National Institute for Health Research Portfolio Projects including - - PowerPoint PPT Presentation

National Institute for Health Research Portfolio Projects including Novel Drugs for Hearing

Hannah Cooper, Lecturer and Clinical Scientist (Audiology), UCL Ear Institute and Royal Berkshire NHS Foundation Trust Liz Arram, Research Audiologist, UCL Ear Institute / UCLH 5th June 2019

Develop and deliver targeted and transformative therapies for patients with deafness and hearing problems Protect - Repair - Restore

Collaborations with industry

• World class translational hearing research expertise and

infrastructure - expertise from bench to bedside

• Ultimate goal to collect

big data to build a platform informing public health policies related to hearing loss

• Strong focus on treatment of hearing loss:

– Prediction of hearing aid use and outcome – Prediction of threshold shifts after noise exposure – Prediction of cognitive decline – Hearing aids with personalised settings – Hearing aid self-management options – Prototype auditory training mobile application (based on Loo et al. 2015 Ear Hear)

Assessing hearing devices with a multi speaker test: Development of a Spatial Speech Test

• Testing word discrimination and relative

localisation simultaneously, in the presence of multi talker babble

• Q: Can this test be used to refine the hearing

aid fitting?

Assessing hearing devices with a multi speaker test

• REgeneration of inner ear hair cells with

GAmma-secretase INhibitors

• The REGAIN project aims to develop and test a

new drug administered to the ear to treat hearing loss caused by the loss of sensory hair cells in the inner ear.

Partners

Gamma Secretase Inhibitors

• Small molecule pharmaceutical drug
• Inhibits Notch, a trans-membrane receptor
• Developed for and tested systemically in

Alzheimer disease

• Repurposed for topical use in sensorineural

hearing loss

before after before after

• In adult mice with noise induced hearing loss GSI

promotes supporting cells to transdifferentiate into hair cells by blocking the Notch cell-to-cell signalling process, and partially restores hearing

Clinical Trial Progression

Trial Design

• Phase I trial – first-in-man safety study in 15

patients (UK only)

– Outcome: identification of highest safe dose

How safe is it? Phase I 15 patients

Trial Design

• Phase II trial – efficacy study in 40 patients (UK,

Greece, Germany)

– Primary outcome: hearing change at 3 months

Does it work? Phase II 40 patients

Participants inclusion criteria

 Adults (m/f, 18 - 80 years of age)  Mild to moderate bilateral sensorineural hearing loss  Hearing loss of less than 20 years duration  Using hearing aids or previously offered X Tinnitus as a primary complaint X Any significant co-morbidities

Phase I + II

• Follow Up

– Safety/Efficacy

• Local and systemic adverse events
• Changes in hearing, tinnitus – PTA, speech-in-noise, OAEs and

patient reported measures

• Changes in balance - history, examination and patient reported

measures

• Changes in facial nerve function/taste - patient reported

measures

Day 1 Day 8 Day 15

Week 1 Week 2 Week 3

Up to 28 days before treatment

Study schedule – phase I

Phase I study results

• Positive results
• Dose escalation demonstrated that trans-tympanic

injection (3 administrations, one week apart) at the highest dose of 250 micrograms was safe and well tolerated

• No safety issues were reported.

Up to 28 days before treatment

Study schedule – phase II

Phase II

• Open and recruiting
• Results anticipated in 2020