Journal Article

Safety, pharmacokinetics, and pharmacodynamics of MK-6194, an IL-2 mutein designed to selectively activate regulatory T cells: single ascending dose and multiple ascending dose trial data

Kis-Toth, Katalin, Iwamoto, Marian, Baltus, Gretchen A, Sicard, Eric, Robbins, Jonathan A, Scheid, Johannes F, Decaesteker, Tatjana, Franco-Dilone, Lucia, Viney, Joanne L, Sutradhar, Santosh, Paul, Erina, Mendez, Luis, Contreras, Alejandra Virginia, Pang, Ling, Sundy, John S, Otipoby, Kevin L, Cunningham-Bussel, Kiki, Love-Gregory, Latisha, Higginson-Scott, Nathan, Larson, Patrick, Nieddu, Garrett, Agarwal, Shiuli, Stoch, S Aubrey, Van Dyck, Kristien, Wnek, Richard, Laethem, Tine, Lai, Eseng, Bueters, Tjerk, Beaumont, Maribel, Lemoine, Lieselotte, Rottey, Sylvie, Kim, Nancy, Shah, Ketal, Zhao, Xuemei, Cote, Josee

2025

Overview

MK-6194, an interleukin-2 mutein designed to selectively activate regulatory T cells (Tregs), was evaluated for safety, pharmacokinetics (PK), immunogenicity, and pharmacodynamics in healthy participants. In a single ascending dose trial (N = 56), participants received subcutaneous MK-6194 or placebo (3:1 ratio) across dose levels ranging from 1 to 10 mg. In a multiple ascending dose trial (N = 54), participants received subcutaneous MK-6194 or placebo (3:1 ratio) at dose levels ranging from 0.5 to 5 mg every 2 wk (total 3 doses) as well as 5 mg every 4 wk (total 2 doses). Baseline characteristics were comparable between trials, with participants mostly male with a mean age of 36 yr. There were no serious adverse events or dose-limiting toxicities. The most common adverse events were injection site erythema and eosinophil count elevations (with no indication of severe eosinophilia or eosinophilia-related organ damage). PK showed dose-proportionality and repeated doses of MK-6194 did not result in accumulation or time-dependent PK. Immunogenicity was low with no impact on PK or safety. Treg expansion as assessed by flow cytometry and Treg-specific demethylation region analysis was observed in a dose-dependent manner during both trials and expanded within about 8 d postdose up to about 5-fold and returned to baseline by 14 to 29 d postdose. Minimal impact was observed on other lymphocytes including total T lymphocyte and natural killer cell counts. These findings support the further development of MK-6194 as a potential treatment for autoimmune disorders.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / Dose-Response Relationship, Drug / Double-Blind Method / Female / Healthy Volunteers / Humans / Interleukin-2 - administration & dosage / Interleukin-2 - adverse effects / Interleukin-2 - analogs & derivatives / Interleukin-2 - pharmacokinetics / Male / Middle Aged / Recombinant Proteins / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / Young Adult