to single-dose subcutaneous (SC; 30, 100 or 300 mg) or intravenous (IV; 30, 300 or 900 mg) ABBV-3373 or placebo. Eight additional participants received a single dose of 10 mg oral prednisone for evaluation of systemic glucocorticoid effects. Blood samples were collected for up to 85 days postdose for PK, anti-drug antibody and serum cortisol (safety PD marker) assessments.

Results: ABBV-3373 and total antibody displayed antibody-like SC/IV PK profiles and the unconjugated/free payload in circulation exhibited formation rate-limited kinetics with exposure several fold lower than ABBV-3373 or total antibody. Treatment-emergent anti-drug antibody incidence was 69%, with loss of exposure in 6% (SC) and 5% (IV) of participants, but without any impact on safety. ABBV-3373 up to 300 mg SC/IV had no apparent impact on serum cortisol, and only caused a transient decrease at 900 mg IV. Treatment-emergent adverse events were primarily mild in severity, and no pattern emerged with respect to dose or route of administration.

Conclusions: ABBV-3373 had favourable PK profiles, manageable immunogenicity, and was generally well-tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV-3373.