First Clinical Study to Evaluate Safety, Tolerability & PK of DX243 in Healthy Volunteers and Patients With Hearing Loss (DX243-101)
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
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Liège
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Liège, Liège, Bélgica, 4000
- Recrutamento
- Centre hospitalier Universitaire de Liège Sart Tilman
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Contato:
- Guillaume Gersdorff, MD
- Número de telefone: +32 043232323
- E-mail: Guillaume.Gersdorff@chuliege.be
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: DX243 low flat dose
Flat dose administered sub-cutaneously for 1 month
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DX243 10 mg/mL
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Experimental: DX243 high flat dose
Flat dose administered sub-cutaneously for 1 month
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DX243 10 mg/mL
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Comparador de Placebo: Placebo
Placebo administered sub-cutaneously for 1 month
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Placebo solution, matching the external appearance of DX243.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Safety and tolerability: incidence, nature, severity and causality of treatment emergent adverse events (TEAE) and (Serious) Adverse events (S)(AEs)
Prazo: Through study completion, an average 7 months
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Through study completion, an average 7 months
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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
Prazo: For 14 days or up to normalisation after each administration whichever comes first
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For 14 days or up to normalisation after each administration whichever comes first
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Number of participants with at least one clinically significant abnormal laboratory result
Prazo: For 7 months
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Prespecified hematology, coagulation, and clinical chemistry laboratory tests will be measured in standard local laboratory units throughout the study. Each analyte will be assessed individually against the applicable reference range and for clinical significance. For this outcome measure, a patient will be counted once if he/she has at least one post-baseline abnormal clinically relevant laboratory value. |
For 7 months
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Number of Participants With Abnormal ECG Findings
Prazo: For 7 months
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Twelve-lead triplicate ECGs will be obtained at each scheduled assessment throughout the study. PR interval, QRS duration, QT interval, and QTcF interval will be measured on each of the three ECG tracings. Overall ECG interpretation (normal/abnormal) and clinical significance of any abnormality will be determined by the investigator or qualified reader based on review of the triplicate ECG assessment. For this outcome measure, a participant will be counted once if at least one post-baseline ECG assessment is abnormal. |
For 7 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in Pure Tone Audiometry
Prazo: For 7 months
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For 7 months
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Change in speech audiometry
Prazo: For 7 months
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For 7 months
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Hearing Handicap Inventory for the Elderly- Screening (HHIE-S) questionnaire score
Prazo: For 7 months
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0 to 8 = 13% probability of hearing impairment (no handicap/no referal) 10 to 24= 50% probability of hearing impairment (mild-moderate handicap/refer) 26 to 40=84% probability of hearing impairment (severe handicap/refer)
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For 7 months
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Severity of tinnitus
Prazo: For 7 months
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Tinnitus assessment (acouphenometry) and Tinnitus Functional Index (TFI)
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For 7 months
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Distorsion Product OtoAcoustic Emission (DPOAE)
Prazo: For 7 months
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For 7 months
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Quality of Life (QoL) assessed using 15iSSQ scale
Prazo: For 7 months
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The 15-item Speech, Spatial, and Qualities of Hearing Scale is a 15-item questionnaire that evaluates hearing-related quality of life.
It measures self-reported abilities in three specific hearing domains: Speech, Spatial, and Qualities of hearing.
Higher scores indicate better hearing performance and fewer limitations in daily life.
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For 7 months
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- DX243-101
- 2023-505778-14-00 (Ctis)
Plano para dados de participantes individuais (IPD)
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