Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss (CLARITY-1)

• ClinicalTrials.gov Identifier: NCT02345031
• Recruitment Status: Completed
• First Posted: January 26, 2015
• Results First Posted: September 19, 2017
• Last Update Posted: August 9, 2018
• Sponsor: Autifony Therapeutics Limited
• Information provided by (Responsible Party): Autifony Therapeutics Limited

Study Description

Brief Summary:

This study aims to demonstrate that the investigational drug AUT00063 is effective and safe in the treatment of age-related hearing loss.

Condition or disease	Intervention/treatment	Phase
Age-Related Hearing Loss	Drug: AUT00063; Drug: Placebo	Phase 2

Detailed Description:

Reduced activity at certain sites in the brain (called "voltage-gated potassium channels") has been linked to hearing problems, like age-related loss of hearing or tinnitus (a 'ringing' or buzzing noise in the ears).

AUT00063 is an experimental new medicine that enhances the action of these specific channels and so may treat the brain component of these hearing problems.

The main purpose of this study is to try to demonstrate an improvement in a speech-in-noise deficit after 4 weeks of treatment with the study drug versus the placebo (dummy drug which does not contain the drug). Subjects will undergo a safety follow-up after the treatment period.

Safety and efficacy will be determined by looking at a number of assessments (physical examinations, blood sampling, hearing assessments, questionnaires, etc.).

The amount of drug in the blood will also be measured. It is expected that around 70 people (at least 35 in each arm) with age-related hearing loss may take part in the study. The study participants will be recruited at around 13 sites in the USA.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Balanced, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss [CLARITY-1 Study]
• Study Start Date: January 2015
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AUT00063 (600 mg capsules); 3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks	Drug: AUT00063; 600 mg, orally, once a day, for 4 weeks; Other Name: Experimental
Placebo Comparator: (AUT00063 placebo capsules); 3 capsules of placebo, to take orally once daily with food for 4 weeks	Drug: Placebo; orally, once a day, for 4 weeks; Other Name: Comparator

Outcome Measures

Primary Outcome Measures :

1. Change in Hearing Loss After 4 Weeks of Treatment [ Time Frame: 28 days ]
   To compare the change in hearing using the QuickSIN test (speech in noise performance) from baseline (Day 1 to Day 28) between AUT00063 and placebo. The QuickSIN test measures the level of signal compared to the noise that is required to achieve 50% recognition. The test is administered in a sound booth at 70-dB HL binaurally via insert-ear phones. Three lists are administered to each individual subject and the threshold or 50% signal-to-noise ratio (SNR) is calculated as the mean of the three lists completed. Each list consists of six sentences with five key words to be scored per sentence. The sentences are presented in four-talker babble noise. The sentences are presented at pre-recorded signal-to-noise ratios which decrease in 5-dB steps from 25 (very easy) to 0 (extremely difficult).

Secondary Outcome Measures :

1. Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28 [ Time Frame: 28 days ]
   Final Average GDT Across-Channel at Day 28: Change from Baseline; FAS Population
2. Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28 [ Time Frame: 28 days ]
   Final Average GDT Within-Channel at Day 28: Change from Baseline; FAS Population
3. To Further Investigate the Safety and Tolerability Profile of Repeat Administration of AUT00063 by Assessing Vital Signs, Physical Examination, Laboratory Exams and ECG [ Time Frame: 42 Days ]
   Number of Subjects With At Least One Treatment Emergent Adverse Event
4. Pharmacokinetic of AUT00063, Plasma Levels [ Time Frame: 28 Days ]
   Exposure of AUT00063 ng/ml, in plasma levels at Day 28

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• Be between ages 50-89 years old
• American-English speaking
• Have difficulty hearing speech in a noisy environment
• No recent history of middle ear disease
• No severe insomnia, major depressive disorders, severe anxiety or post-traumatic stress disorder
• Not a current or previous user of hearing aids. You are eligible if you were noncompliant and stopped wearing a hearing aid device >6 months earlier for intermittent use or >3 years if you were a full-time consistent user of hearing aid devices
• Not be dependent on alcohol or drugs
• Have not participated in another research study within 30-days
• If female, you must confirm to be non child bearing (post-menopausal for at least 12-months or surgically sterile)
• If male, you must confirm to use a barrier method (condom)
• Not be a professional musician
• No history of important cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major disease deemed clinically significant by the study doctor

While you are in the study, you must:

• Follow the instructions you are given
• Come to the study centre for all visits with the study doctor or study staff
• Answer the telephone at the scheduled date and time for the 2 telephone calls
• Tell the study doctor or study staff about any changes in your health or the way you feel
• Tell the study doctor or study staff if you want to stop being in the study at any time
• Bring your Diary to each visit
• Not eat or drink anything containing Grapefruit beginning 7-days before Baseline visit (Visit 3, Day 1) until the end of the study
• Use sun screen if you plan to sunbathe
• Not use headphones or headsets at high volume
• Not use hearing aids or devices at any time during the study

Contacts and Locations

Locations

United States, California

Sacramento ENT

Sacramento, California, United States, 95815

United States, Colorado

Colorado ENT and Allergy

Colorado Springs, Colorado, United States, 80909

United States, Florida

ENT Associates of South Florida

Boca Raton, Florida, United States, 33487

QPS MRA (Miami Research Associates)

Miami, Florida, United States, 33143

University of South Florida

Tampa, Florida, United States, 33620

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55095

United States, Mississippi

The University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, New York

Long Island Jewish Medical Center

New Hyde Park, New York, United States, 11042

United States, North Carolina

PMG Research Inc.

Wilmington, North Carolina, United States, 28401

Piedmont Ear, Nose, & Throat Associates

Winston-Salem, North Carolina, United States, 27103

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Utah

Jean Brown Research

Murray, Utah, United States, 84107

Sponsors and Collaborators

Autifony Therapeutics Limited

Investigators

• Principal Investigator: Robert Frisina, PhD; Director Global Center for Hearing and Speech Research

More Information

• Responsible Party: Autifony Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT02345031
• Other Study ID Numbers: AUT022063
• First Posted: January 26, 2015
• Results First Posted: September 19, 2017
• Last Update Posted: August 9, 2018
• Last Verified: August 2018

Keywords provided by Autifony Therapeutics Limited:

hearing loss; speech-in-noise

Additional relevant MeSH terms:

Hearing Loss; Deafness; Presbycusis; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Hearing Loss, Sensorineural