A study of OTO-313 given as an injection in patients with tinnitus
Research type
Research Study
Full title
A randomized, double-blind, placebo-controlled phase 2 study of OTO-313 given as a single intratympanic injection in subjects with unilateral subjective tinnitus
IRAS ID
1003768
Contact name
Minal Kara
Contact email
Sponsor organisation
Otonomy Inc
Eudract number
2021-000229-28
Clinicaltrials.gov Identifier
Research summary
Research Summary
Unilateral tinnitus is the perception of noise or ringing in one ear without any outside source causing the sound. Tinnitus can be distressful and impact a patient’s quality of life. There is no cure for tinnitus, but patients may manage their symptoms with counselling, use of hearing aids, sound-based therapy or cognitive behaviour therapy.
The purpose of this study is to test the safety and effectiveness of the investigational product, OTO-313, compared to placebo (looks like OTO-313 but with no active ingredient) in people with early-onset, unilateral tinnitus. OTO-313 or placebo will be given once by injection through the ear drum. Injecting the investigational product through the ear drum places it close to the part of the ear that may be the cause of the tinnitus. This is considered a more local delivery. The OTO-313 dose and placebo to be used in this study have been used in an earlier study in unilateral tinnitus. In that study both the injection and the investigational product were well-tolerated
The study will last about 20 weeks with about 6 visits.
This is a double-blind study, which means neither the participant nor the study staff will know if a participant receives OTO-313 or placebo.
Otonomy, Inc., is sponsoring this multicentre study with approximately 140 participants globally.Summary of Results
Description: A study comparing local application in one ear of gacyclidine (a research compound) to placebo in people with tinnitus (ringing or noise in the ear) to see if it could reduce the severity of their tinnitus symptoms and if it is safe to use. The study was sponsored by Otonomy, Inc. www.otonomy.com.
General Information: The purpose of this trial was to test the effectiveness (how well it works) and safety of an investigational drug, OTO-313, compared to placebo in people with unilateral subjective tinnitus (ringing or noise in one ear when there is no noise or ringing being made). This trial focused on how tinnitus affected people before receiving the treatment and after, using the Tinnitus Functional Index questionnaire (TFI) that the subject would complete at every trial visit. There were 56 clinical sites approved for this study and the enrolment per country was: Germany (13), Poland (25), US (114), and UK (1). The first subject enrolled on 7Apr21 and the last subject completed on 14Jun22.
Trial Design: The trial was randomized, placebo-controlled and double-blind with 2 treatment groups (OTO-313 and placebo). The trial used a placebo control, which the Sponsor believed was the most direct way to measure the effect of OTO-313.
There was a 2-week lead-in period before a subject could be randomized to receive a one-time injection in their ear of either OTO-313 or placebo (Baseline visit). Subjects recorded tinnitus loudness and annoyance using a smart phone app every night and returned to the study site at 4, 8, 12, & 16 Weeks. At all visits, staff examined the subject to check safety and tinnitus symptom severity.
Trial Participants: 153 people were randomized in this trial. 77 people received OTO-313 and 74 received placebo. 2 people randomized to receive placebo left the study before they received it. 142 people completed the study and 11 discontinued the study early. Of these 11, 5 people in the OTO-313 group and 3 in the placebo group withdrew their consent to be in the study (includes the 2 untreated people already mentioned) and 2 people in the OTO-313 group and 1 in the placebo group were considered “lost to follow-up”.
There were 36 males (46.8%) and 41 females (53.2) in the OTO-313 group and 38 males (50.0%) and 38 females (50.0%) in the placebo group. People in the study ranged from 19 to 75 years old. The average age of the study subjects was 51 years. Most people in the study identified their race as White (88%) and ethnicity as not Hispanic (88%).
Trial Drugs: People in this study received a single 0.2 millilitre injection (approx 4 drops) of OTO-313 or placebo through the ear drum of one ear (an intratympanic or IT injection). The ear drum was numbed before the injection and the subject had to lie with the injected ear facing up for 15 min after the injection.
OTO-313 is a solution of the investigational compound gacyclidine in medium chain triglycerides (MCT), an oil commonly used in pharmaceutical preparations. The placebo used in this trial was plain MCT.
Safety Results: The key safety measure was how many adverse events (AE) were reported by people that received OTO-313 or placebo. An AE is defined as unfavourable symptom that occurred during the study and was absent prior to the ear injection. Most of the reported AEs were associated with the ear (tinnitus and vertigo) or with an infection (COVID-19, common cold, urinary tract infection) and occurred at a similar rate between the 2 groups.
There were no changes in vital signs (pulse, blood pressure), clinical laboratory measures, or hearing in both groups. Overall, OTO-313 was safe in this trial.
Efficacy Results: The main reason for this study was to see if OTO-313 reduced tinnitus symptoms by seeing the percentage of responders, i.e., a person that had a TFI score of at least 13 points less at the visits after getting the injection). There were responders in both groups with more at Week 4 in placebo and very slightly more at Weeks 8, 12, and 16 in OTO-313. Since the difference between the 2 groups was small, the conclusion was that OTO-313 did not have a meaningful effect on reducing the impact of tinnitus.
People scored the level of loudness and annoyance of their tinnitus every day by filling in a 10-point scale in an app on their smart phone. People in both groups rated the loudness and annoyance of their tinnitus less and less as the study went on, but the difference between the two groups was very small and both treatment groups seemed to get better at the same rate. This slight difference was not enough to conclude that OTO-313 was more effective in reducing tinnitus loudness or annoyance. Overall, OTO-313 was not shown to be effective in this trial.
Follow-up Clinical Trials - The Sponsor has no plans to conduct additional clinical trials with OTO-313 in people with tinnitus. More information on results will be posted on https://clinicaltrials.gov/show/NCT04829214 and Eudract.REC name
London - Surrey Borders Research Ethics Committee
REC reference
21/LO/0394
Date of REC Opinion
4 Jul 2021
REC opinion
Further Information Favourable Opinion