AM-101 in the Treatment of Acute Tinnitus 3 (TACTT3)

Efficacy and Safety of AM-101 in the Treatment of Acute Peripheral Tinnitus 3

The purpose of this research study is to test the safety and effectiveness of the study drug, AM-101. AM-101 is tested for the treatment of tinnitus that started as the result of an injury to the inner ear or due to middle ear inflammation (otitis media). Subjects with tinnitus can take part in the study, if their tinnitus started within the last 3 months or within the last >3 to 6 months.

Study Overview

• Status: Completed
• Conditions: Tinnitus
• Intervention / Treatment: Drug: AM-101; Drug: Placebo

Detailed Description

This phase III study is assessing the drug's safety and is aiming to demonstrate efficacy of repeated intratympanic AM-101 injections in the treatment of acute peripheral tinnitus (up to 3 months (Stratum A), or between >3 and 6 months (Stratum B) from onset).

• Study Type: Interventional
• Enrollment (Actual): 893
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany
    • Please check the study webpage below for a study site list

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Persistent subjective peripheral tinnitus (unilateral or bilateral) following traumatic cochlear injury (acute acoustic trauma, blast trauma, middle ear surgery, inner ear barotrauma, tympanic membrane trauma) or otitis media with onset no longer than 3 months (Stratum A) or between >3 months and 6 months (Stratum B) prior to randomization, as documented by medical report or by documented medical history. Upon implementation of protocol amendment 6, subjects with tinnitus following traumatic cochlear injury will only be eligible if they are affected only unilaterally.
2. Age ≥ 18 years and ≤ 75 years;
3. Negative pregnancy test (woman of childbearing potential);
4. Willing and able to use adequate hearing protection, respectively to refrain from engaging in activities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured;
5. Willing and able to protect ear canal and middle ear from water exposure as long as tympanic membrane is not fully closed.

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

1. Fluctuating tinnitus;
2. Intermittent tinnitus;
3. Tinnitus resulting from traumatic head or neck injury;
4. Presence of chronic tinnitus;
5. Meniere's Disease, history of endolymphatic hydrops, or history of fluctuating hearing loss;
6. History of repeated idiopathic sudden sensorineural hearing loss or history of acoustic neuroma;
7. Ongoing acute or chronic otitis media or otitis externa;
8. Other treatment of tinnitus for the study duration;
9. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe, abnormal drug reaction;
10. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study;
11. Women of childbearing potential who are unwilling or unable to practice contraception, such as hormonal contraceptives, double barrier, sexual abstinence or intercourse with a partner who has been vasectomised for at least three months;
12. Concurrent participation in another clinical study or participation in another clinical study within 30 days prior to randomization.

Other protocol-defined exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AM-101 injection; AM-101	Drug: AM-101; AM-101 gel for intratympanic injection
Placebo Comparator: Placebo injection; Placebo	Drug: Placebo; Placebo gel for intratympanic injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoint - alternate primary efficacy endpoints: Tinnitus Functional Index (TFI)	Improvement in TFI total score	Baseline to Day 84
Efficacy endpoint - alternate primary efficacy endpoints: Patient-reported Tinnitus loudness on a Numerical Rating Scale (TLQ NRS loudest)	Improvement in TLQ NRS loudest	Baseline to Day 84
Safety endpoint: Hearing threshold	Occurrence of deterioration in hearing threshold >= 15 decibel (dB) at the average of two contiguous test frequencies (air conduction) in the treated ear(s)	Baseline to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoint - TFI	Improvement in TFI total score	Baseline to Day 10 and Day 35
Efficacy endpoint - TLQ NRS loudest	Improvement in patient-reported tinnitus loudness	Baseline to Day 10 and Day 35
Efficacy endpoint - patient-reported tinnitus annoyance (TAQ NRS worst)	Improvement in TAQ NRS worst	Baseline to Day10, Day 35 and Day 84
Efficacy endpoint - TFI sleep score	Improvement in TFI sleep score. The subscale "sleep" will be evaluated only for subjects with a TFI Sleep score greater than 0 at baseline.	Baseline to Day10, Day 35 and Day 84
Efficacy endpoint - Patient global impression of change in tinnitus severity (PGIC Tinnitus)	Patient global impression of change in tinnitus severity	at Day10, Day 35 and Day 84
Safety endpoint - Hearing threshold	Occurrence of deterioration in hearing threshold >= 15 dB at the average of two contiguous test frequencies in the treated ear(s)	Baseline to Day 1, Day 2, Day 10 and Day 84
Safety endpoint - Hearing threshold	Difference in occurrence of deterioration in hearing threshold >= 15 dB at the average of two contiguous test frequencies between the treated and untreated contralateral ear (subjects with unilaterally treated tinnitus only)	Baseline to Day 1, Day 2, Day 10 and Day 84
Safety endpoint - AEs and SAEs	Occurence and severity of adverse events (AEs) and serious adverse Events (SAEs), differentiated by relatedness, and by treatment-emergence and procedure-emergence	Up to Day 84

Collaborators and Investigators

• Sponsor: Auris Medical AG

Publications and helpful links

Helpful Links

• Link to Result entry in clinicaltrialsregister.eu

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 28, 2017
• Study Completion (Actual): December 28, 2017

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimated): January 20, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: AM-101-CL-12-02