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

• Sponsor: Autifony Therapeutics Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02345031
• Collaborator: (none)
• Enrollment: 78
• Locations: 13
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 6
• Patients Per Site Per Month: 0.4

Study Details

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
• 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: Jan 1, 2015
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Jun 1, 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 Names: 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 Names: Comparator

Outcome Measures

Primary Outcome Measures

1. Change in Hearing Loss After 4 Weeks of Treatment [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 [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 [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 [42 Days]

   Number of Subjects With At Least One Treatment Emergent Adverse Event

4. Pharmacokinetic of AUT00063, Plasma Levels [28 Days]

   Exposure of AUT00063 ng/ml, in plasma levels at Day 28

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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

	Site	City	State	Country	Postal Code
1	Sacramento ENT	Sacramento	California	United States	95815
2	Colorado ENT and Allergy	Colorado Springs	Colorado	United States	80909
3	ENT Associates of South Florida	Boca Raton	Florida	United States	33487
4	QPS MRA (Miami Research Associates)	Miami	Florida	United States	33143
5	University of South Florida	Tampa	Florida	United States	33620
6	University of Louisville	Louisville	Kentucky	United States	40202
7	Mayo Clinic	Rochester	Minnesota	United States	55095
8	The University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
9	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11042
10	PMG Research Inc.	Wilmington	North Carolina	United States	28401
11	Piedmont Ear, Nose, & Throat Associates	Winston-Salem	North Carolina	United States	27103
12	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
13	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Autifony Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT02345031
• Other Study ID Numbers: AUT022063
• First Posted: Jan 26, 2015
• Last Update Posted: Aug 9, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Autifony Therapeutics Limited: hearing loss; speech-in-noise
• Additional relevant MeSH terms: Hearing Loss; Deafness; Presbycusis

Study Results

Participant Flow

Arm/Group Title	AUT00063 (600 mg Capsules)	(AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Period Title: Overall Study
STARTED	38	40
COMPLETED	37	39
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	AUT00063 (600 mg Capsules)	(AUT00063 Placebo Capsules)	Total
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks	Total of all reporting groups
Overall Participants	38	40	78
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 39.5%	13 32.5%	28 35.9%
>=65 years	22 57.9%	26 65%	48 61.5%
Sex: Female, Male (Count of Participants)
Female	15 39.5%	17 42.5%	32 41%
Male	22 57.9%	22 55%	44 56.4%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	36 94.7%	38 95%	74 94.9%
Black/African-American	1 2.6%	1 2.5%	2 2.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic Or Latino	1 2.6%	0 0%	1 1.3%
Not Hispanic Or Latino	36 94.7%	39 97.5%	75 96.2%
Region of Enrollment (Count of Participants)
United States	38 100%	40 100%	78 100%
QuickSIN SNR-50 Score (dB) (decibels (dB)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [decibels (dB)]	7.00 (1.963)	7.11 (1.991)	7.06 (1.965)

Outcome Measures

1. Primary Outcome

Title	Change in Hearing Loss After 4 Weeks of Treatment
Description	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).
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AUT00063 (600 mg Capsules)	(AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Measure Participants	37	39
Least Squares Mean (95% Confidence Interval) [decibels (dB)]	-1.114	-1.914

2. Secondary Outcome

Title	Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28
Description	Final Average GDT Across-Channel at Day 28: Change from Baseline; FAS Population
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AUT00063 (600 mg Capsules)	(AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Measure Participants	35	37
Least Squares Mean (95% Confidence Interval) [ms]	-2.978	-10.72

3. Secondary Outcome

Title	Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28
Description	Final Average GDT Within-Channel at Day 28: Change from Baseline; FAS Population
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AUT00063 (600 mg Capsules)	(AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Measure Participants	36	39
Least Squares Mean (95% Confidence Interval) [ms]	4.452	5.526

4. Secondary Outcome

Title	To Further Investigate the Safety and Tolerability Profile of Repeat Administration of AUT00063 by Assessing Vital Signs, Physical Examination, Laboratory Exams and ECG
Description	Number of Subjects With At Least One Treatment Emergent Adverse Event
Time Frame	42 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AUT00063 (600 mg Capsules)	Placebo (AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Measure Participants	38	40
Count of Participants [Participants]	23 60.5%	24 60%

5. Secondary Outcome

Title	Pharmacokinetic of AUT00063, Plasma Levels
Description	Exposure of AUT00063 ng/ml, in plasma levels at Day 28
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AUT00063 (600 mg Capsules)	Placebo
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks	3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
Measure Participants	36	36
Mean (Standard Deviation) [ng]	3470.61 (1290.679)	0 (0)

Adverse Events

Time Frame	The recording period for Adverse Events is the period starting from the Informed Consent signature until the safety close out visit or subject's study participation ends; a total duration of up to 10 weeks.
Arm/Group Title	AUT00063 (600 mg Capsules)		Placebo (AUT00063 Placebo Capsules)
Arm/Group Description	3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks AUT00063: 600 mg, orally, once a day, for 4 weeks		3 capsules of placebo, to take orally once daily with food for 4 weeks Placebo: orally, once a day, for 4 weeks
All Cause Mortality
	AUT00063 (600 mg Capsules)		Placebo (AUT00063 Placebo Capsules)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/40 (0%)
Serious Adverse Events
	AUT00063 (600 mg Capsules)		Placebo (AUT00063 Placebo Capsules)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		1/40 (2.5%)
Injury, poisoning and procedural complications
Alcohol poisoning	0/38 (0%)	0	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	AUT00063 (600 mg Capsules)		Placebo (AUT00063 Placebo Capsules)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/38 (47.4%)		21/40 (52.5%)
Ear and labyrinth disorders
Tinnitus	4/38 (10.5%)		3/40 (7.5%)
Gastrointestinal disorders
Diarrhoea	3/38 (7.9%)		2/40 (5%)
Nausea	2/38 (5.3%)		3/40 (7.5%)
General disorders
Fatigue	2/38 (5.3%)		0/40 (0%)
Infections and infestations
Gastroenteritis	0/38 (0%)		2/40 (5%)
Upper respiratory tract infection	3/38 (7.9%)		2/40 (5%)
Investigations
Blood triglycerides increased	2/38 (5.3%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/38 (2.6%)		3/40 (7.5%)
Nervous system disorders
Dizziness	6/38 (15.8%)		1/40 (2.5%)
Headache	4/38 (10.5%)		5/40 (12.5%)
Somnolence	3/38 (7.9%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Sinus Congestion	1/38 (2.6%)		2/40 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.