LY3056480 for Hearing Loss

(VESTA Trial)

Not yet recruiting at 2 trial locations

Overseen By Stephanie Moody, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Audion Therapeutics BV

Must not be taking: Ototoxic drugs

Disqualifiers: Tinnitus, Conductive hearing loss, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 2-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LY3056480, for individuals with stable sensorineural hearing loss (SNHL), a type of hearing loss caused by damage to the inner ear or the nerve pathways from the ear to the brain. The study will assess whether four injections of LY3056480, an experimental treatment, can improve hearing. Some participants will receive the actual treatment, while others will receive a placebo, a harmless, inactive substance, for comparison. Ideal candidates for this trial have had stable hearing loss for at least six months and consistent word recognition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective hearing loss therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on any therapy known to be ototoxic (harmful to the ear), you may not be eligible to participate.

Is there any evidence suggesting that LY3056480 is likely to be safe for humans?

Studies have shown that LY3056480 is generally safe and well-tolerated. In earlier research, participants received the treatment directly in their ears, and most managed it well. Researchers reported no major safety concerns. Although one study did not achieve its main goal, it confirmed the treatment's safety. Based on the available data, LY3056480 appears safe for use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hearing loss?

Unlike the standard treatments for hearing loss, which often involve hearing aids or cochlear implants, LY3056480 offers a novel approach by being directly administered transtympanically, meaning it’s delivered through the eardrum. This method allows the drug to target the inner ear more directly, potentially enhancing effectiveness. Researchers are excited about LY3056480 because it represents a fresh mechanism of action in tackling hearing loss, aiming to repair or protect delicate structures in the ear in a way that current options do not. This could pave the way for more personalized and efficient treatment strategies for individuals with hearing loss.

What evidence suggests that LY3056480 might be an effective treatment for hearing loss?

Research has shown that LY3056480 may help treat hearing loss by blocking a process called Notch signaling, which can aid in the regrowth of hair cells in the ear. These cells are crucial for hearing, and their regrowth could enhance hearing. Early trials demonstrated that LY3056480 can partly restore hearing and improve ear cell function. This trial will compare the effects of LY3056480 with a placebo to further evaluate its effectiveness, but additional research is needed to confirm these results. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-65 with stable sensorineural hearing loss (SNHL) can join this trial. They must have consistent word recognition and hearing levels for at least six months. Those with tinnitus, conductive hearing loss, genetic hearing issues, severe deafness in any frequency, or previous LY3056480 trials cannot participate.

Inclusion Criteria

Your ability to recognize and understand words has remained consistent over the past six months, with a small allowance for change.

You have had consistent hearing loss for at least six months.

You have had consistent hearing loss for at least six months.

Exclusion Criteria

I have hearing loss of more than 15 dB at one frequency or more than 10 dB across two frequencies in one ear.

I have a genetic reason for my hearing loss.

You have taken part in a previous study involving LY3056480.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four injections of 250µg LY3056480 or placebo transtympanically over 2-7 weeks

2-7 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• LY3056480

Trial Overview The trial is testing a new medication called LY3056480 to see if it helps people with stable SNHL. It's a phase 2 study which means they're looking at how effective the drug is and gathering more information on its safety.

How Is the Trial Designed?

Group I: Four injections of 250µg LY3056480 Experimental Treatment 1 Intervention

The treatment will be given transtympanically over the course of 2-7 weeks, according to dosing regimens below. * Group 1 - Regimen 1. Day 1, Day 4, Day 8, Day 11 * Group 2 - Regimen 2. Weekly * Group 3 - Regimen 3. Every two weeks

Group II: Four injections of placebo Placebo Group 1 Intervention

The treatment will be given transtympanically over the course of 2-7 weeks, according to dosing regimens below. * Group 1 - Regimen 1. Day 1, Day 4, Day 8, Day 11 * Group 2 - Regimen 2. Weekly * Group 3 - Regimen 3. Every two weeks

Who Is Running the Clinical Trial?

Audion Therapeutics BV

Lead Sponsor

Trials

1

Recruited

140+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10907343/

A phase I/IIa safety and efficacy trial of intratympanic gamma ... Our aim was to test the hypothesis that local administration with the GSI LY3056480 restores outer hair cell function and thereby improves the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38429256/

A phase I/IIa safety and efficacy trial of intratympanic gamma ... Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration.

3. ucl.ac.uk ucl.ac.uk/news/2024/mar/world-first-trial-regenerative-hearing-drug-successfully-completed

World-first trial of regenerative hearing drug is successfully ... Researchers at UCL and UCLH have successfully completed the first trial of a therapy designed to restore hearing loss.

4. regainyourhearing.eu regainyourhearing.eu/

Welcome to the REGAIN Project We report positive results from our Phase I multiple ascending dose, open-label safety study of the Notch Inhibitor LY3056480 in 15 patients with mild to ...

5. isrctn.com isrctn.com/ISRCTN59733689

ISRCTN59733689: A first-in-human study of the safety and ... LY3056480 may induce transdifferentiation of supporting cells into inner-ear hair cells and lead to a subsequent improvement of hearing in patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05061758

A Trial of LY3056480 in Patients With SNLH (VESTA) Also called a data safety and monitoring board, or DSMB. ... Safety of Several Dosing Regimens of LY3056480 in Patients With STAble Sensorineural Hearing Loss.