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

Официальное название

Double-blind, Randomised, Placebo-controlled Phase 1/2a Study of Safety, Tolerability and PK of Single and Repeated SC Doses of DX243 in Healthy Volunteers, and 1-month Safety and Efficacy in Moderately Severe Age-related Hearing Loss

Обзор

Phase 2a: Multiple Ascending Dose (MAD) in male and female patients with hearing loss: The study will be conducted according to a randomised, placebo-controlled, double-blind design. A total of 24 patients, otherwise healthy, aged up to 75 years old, with mild to moderate hearing loss will be included. Two cohorts of 12 male or female patients (no ratio is required) will receive two different flat doses (low dose and high dose) ofDX243 or placebo for 29 days using SC administration. In each cohort of 12 patients, 4 will be randomised to placebo and 8 to DX243, so at the end of Phase 2a, 8 patients will have received placebo, 8 the low dose and 8 the high dose of DX243. The primary objective is to evaluate the safety and tolerability of DX243 administered subcutaneously after repeated doses. The secondary objectives are to detect preliminary signal of efficacy, using speech in noise tests, tonal and vocal audiometry, as well as tinnitus and quality of life.

Подробное описание

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.

Вмешательства

• Препарат DX243
  DX243 10 mg/mL
• Препарат Placebo
  Placebo solution, matching the external appearance of DX243.

Первичные конечные точки

• Safety and tolerability: incidence, nature, severity and causality of treatment emergent adverse events (TEAE) and (Serious) Adverse events (S)(AEs) [Срок оценки: Through study completion, an average 7 months]
• Tolerability at the injection sites using a 1-5 scale Common Terminology Criteria for Adverse Events (CTCAE) for pain, erythema, swelling, induration, nodule and ulceration with 1 : normal and 5: worst possible symptom/sign [Срок оценки: For 14 days or up to normalisation after each administration whichever comes first]
• Number of participants with at least one clinically significant abnormal laboratory result [Срок оценки: For 7 months]
• Number of Participants With Abnormal ECG Findings [Срок оценки: For 7 months]

Вторичные конечные точки (6)

• Change in Pure Tone Audiometry [Срок оценки: For 7 months]
• Change in speech audiometry [Срок оценки: For 7 months]
• Hearing Handicap Inventory for the Elderly- Screening (HHIE-S) questionnaire score [Срок оценки: For 7 months]
• Severity of tinnitus [Срок оценки: For 7 months]
• Distorsion Product OtoAcoustic Emission (DPOAE) [Срок оценки: For 7 months]
• Quality of Life (QoL) assessed using 15iSSQ scale [Срок оценки: For 7 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Бельгия · 1 центр

• Centre hospitalier Universitaire de Liège Sart Tilman — Liège

Идентификаторы

NCT: NCT07637981 · DX243-101 · 2023-505778-14-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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