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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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ClinicalTrials.gov Identifier: NCT04305184
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : September 1, 2021
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE March 10, 2020
First Posted Date  ICMJE March 12, 2020
Last Update Posted Date September 1, 2021
Actual Study Start Date  ICMJE September 10, 2020
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
  • Number of participants with Treatment Emergent Adverse Events (TEAEs) in SAD [ Time Frame: Up to Day 57 ]
    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 [ Time Frame: Up to Day 57 ]
    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 [ Time Frame: Baseline and Day 57 ]
    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 [ Time Frame: Baseline and Day 57 ]
    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 [ Time Frame: Baseline and Day 57 ]
    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 [ Time Frame: Baseline and Day 57 ]
    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 [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Up to Day 113 ]
    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 [ Time Frame: Up to Day 113 ]
    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 [ Time Frame: Baseline and Day 113 ]
    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 [ Time Frame: Baseline and Day 113 ]
    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 [ Time Frame: Baseline and Day 113 ]
    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 [ Time Frame: Baseline and Day 113 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Number of participants with Treatment Emergent Adverse Events (TEAEs) in dose escalation phase. [ Time Frame: Up to Day 57 ]
    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 dose escalation phase [ Time Frame: Up to Day 57 ]
    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 dose escalation phase [ Time Frame: Baseline and up to Day 57 ]
    Pure Tone Audiometry (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 dose escalation phase [ Time Frame: Baseline and up to Day 57 ]
    Pure Tone Audiometry (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 dose escalation phase [ Time Frame: Baseline and up to Day 57 ]
    Pure Tone Audiometry (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 dose escalation phase [ Time Frame: Baseline and up to Day 57 ]
    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 dose expansion phase. [ Time Frame: Up to Day 85 ]
    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 incidences of AEs of special interest in dose expansion phase [ Time Frame: Up to Day 85 ]
    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 dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    Pure Tone Audiometry (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 2 kHz by pure tone audiometry (PTA) in dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    Pure Tone Audiometry (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 dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    Pure Tone Audiometry (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 dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
  • Proportion of participants with complete closure of Tympanic Membrane Perforation (TMP) in SAD [ Time Frame: Up to Day 57 ]
    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 [ Time Frame: Baseline and Day 57 ]
    Ratio of TMP size per total area of tympanic membrane will be calculated.
  • Change from baseline in TMP size in SAD [ Time Frame: Baseline and Day 57 ]
    TMP size calculation will be performed by central imaging vendor.
  • Proportion of participants with complete closure of TMP in single dose expansion [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    Ratio of TMP size per total area of tympanic membrane will be calculated.
  • Change from baseline in TMP size in single dose expansion [ Time Frame: Baseline and Day 85 ]
    TMP size calculation will be performed by central imaging vendor.
  • Proportion of participants with complete closure of TMP in MAD [ Time Frame: Up to Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Baseline and Day 85 ]
    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 [ Time Frame: Up to Day 113 ]
    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 [ Time Frame: Baseline and Day 113 ]
    Ratio of TMP size per total area of tympanic membrane will be calculated.
  • Change from baseline in TMP size in multiple dose expansion [ Time Frame: Baseline and Day 113 ]
    TMP size calculation will be performed by central imaging vendor.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Proportion of participants with complete closure of Tympanic Membrane Perforation (TMP) in dose escalation phase [ Time Frame: Up to Day 57 ]
    Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle 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 for dose escalation phase [ Time Frame: Baseline up to Day 57 ]
    Ratio of TMP size per total area of tympanic membrane calculation will be performed by central imaging vendor.
  • Change from baseline in TMP size for dose escalation phase [ Time Frame: Baseline and up to Day 57 ]
    TMP size calculation will be performed by central imaging vendor.
  • Proportion of participants with complete closure of Tympanic Membrane Perforation (TMP) in dose expansion phase [ Time Frame: Up to Day 85 ]
    Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle 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 for dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    Ratio of TMP size per total area of tympanic membrane calculation will be performed by central imaging vendor.
  • Change from baseline in TMP size for dose expansion phase [ Time Frame: Baseline and up to Day 85 ]
    TMP size calculation will be performed by central imaging vendor.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
Official Title  ICMJE 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)
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Tympanic Membrane Perforation
Intervention  ICMJE
  • Drug: ASP0598
    Topical Solution
  • Drug: Matching Placebo
    Placebo Topical Solution
Study Arms  ICMJE
  • Experimental: ASP0598 SAD
    A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 4 dose levels.
    Intervention: Drug: ASP0598
  • Experimental: ASP0598 MAD
    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.
    Intervention: Drug: ASP0598
  • Experimental: ASP0598 Single Dose Expansion
    A single topical application of ASP0598 onto the tympanic membrane through the external auditory canal via syringe at up to 2 dose levels.
    Intervention: Drug: ASP0598
  • Experimental: ASP0598 Multiple Dose Expansion
    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.
    Intervention: Drug: ASP0598
  • Placebo Comparator: Pooled Placebo in SAD
    For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
    Intervention: Drug: Matching Placebo
  • Placebo Comparator: Pooled Placebo in MAD
    For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
    Intervention: Drug: Matching Placebo
  • Placebo Comparator: Placebo in Single Dose Expansion
    ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
    Intervention: Drug: Matching Placebo
  • Placebo Comparator: Placebo in Multiple Dose Expansion
    ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
    Intervention: Drug: Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 18, 2020)
114
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)
59
Estimated Study Completion Date  ICMJE February 28, 2023
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Hz.
    • Only hearing or better hearing ear.
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Astellas Pharma Global Development, Inc. 800-888-7704; Astellas.registration@astellas.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04305184
Other Study ID Numbers  ICMJE 0598-CL-0101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
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.
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.
URL: https://www.clinicalstudydatarequest.com
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP