A Phase 2a clinical study to evaluate the safety and efficacy of CS-1103, a therapeutic agent to treat methamphetamine intoxication

About This Grant

PROJECT SUMMARY There is an urgent need for a rapidly acting antidote for methamphetamine. Methamphetamine (Meth) is the fastest growing drug of abuse in the U.S., representing over 547,000 annual emergency department (ED) visits, with deaths increasing 14-fold since 2015 (32,856 deaths in 2021 alone), costing the U.S. hospital system over $8B per year, yet no FDA approved therapeutics are available to treat meth intoxication. A study of 1.29M Meth-related hospitalizations showed a 29% higher in-hospital mortality compared to other admissions. CS-1103 represents a breakthrough in the treatment of methamphetamine intoxication, offering a dual mechanism of action: (1) rapid reversal of acute toxidrome symptoms, and (2) elimination of the underlying cause by accelerating Meth clearance from the body. CS-1103 reverses meth intoxication by sequestering Meth in the plasma compartment and removing it from the central nervous system effect site. The now ‘inactive’ Meth is eliminated from the body into urine by filtration in the kidney. Rapid sequestration and clearance of Meth rapidly reverses its effects. CS-1103 is indicated to treat patients with known or suspected Meth intoxication. Under NIDA support, we (1) successfully opened an IND (155105) and completed all nonclinical studies requested by FDA; (2) established Current Good Manufacturing Practice (cGMP) processes for drug substance (DS) and drug product (DP); (3) demonstrated that CS-1103 administered via intravenous (IV) injection has a favorable safety and tolerability profile in a Phase 1 first-in-human clinical trial (NCT06316973) up to the maximum dose evaluated, 17.9 mg/kg, and confirmed the PK profile of CS-1103; (4) demonstrated in non-human primate (NHP) that CS-1103 was highly effective in lowering the level of Meth and rapidly reversing its toxic effects. In a canine study at a 2:1 CS-1103:Meth molar ratio, CS-1103 protected against a Meth dose 11-fold higher than LD50. In rat, CS-1103 significantly accelerated renal excretion even when administered hours after Meth, and completely prevented cardiac damage. Thus CS-1103 not only provides rapid reversal of symptoms, but also prevents further organ damage. We are in active discussions with FDA and are ready to recruit and admit participants into the Phase 2a study (NCT06721494) proposed here, described in the following Specific Aim. Aim 1 will determine dosing requirements for CS-1103 in a Phase 2a clinical trial. The Phase 2a trial is a randomized, double-blinded, placebo-controlled, dose escalation study clinical study to evaluate efficacy and dose-response of CS-1103. Single IV doses of CS-1103 will be administered after an IV dose of Meth in 40 individuals with Meth use disorder not seeking treatment. The objectives of the study are to: assess the safety, tolerability and PK of CS-1103 following Meth exposure; establish the dose-response relationship of CS-1103 by quantifying Meth levels in plasma and urine; evaluate the efficacy of CS-1103 in reversing Meth-induced behavior and cardiovascular changes. The expected outcome is CS-1103 optimal dose.