Axial Therapeutics has dosed the first participants in an international Phase IIb clinical trial of a gut-targeted molecular therapy, AB-2004, to treat irritability associated with autism spectrum disorder (ASD).

The double-blind, randomised, placebo-controlled study will assess the therapy to reduce irritability.

AB-2004 targets the microbiome-gut-brain axis and its role in autism.

The unique mechanism of action of AB-2004 selectivity sequesters some bacterially derived metabolites in the gut prior to their entry into the bloodstream and reaching the brain.

The first participants of the trial were administered their first AB-2004 or placebo doses at CNS Healthcare in Orlando, Florida, US; and Optimal Clinical Trials in Auckland, New Zealand, respectively.

The Phase IIb trial will assess the therapy’s tolerability, efficacy, and safety in children aged 13 to 17 years with autism and gastrointestinal symptoms.

It will recruit nearly 195 autistic adolescents at clinical trial centres in New Zealand, Australia and the US.

Axial Therapeutics CEO Stewart Campbell said: “In keeping with Axial’s mission to fundamentally improve the management of neurological conditions through our focus on the microbiome-gut-brain axis, we are truly excited to progress the clinical development of AB-2004 with the dosing of our first subjects in this double-blinded Phase IIb study.

“We are proud of our team for their continued commitment to improving the lives of children with autism and thank the investigators at our global study sites for their collaboration in successfully advancing our first-in-class, molecular therapeutic into Phase II development.”

The mean change in irritability from baseline to the eighth week for the high dose of AB-2004 will be the trial’s primary efficacy goal.

The mean change in the Clinical Global Impression-Severity from baseline to week eight for AB-2004 high and low dose, mean change in the ABC-I score (Irritability) from baseline to week eight for AB-2004 low dose will form the secondary outcome measures.

Other secondary measures include the number of subjects who report adverse events emerging from the treatment from baseline to week eight.

Furthermore, the global Phase II study is based on positive data obtained from a Phase Ib/IIa study which showed AB-2004’s favourable safety profile and improvement in irritability scores.

In 2019, Oryzon Genomics reported positive data on vafidemstat for treating aggressive behaviour of ASD patients.