Alto Neuroscience has commenced a Phase II clinical trial of histamine H3 receptor inverse agonist, ALTO-203, in treating patients with major depressive disorder (MDD).

The double-blind, single-dose and multiple-dose study will assess the pharmacodynamics, safety, tolerability, and pharmacokinetics of two doses of the ALTO-203 monotherapy versus placebo.

This trial is structured into two sequential double-blind, placebo-controlled treatment periods.

The initial phase will employ a randomised, single-dose treatment design, focusing on the pharmacodynamic responses of the trial subjects to ALTO-203 versus placebo.

An acute change in positive emotion evaluated using the Bond-Lader Visual Analog Scale (BL-VAS), a recognised scale for subjective feelings, will be the trial’s primary outcome.

Following the single-dose period, a 28-day multi-dose exposure phase will commence to further analyse the safety profile of the therapy in MDD patients.

This second part of the study will also explore changes in depression severity, anhedonia, and other clinical symptoms, as well as cognitive functions.

Approximately 60 adult MDD patients with evidence of anhedonia will be enrolled in the trial.

The company anticipates reporting topline data from this study in the first half of next year.

Alto Neuroscience chief development officer Jessica Powell said: “This is the fifth Phase II study we have initiated across our pipeline, a milestone that marks significant progress in our efforts to redefine mental healthcare through our Precision Psychiatry Platform.

“In a Phase I study, ALTO-203 demonstrated an acute increase in positive emotion relative to placebo and across several dosage levels. We look forward to completing this proof-of-concept study in patients as we believe this response may be an important attribute of an antidepressant to benefit patients with MDD and higher levels of anhedonia specifically.”

Last November, the company secured $45m in a Series C financing round.