Back to resultsA Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
Primary Purpose
Chronic Tympanic Membrane Perforation
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ASP0598
Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Tympanic Membrane Perforation focused on measuring ASP0598
Eligibility Criteria
Inclusion Criteria:
- Subject has chronic tympanic membrane perforation (CTMP) documented as persisting longer than 3 months.
A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance starting at screening and for at least 28 days after investigational product (IP) application.
- Female subject must agree not to breastfeed starting at drug application on Day 1 and for at least 28 days after IP application.
- Female subject must not donate ova starting on Day 1 and for at least 28 days after investigational product (IP) application.
- A male subject with female partner(s) of child-bearing potential must agree to use contraception starting on Day 1 and for at least 28 days after IP application.
- A male subject must not donate sperm starting on Day 1 and for at least 28 days after IP application.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom from Day 1 and for at least 28 days after IP application.
- Subject must be willing and able to comply with the study requirements including refraining from using prohibited concomitant medications.
- Subject agrees not to participate in another interventional study during the study period.
Exclusion Criteria:
Subject has one of following conditions that may affect the ipsilateral side of the ear with chronic tympanic membrane perforation (CTMP):
- Perforation involving 3 or more quadrants.
- Pin hole perforation (only for the expansion cohort).
- Presence of tympanosclerosis adjacent to the perforation.
- Perforation involves malleus erosion.
- Absent malleus.
- Marginal perforation (i.e., involving the annulus or exposing the handle of malleus).
- Tympanic membrane perforation (TMP) caused by electric/slag/blast/burn injury.
- Post radiated TMP.
- History of tympanic membrane repair by any type of live tissue.
- Active otorrhea or active treatment for otorrhea within the last 3 months prior to Screening.
- Bellucci otorrhea grade 3 or above.
- Active external ear canal inflammation (otitis externa, dermatitis) or within the last 3 months prior to Screening.
- Active diagnosis of Eustachian Tube dysfunction or diagnosis within 6 months prior to Screening.
- Craniofacial abnormalities, History of head and neck surgery within the last 3 months prior to Screening, history of radiation to head and neck.
- Recent (within 2 weeks) diagnosis of upper respiratory tract infection.
- Presence or history of cholesteatoma.
- Presence of pars-flaccida or pars tensa retraction or adhesion.
- Presence or history of tumors of the middle or external ear.
- Contraindications to tympanic membrane closure.
- An audiometric finding indicates a characteristic of Carhart's notch which is an increase in bone conduction threshold with a peak at 2,000 hertz (Hz).
- Only hearing ear or better hearing ear and the contralateral ear ≥ 40 dB (decibels) by average four-frequency (500, 1000, 2000 and 4000 Hz).
- Whole circumference of the tympanic membrane perforation is not visible by endoscope.
- Presence/history of eosinophilic otitis media in either ear.
- Subject has a presence of adhesive otitis media in the contralateral ear.
- Subject has a presence of any wound healing systemic condition.
- Subject has Obstructive Sleep Apnea where the subject is required to use Continuous Positive Airway Pressure (CPAP) during the study period.
- Subject is exposed in their daily life to high volume of water into the ear canal (e.g., swimmer or surfer).
- Subject has health conditions that would prevent him/her from fulfilling the study requirements on the basis of medical history and laboratory test (Serum Chemistries, complete blood count [CBC] with Differential, Urinalysis) results at the screening visit.
- Subject is receiving any other investigational agents during study participation.
- Subject has any form of substance abuse, or psychiatric illness/social situations that would limit compliance with study requirements, or a condition that could invalidate communication.
- Subject has a known or suspected hypersensitivity to ASP0598, or any components of the formulation used.
- Subject has had previous exposure with ASP0598.
- Subject is unlikely to comply with the visits scheduled in the protocol.
Sites / Locations
- Stanford Hospital
- Breathe Clear Institute
- ENT and Allergy Associates of Florida
- Advanced ENT
- Advanced ENT
- University of Michigan
- Charlotte ENT Associates
- Piedmont ENT
- Carolina ENT Clinic
- Richmond ENT
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Placebo Comparator
Placebo Comparator
Arm Label
ASP0598 SAD
ASP0598 MAD
ASP0598 Single Dose Expansion
ASP0598 Multiple Dose Expansion
Pooled Placebo in SAD
Pooled Placebo in MAD
Placebo in Single Dose Expansion
Placebo in Multiple Dose Expansion
Arm Description
A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 4 dose levels.
Multiple topical applications of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels with additional treatment days.
A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels.
Multiple topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels with additional treatment days.
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
Outcomes
Primary Outcome Measures
Number of participants with Treatment Emergent Adverse Events (TEAEs) in SAD
An adverse event (AE) is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Number of participants with TEAEs of special interest in SAD
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in SAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in SAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in SAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in SAD
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Number of participants with Treatment Emergent Adverse Events (TEAEs) in single dose expansion
An AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Number of incidences of AEs of special interest in single dose expansion
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in single dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in single dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in single dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in single dose expansion
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Number of participants with Treatment Emergent Adverse Events (TEAEs) in MAD
AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Number of participants with TEAEs of special interest in MAD
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in MAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in MAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in MAD
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in MAD
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Number of participants with Treatment Emergent Adverse Events (TEAEs) in multiple dose expansion
An AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Number of incidences of AEs of special interest in multiple dose expansion
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in multiple dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in multiple dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in multiple dose expansion
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in multiple dose expansion
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Secondary Outcome Measures
Proportion of participants with complete closure of Tympanic Membrane Perforation (TMP) in SAD
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Change from baseline in the ratio of TMP size per total area of tympanic membrane in SAD
Ratio of TMP size per total area of tympanic membrane will be calculated.
Change from baseline in TMP size in SAD
TMP size calculation will be performed by central imaging vendor.
Proportion of participants with complete closure of TMP in single dose expansion
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Change from baseline in the ratio of TMP size per total area of tympanic membrane in single dose expansion
Ratio of TMP size per total area of tympanic membrane will be calculated.
Change from baseline in TMP size in single dose expansion
TMP size calculation will be performed by central imaging vendor.
Proportion of participants with complete closure of TMP in MAD
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Change from baseline in TMP size in MAD
TMP size calculation will be performed by central imaging vendor.
Change from baseline in the ratio of TMP size per total area of tympanic membrane in MAD
Ratio of TMP size per total area of tympanic membrane will be calculated.
Proportion of participants with complete closure of TMP in multiple dose expansion
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Change from baseline in the ratio of TMP size per total area of tympanic membrane in multiple dose expansion
Ratio of TMP size per total area of tympanic membrane will be calculated.
Change from baseline in TMP size in multiple dose expansion
TMP size calculation will be performed by central imaging vendor.
Full Information
NCT ID
NCT04305184
First Posted
March 10, 2020
Last Updated
July 11, 2023
Sponsor
Astellas Pharma Global Development, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04305184
Brief Title
A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
Official Title
A Phase 1/2, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of ASP0598 Otic Solution Following Topical Application Into the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of Efficacy
Study Start Date
September 10, 2020 (Actual)
Primary Completion Date
January 24, 2023 (Actual)
Study Completion Date
January 24, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of this study is to evaluate the safety and tolerability of ASP0598 Otic Solution. This study will also evaluate the efficacy of ASP0598 otic solution.
Detailed Description
This study will consist of a dose escalation (single ascending dose - SAD and multiple ascending dose- MAD) and dose expansion (single dose expansion and/or multiple dose expansion). Dose escalation will consist of up to 4 cohorts for single ascending dose (SAD) and up to 2 cohorts for multiple ascending dose (MAD) with different dose levels. For SAD, after randomization on Day 1, participants will receive ASP0598 Otic Solution or placebo administration into the affected ear. Participants will return to the site on days 2, 3, 8, 15, 29, and 57 [end of study (EOS)]. Day 3 evaluations will only be performed for cohorts 1, 2 and 3. For MAD, after randomization on Day 1, participants will receive ASP0598 Otic Solution or placebo administration into the affected ear and will receive additional treatments into the same ear on Days 15 and 29. Participants will return to the investigative site on Days 8, 15, 22, 29, 36, 57, and 85 (EOS). Dose expansion will be based on the safety and efficacy results from an interim analysis. An interim analysis will be conducted after completion of SAD and again after completion of MAD. If dose expansion is opened, 2 or 3 treatment groups will be selected. If 3 groups are selected, participants will be randomized in a 1:1:1 ratio of high dose ASP0598 Otic Solution, low dose ASP0598 Otic Solution, and Placebo. If 2 groups are selected, participants will be randomized in a 1:1 ratio of high dose ASP0598 Otic Solution and Placebo. For single dose expansion, after randomization on Day 1, participants will receive ASP0598 otic solution or placebo administration into the affected ear. Participants will return to the investigative site on days 15, 29, 57, and 85 (EOS). For multiple dose expansion, after randomization on Day 1, participants will receive ASP0598 Otic Solution or placebo administration into the affected ear. Participants will receive additional treatment in the same ear on Days 15 and 29. In cases where complete closure is confirmed on either Day 15 or Day 29, no additional treatment is required at those visit(s). Participants will return to the investigative site on Days 15, 29, 43, 57, 85 and 113 (EOS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Tympanic Membrane Perforation
Keywords
ASP0598
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ASP0598 SAD
Arm Type
Experimental
Arm Description
A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 4 dose levels.
Arm Title
ASP0598 MAD
Arm Type
Experimental
Arm Description
Multiple topical applications of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels with additional treatment days.
Arm Title
ASP0598 Single Dose Expansion
Arm Type
Experimental
Arm Description
A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels.
Arm Title
ASP0598 Multiple Dose Expansion
Arm Type
Experimental
Arm Description
Multiple topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels with additional treatment days.
Arm Title
Pooled Placebo in SAD
Arm Type
Placebo Comparator
Arm Description
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
Arm Title
Pooled Placebo in MAD
Arm Type
Placebo Comparator
Arm Description
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
Arm Title
Placebo in Single Dose Expansion
Arm Type
Placebo Comparator
Arm Description
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
Arm Title
Placebo in Multiple Dose Expansion
Arm Type
Placebo Comparator
Arm Description
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
Intervention Type
Drug
Intervention Name(s)
ASP0598
Intervention Description
Topical Solution
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Placebo Topical Solution
Primary Outcome Measure Information:
Title
Number of participants with Treatment Emergent Adverse Events (TEAEs) in SAD
Description
An adverse event (AE) is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Time Frame
Up to Day 57
Title
Number of participants with TEAEs of special interest in SAD
Description
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Time Frame
Up to Day 57
Title
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in SAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Time Frame
Baseline and Day 57
Title
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in SAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 57
Title
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in SAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 57
Title
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in SAD
Description
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Time Frame
Baseline and Day 57
Title
Number of participants with Treatment Emergent Adverse Events (TEAEs) in single dose expansion
Description
An AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Time Frame
Up to Day 85
Title
Number of incidences of AEs of special interest in single dose expansion
Description
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Time Frame
Up to Day 85
Title
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in single dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Time Frame
Baseline and Day 85
Title
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in single dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 85
Title
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in single dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 85
Title
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in single dose expansion
Description
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Time Frame
Baseline and Day 85
Title
Number of participants with Treatment Emergent Adverse Events (TEAEs) in MAD
Description
AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Time Frame
Up to Day 85
Title
Number of participants with TEAEs of special interest in MAD
Description
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Time Frame
Up to Day 85
Title
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in MAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Time Frame
Baseline and Day 85
Title
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in MAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 85
Title
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in MAD
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 85
Title
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in MAD
Description
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Time Frame
Baseline and Day 85
Title
Number of participants with Treatment Emergent Adverse Events (TEAEs) in multiple dose expansion
Description
An AE is any untoward medical occurrence in a subject administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of investigational product (IP) whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit. A drug-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator.
Time Frame
Up to Day 113
Title
Number of incidences of AEs of special interest in multiple dose expansion
Description
AEs of special interest include cholesteatoma or ear neoplasm, ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) and otitis media or otitis externa.
Time Frame
Up to Day 113
Title
Change from baseline in bone conduction hearing at 1 kHz by pure tone audiometry (PTA) in multiple dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems. Pure tone air conduction and bone conduction tests determine whether or not there is any hearing loss; what type of hearing loss it is (conductive, sensorineural or mixed hearing loss); the frequencies that are affected (configuration); magnitude of hearing loss (intensity) and whether hearing loss is unilateral or bilateral. The result is plotted on an audiogram, which is a graph displaying intensity as a function of frequency.
Time Frame
Baseline and Day 113
Title
Change from baseline in bone conduction hearing at 2 kHz by pure tone audiometry (PTA) in multiple dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 113
Title
Change from baseline in bone conduction hearing at 4 kHz by pure tone audiometry (PTA) in multiple dose expansion
Description
PTA is a behavioral test and generally the 1st quantitative hearing test done to assess the nature and degree of hearing loss in adults and in children. This measure involves the peripheral and central auditory systems.
Time Frame
Baseline and Day 113
Title
Change from baseline in Tinnitus Visual Analog Scale (TVAS) in multiple dose expansion
Description
TVAS is a scale for tinnitus loudness. Participants will be asked to rate their tinnitus on a scale of 0 to 10, where 0 means not at all strong or loud and 10 means extremely strong or loud tinnitus. A lower score means an improvement in tinnitus loudness.
Time Frame
Baseline and Day 113
Secondary Outcome Measure Information:
Title
Proportion of participants with complete closure of Tympanic Membrane Perforation (TMP) in SAD
Description
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Time Frame
Up to Day 57
Title
Change from baseline in the ratio of TMP size per total area of tympanic membrane in SAD
Description
Ratio of TMP size per total area of tympanic membrane will be calculated.
Time Frame
Baseline and Day 57
Title
Change from baseline in TMP size in SAD
Description
TMP size calculation will be performed by central imaging vendor.
Time Frame
Baseline and Day 57
Title
Proportion of participants with complete closure of TMP in single dose expansion
Description
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Time Frame
Up to Day 85
Title
Change from baseline in the ratio of TMP size per total area of tympanic membrane in single dose expansion
Description
Ratio of TMP size per total area of tympanic membrane will be calculated.
Time Frame
Baseline and Day 85
Title
Change from baseline in TMP size in single dose expansion
Description
TMP size calculation will be performed by central imaging vendor.
Time Frame
Baseline and Day 85
Title
Proportion of participants with complete closure of TMP in MAD
Description
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Time Frame
Up to Day 85
Title
Change from baseline in TMP size in MAD
Description
TMP size calculation will be performed by central imaging vendor.
Time Frame
Baseline and Day 85
Title
Change from baseline in the ratio of TMP size per total area of tympanic membrane in MAD
Description
Ratio of TMP size per total area of tympanic membrane will be calculated.
Time Frame
Baseline and Day 85
Title
Proportion of participants with complete closure of TMP in multiple dose expansion
Description
Tympanic membrane perforation is a perforation of tympanic membrane in the ear. TMP closure is defined as microscopic TMP closure without presence of pin hole. All images from each visit will be sent to a central imaging vendor for measurement and interpretation.
Time Frame
Up to Day 113
Title
Change from baseline in the ratio of TMP size per total area of tympanic membrane in multiple dose expansion
Description
Ratio of TMP size per total area of tympanic membrane will be calculated.
Time Frame
Baseline and Day 113
Title
Change from baseline in TMP size in multiple dose expansion
Description
TMP size calculation will be performed by central imaging vendor.
Time Frame
Baseline and Day 113
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject has chronic tympanic membrane perforation (CTMP) documented as persisting longer than 3 months.
A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR
WOCBP who agrees to follow the contraceptive guidance starting at screening and for at least 28 days after investigational product (IP) application.
Female subject must agree not to breastfeed starting at drug application on Day 1 and for at least 28 days after IP application.
Female subject must not donate ova starting on Day 1 and for at least 28 days after investigational product (IP) application.
A male subject with female partner(s) of child-bearing potential must agree to use contraception starting on Day 1 and for at least 28 days after IP application.
A male subject must not donate sperm starting on Day 1 and for at least 28 days after IP application.
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom from Day 1 and for at least 28 days after IP application.
Subject must be willing and able to comply with the study requirements including refraining from using prohibited concomitant medications.
Subject agrees not to participate in another interventional study during the study period.
Exclusion Criteria:
Subject has one of following conditions that may affect the ipsilateral side of the ear with chronic tympanic membrane perforation (CTMP):
Perforation involving 3 or more quadrants.
Pin hole perforation (only for the expansion cohort).
Presence of tympanosclerosis adjacent to the perforation.
Perforation involves malleus erosion.
Absent malleus.
Marginal perforation (i.e., involving the annulus or exposing the handle of malleus).
Tympanic membrane perforation (TMP) caused by electric/slag/blast/burn injury.
Post radiated TMP.
History of tympanic membrane repair by any type of live tissue.
Active otorrhea or active treatment for otorrhea within the last 3 months prior to Screening.
Bellucci otorrhea grade 3 or above.
Active external ear canal inflammation (otitis externa, dermatitis) or within the last 3 months prior to Screening.
Active diagnosis of Eustachian Tube dysfunction or diagnosis within 6 months prior to Screening.
Craniofacial abnormalities, History of head and neck surgery within the last 3 months prior to Screening, history of radiation to head and neck.
Recent (within 2 weeks) diagnosis of upper respiratory tract infection.
Presence or history of cholesteatoma.
Presence of pars-flaccida or pars tensa retraction or adhesion.
Presence or history of tumors of the middle or external ear.
Contraindications to tympanic membrane closure.
An audiometric finding indicates a characteristic of Carhart's notch which is an increase in bone conduction threshold with a peak at 2,000 hertz (Hz).
Only hearing ear or better hearing ear and the contralateral ear ≥ 40 dB (decibels) by average four-frequency (500, 1000, 2000 and 4000 Hz).
Whole circumference of the tympanic membrane perforation is not visible by endoscope.
Presence/history of eosinophilic otitis media in either ear.
Subject has a presence of adhesive otitis media in the contralateral ear.
Subject has a presence of any wound healing systemic condition.
Subject has Obstructive Sleep Apnea where the subject is required to use Continuous Positive Airway Pressure (CPAP) during the study period.
Subject is exposed in their daily life to high volume of water into the ear canal (e.g., swimmer or surfer).
Subject has health conditions that would prevent him/her from fulfilling the study requirements on the basis of medical history and laboratory test (Serum Chemistries, complete blood count [CBC] with Differential, Urinalysis) results at the screening visit.
Subject is receiving any other investigational agents during study participation.
Subject has any form of substance abuse, or psychiatric illness/social situations that would limit compliance with study requirements, or a condition that could invalidate communication.
Subject has a known or suspected hypersensitivity to ASP0598, or any components of the formulation used.
Subject has had previous exposure with ASP0598.
Subject is unlikely to comply with the visits scheduled in the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Global Development, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Breathe Clear Institute
City
Torrance
State/Province
California
ZIP/Postal Code
90503
Country
United States
Facility Name
ENT and Allergy Associates of Florida
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33487
Country
United States
Facility Name
Advanced ENT
City
New Albany
State/Province
Indiana
ZIP/Postal Code
47150
Country
United States
Facility Name
Advanced ENT
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40220
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Charlotte ENT Associates
City
Matthews
State/Province
North Carolina
ZIP/Postal Code
28105
Country
United States
Facility Name
Piedmont ENT
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Carolina ENT Clinic
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Facility Name
Richmond ENT
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
IPD Sharing Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
IPD Sharing Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Learn more about this trial
A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
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