MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose)

  • Clin Transl Sci. 2023 Nov;16(11):2236-2252. doi: 10.1111/cts.13623.
Baltazar Gomez-Mancilla  1  2 ,  Jeffrey A Levy  3 ,  Subramanian Ganesan  4 ,  Thomas Faller  1 ,  Gil Issachar  5 ,  Ziv Peremen  5 ,  Offir Laufer  5 ,  Revital Shani-Hershkovich  5 ,  Kostas Biliouris  6 ,  Ela Walker  1 ,  Mark P Healy  6 ,  Oleksandr Sverdlov  7 ,  Sachin Desai  7 ,  S Nassir Ghaemi  6  8 ,  Jang-Ho Cha  6 ,  Y Gopi Shanker  6  9
Affiliations
  • 1. Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
  • 2. McGill University, Montreal, Québec, Canada.
  • 3. Seaview A Quotient, Miami, Florida, USA.
  • 4. Novartis Healthcare Pvt. Ltd., Hyderabad, India.
  • 5. Elminda Ltd., Herzliya, Israel.
  • 6. Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • 7. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
  • 8. Tufts Medical Center, Tufts University, Boston, Massachusetts, USA.
  • 9. Beam Therapeutics, Cambridge, Massachusetts, USA.
PMID: 37817426 DOI: 10.1111/cts.13623
Abstract

This single-center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40-min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUCinf values of MIJ821 increased in a dose-proportional manner across the dose range 0.016-0.48 mg/kg and the Cmax values in a slight overproportional manner across the dose range 0.048-0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUCinf was 708 h ng/mL and the geometric mean Cmax was 462 ng/mL. Inspection of 1-h post-dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose-dependent.

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