Scientific title

A Phase I/II multiple ascending dose open-label safety and efficacy study of the Notch Inhibitor LY3056480 in patients with mild to moderate SNHL

Acronym

REGAIN

Study hypothesis

LY3056480 may induce transdifferentiation of supporting cells into inner-ear hair cells and lead to a subsequent improvement of hearing in patients with sensorineural hearing loss (SNHL).

Ethics approval

London - Central REC Committee, 25/10/2017, ref: 17/LO/0632

Study design

Part 1: Open-label single centre multiple ascending dose safety study

Part 2: Multi-centre efficacy randomised study

Primary study design

Interventional

Secondary study design

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Sensorineural hearing loss

Intervention

In the first part of this study, participants have three treatment visits where they receive three injections of LY3056480 administered trans-tympanically into one ear. This is done using a location anaesthetic cream to numb the ear drum. The drug is injected through the eardrum using a syringe. This injection takes approximately ten minutes. This is done in ascending dose cohort of 25μg, 125μg, 200μg, and 250μg applied in 500 μl. The maximum dose is determined by the maximum volume that can be administered in the inner ear and the maximum solubility in the formulation. For the selected starting dose a safety factor of ten is applied, starting with 10% of the maximum dose. Participants are asked to lay till with their head in a set position for one hour after receiving their injections.



At the first visit, participants receive a dosage of 25μg and stay overnight at the hospital in order to monitor their hearing, balance, and general health to assess the safety of the drug. Participants are monitored routinely for their blood pressure, heart rate, and oral temperature. After participants are assessed for their hearing, balance and general health they are discharged. Participants then receive a telephone call the day after the first study visit to check how they are feeling. Six days after the first treatment visit, participants return to the hospital to repeat the tests.



The second visit occurs seven days after the first visit. Participants return to the hospital and the injection is repeated (25μg). Participants are able to go home after they are assessed for hearing balance and general health. Participants receive a telephone call one day after treatment to see how they are feeling. Participants then return to the hospital six days after their second visit for a safety visit, which repeats some of the assessments.



The third study visit occurs seven days after the second study visit. Participants return to the hospital and the injection is repeated (25μg). Participants are able to go home after they are assessed for hearing balance and general health. Participants receive a telephone call one day after treatment to see how they are feeling. Participants then return to the hospital six days after their second visit for a safety visit, which repeats some of the assessments.



Participants receive two more follow up visits, six and 12 weeks after their first treatment visit. The follow up takes around half a day and assesses the safety of the new drug. The overall study takes around 14 weeks.



In the second phase of the study, participants receive the highest tolerable dose resulted from the first section of the study or one dose below the highest tolerable dose (if the Maximum Tolerated Dose MTD is reached in the first part of the study). This part is designed to establish efficacy parameters at the MTD but also allows us to possibly determine a potential dose-response effect. If the MTD is found, participants are randomly assigned to the MTD or the dose below the MTD. Injections are delivered in the same process as the first part of the study.

Intervention type

Drug

Phase

Phase I/II

Drug names

LY3056480

Primary outcome measure

Part 1:

1. Occurrence and severity of procedure related local and systemic AEs are measured using clinical examinations, laboratory tests and patient interviews at visit one, two and three

2. Occurrence of systemic AEs as measured by potentially clinically significant changes by ECG, vital signs, physical examinations and laboratory tests at visit one, two and three

3. Occurrence of surgical and injection sites reactions in and around the treated ear as assessed by otomicroscopy at visit one, two and three

4. Safety of the treatment is assessed using changes in hearing, facial nerve function and balance at visit one, two and three



Part 2:

Efficacy of local treatment is measured if an optimal dose is found in part 1.

Secondary outcome measures

1. Change in hearing is measured using Pure Tone Audiometry (PTA) (dBHL) at baseline and week 12

2. Balance is measured using several balance tests at visit one, two, and three

3. Tinnitus measured using a questionnaire at visit one, two and three



Overall trial start date

01/07/2016

Overall trial end date

31/12/2019

Reason abandoned (if study stopped)