Randomized Phase Ib Clinical Trial of DB-020 Intratympanic Injections to Reduce High-Dose Cisplatin Ototoxicity

Area of Science:

• Ototoxicity research
• Chemotherapy side effect management
• Pharmacology of intratympanic injections

Background:

• Cisplatin chemotherapy is associated with significant ototoxicity, leading to hearing loss.
• Protecting hearing during cisplatin treatment is a critical clinical challenge.
• Intratympanic (IT) drug delivery offers a targeted approach to the inner ear.

Purpose of the Study:

• To evaluate the safety and tolerability of DB-020, a thiosulfate formulation for intratympanic injection.
• To assess the efficacy of DB-020 in reducing cisplatin-induced ototoxicity.
• To investigate the impact of DB-020 on plasma thiosulfate concentrations.

Main Methods:

• A randomized phase Ib clinical trial involving patients receiving high-dose cisplatin chemotherapy.
• Patients received intratympanic DB-020 (12% or 25%) in one ear and placebo in the contralateral ear.
• Ototoxicity was assessed using air conduction audiometry based on American Speech-Language-Hearing Association criteria.

Main Results:

• DB-020 IT injections were safe and well-tolerated, with transient ear pain as the most common side effect.
• Ototoxicity occurred significantly less frequently in DB-020 treated ears compared to placebo ears (P = .0027).
• Incidence of ototoxicity was 85.0% in placebo ears versus 54.5% (12% DB-020) and 22.2% (25% DB-020) in treated ears.

Conclusions:

• Intratympanic DB-020 injections are a safe and tolerable method for patients undergoing cisplatin chemotherapy.
• DB-020 demonstrated a meaningful reduction in cisplatin-induced ototoxicity.
• This study supports DB-020 as a potential therapeutic agent for preventing hearing loss associated with cisplatin.