First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor.

Area of Science:

• Immunology
• Pharmacology
• Clinical Trials

Background:

• The classical complement system plays a role in various diseases.
• Activated C1s is a key component in the proximal classical complement pathway.
• Targeting C1s offers potential therapeutic benefits for complement-mediated disorders.

Purpose of the Study:

• To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SAR445088 in healthy participants.
• To assess SAR445088 following single ascending doses (SAD) via intravenous (i.v.) and subcutaneous (s.c.) routes.
• To assess SAR445088 following multiple subcutaneous (s.c.) ascending doses (MAD).

Main Methods:

• A Phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial.
• Involved 93 healthy participants receiving single and multiple doses of SAR445088.
• Pharmacodynamic assessments included Wieslab CP and complement mediated hemolytic capacity (CH50) assays.

Main Results:

• SAR445088 was well-tolerated across all tested doses and administration routes (i.v. and s.c.).
• Pharmacokinetics demonstrated slow absorption with s.c. dosing and a long terminal half-life (8-15 weeks).
• Pharmacodynamic assays indicated effective inhibition of the classical complement pathway with determined IC50 and IC90 values.

Conclusions:

• SAR445088 exhibits a favorable safety, tolerability, PK, and PD profile in healthy humans.
• The observed profiles support further clinical investigation of SAR445088 in patients with complement-mediated diseases.
• These findings suggest SAR445088's potential as a therapeutic agent for classical complement pathway-driven conditions.