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.
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
Current tympanic membrane perforation;
Current acute or chronic otitis;
Genetic hearing loss;
Symmetric or asymmetric severe hearing loss;
Parallel
DX243
DrugDX243 10 mg/mL
Placebo
DrugPlacebo solution, matching the external appearance of DX243.
Safety and tolerability: incidence, nature, severity and causality of treatment emergent adverse events (TEAE) and (Serious) Adverse events (S)(AEs)
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
Number of participants with at least one clinically significant abnormal laboratory result
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.
Number of Participants With Abnormal ECG Findings
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.
Change in Pure Tone Audiometry
Change in speech audiometry
Hearing Handicap Inventory for the Elderly- Screening (HHIE-S) questionnaire score
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)
Severity of tinnitus
Tinnitus assessment (acouphenometry) and Tinnitus Functional Index (TFI)
Click on the lead sponsor to view all of their trials.
