First Clinical Study to Evaluate Safety, Tolerability & PK of DX243 in Healthy Volunteers and Patients With Hearing Loss

This is a first-in-human, randomised, double-blind, placebo-controlled Phase 1/2a study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of DX243, a novel investigational compound, in healthy volunteers and patients with mild to moderate age-related hearing loss (ARHL). The study consists of two parts: a Phase 1 segment including single and multiple ascending dose evaluations in healthy volunteers, followed by a Phase 2a extension in patients with hearing impairment. The overall design allows for dose selection and regimen optimisation based on safety and PK results obtained in earlier cohorts.

In the Phase 2a part, 24 otherwise healthy male and female patients aged up to 75 years with up to moderately severe hearing loss will be enrolled. Patients will be randomised in a double-blind manner to receive either DX243 (two dose levels) or placebo. Treatment will consist of once-weekly subcutaneous administrations over 29 days (five injections), with 2 dosing levels selected based on Phase 1 safety, PK and modelling data to achieve target plasma concentrations while minimising local tolerability issues.

The primary objective of the Phase 2a portion is to assess the safety and tolerability of repeated subcutaneous administration of DX243, including treatment-emergent adverse events, local injection site reactions, laboratory parameters, and ECG findings. Secondary and exploratory objectives include characterisation of PK parameters and evaluation of preliminary efficacy signals using a comprehensive battery of audiological tests (including speech-in-noise performance, pure tone audiometry, and auditory brainstem response), tinnitus assessments, and quality-of-life measures. Patients will be followed for up to approximately 6 months after treatment to assess longer-term safety and durability of response.

Inclusion criteria

• Patient having self-reported recent difficulty hearing in noisy environments for at least 6 months prior to screening.
• Patient exhibiting a speech-in-noise hearing deficit in at least one ear;
• Patient having audiometrically-defined normal hearing or up to moderately severe hearing impairment

Exclusion criteria

• Current tympanic membrane perforation;
• Current acute or chronic otitis;
• Genetic hearing loss;
• Symmetric or asymmetric severe hearing loss;
• Any therapy known as ototoxic;
• Acute chronic otitis media or otitis externa terminated less than 7 days prior to randomisation;
• History of chronic inflammatory or suppurative ear disease or cholesteatoma;
• History of otosclerosis, suspected perilymph fistula or membrane rupture, suspected retro-cochlear lesion, barotrauma;
• Prior ear surgery of any kind;
• Fluctuating hearing loss;
• Patient with conductive hearing loss;
• History of Meniere's disease, autoimmune hearing loss, radiation-induced hearing loss, acoustic neuroma