Chronic Tympanic Membrane PerforationPhase 1/2NCT04305184
A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)
A Phase 1/2 study testing ASP0598 in people with Chronic Tympanic Membrane Perforation, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.
Trial summary
The primary purpose of this study was to evaluate the safety and tolerability of ASP0598 Otic Solution. This study also evaluated the efficacy of ASP0598 otic solution. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Tympanic Membrane Perforation
- What is being tested?
- ASP0598
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 10 sitesUnited States
- Study dates
- 10 Sep 2020to 24 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 34Show fewer
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Michigan
Ann Arbor, Michigan, 48109
ENT and Allergy Associates of Florida
Boca Raton, Florida, 33487
Advanced ENT
Louisville, Kentucky, 40220
Charlotte ENT Associates
Matthews, North Carolina, 28105
Advanced ENT
New Albany, Indiana, 47150
Carolina ENT Clinic
Orangeburg, South Carolina, 29118
Stanford Hospital
Palo Alto, California, 94304
Richmond ENT
Richmond, Virginia, 23235
Breathe Clear Institute
Torrance, California, 90503
Piedmont ENT
Winston-Salem, North Carolina, 27103
About this study
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)
The primary purpose of this study was to evaluate the safety and tolerability of ASP0598 Otic Solution. This study also evaluated the efficacy of ASP0598 otic solution.
Read the detailed description
This study consisted 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 consisted 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 received ASP0598 Otic Solution or placebo administration into the affected ear. Participants returned to the site on days 2, 3, 8, 15, 29, and 57 [end of study (EOS)]. Day 3 evaluations were only performed for cohorts 1, 2 and 3. For MAD, after randomization on Day 1, participants received ASP0598 Otic Solution or placebo administration into the affected ear and received additional treatments into the same ear on Days 15 and 29. Participants returned to the investigative site on Days 8, 15, 22, 29, 36, 57, and 85 (EOS). Dose expansion was based on the safety and efficacy results from an interim analysis. An interim analysis was conducted after completion of SAD and again after completion of MAD. The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of SAD and MAD parts of the study by the DMC per the Interim Analysis Plan.
- Conditions
- Chronic Tympanic Membrane Perforation
- Being tested
- ASP0598, Placebo
- Keywords
- ASP0598
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP0598Drug
ASP0598 Otic solution was administered onto the Tympanic Membrane (TM) through the external auditory canal via syringe.
PlaceboOther
Placebo matched to ASP0598 Otic solution was administered onto the TM through the external auditory canal via syringe.
| Study group | Role | What they receive |
|---|---|---|
| Single Ascending Dose (SAD): 0.03 mcg | Experimental | Participants received single dose of 0.03 microgram (mcg) ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 [End of Study (EOS)]. Receives: Drug: ASP0598 |
| SAD: 0.15 mcg | Experimental | Participants received single dose of 0.15 mcg ASP0598 Otic Solution into the affected ear on Day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). Receives: Drug: ASP0598 |
| SAD: 0.75 mcg | Experimental | Participants received single dose of 0.75 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). Receives: Drug: ASP0598 |
| SAD: 2.25 mcg | Experimental | Participants received single dose of 2.25 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). Receives: Drug: ASP0598 |
| SAD: Placebo | Placebo comparator | Participants received single dose of placebo matched to ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). Receives: Other: Placebo |
| Multiple Ascending Dose (MAD): 0.75 mcg | Experimental | Participants received multiple doses of 0.75 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). Receives: Drug: ASP0598 |
| MAD: 2.25 mcg | Experimental | Participants received multiple doses of 2.25 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). Receives: Drug: ASP0598 |
| MAD: Placebo | Placebo comparator | Participants received multiple doses of placebo matched to ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD
An adverse event (AE) is any untoward medical occurrence in a participant administered an investigational product (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 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.
Measured: From first dose up to day 57
Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Measured: From first dose up to day 57
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with any ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported.
Measured: From first dose up to day 57
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
Measured: From first dose up to day 57
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Measured: Baseline and week 8
Change From Baseline in TVAS at Week 8/EOS in SAD
TVAS was used by participants to rate their tinnitus at baseline and week 8. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
Measured: Baseline and week 8
Number of Participants With TEAEs in MAD
An AE is any untoward medical occurrence in a participant 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 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.
Measured: From first dose up to day 85
Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Measured: From first dose up to day 85
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with any Ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported
Measured: From first dose up to day 85
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
Measured: From first dose up to day 85
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Measured: Baseline and week 12
Change From Baseline in TVAS at Week 12/EOS in MAD
TVAS was used by participants to rate their tinnitus at baseline and week 12. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
Measured: Baseline and week 12
Secondary outcomes (12)
Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD
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.
Measured: Week 8
Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion
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.
Measured: Week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Measured: Baseline and week 8
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for Dose Expansion
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and was measured by percentage.
Measured: Baseline and week 12
Change From Baseline in TMP Size at Week 8 for SAD
TMP size calculation was be performed by central imaging vendor.
Measured: Baseline and week 8
Change From Baseline in TMP Size at Week 12 for Dose Expansion
TMP size calculation was be performed by central imaging vendor.
Measured: Baseline and week 12
Number of Participants With Complete Closure of TMP at Week 12 for MAD
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.
Measured: Week 12
Number of Participants With Complete Closure of TMP at Week 16 for Dose Expansion
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.
Measured: Week 16
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Measured: Baseline and week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 16 for Dose Expansion
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Measured: Baseline and week 16
Change From Baseline in TMP Size at Week 12 for MAD
TMP size calculation was be performed by central imaging vendor.
Measured: Baseline and week 12
Change From Baseline in TMP Size at Week 16 for Dose Expansion
TMP size calculation was be performed by central imaging vendor.
Measured: Baseline and week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start10 Sep 2020
- Primary completion24 Jan 2023
- Study completion24 Jan 2023
Why it stopped: Lack of Efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Tympanic Membrane PerforationStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305184
- Sponsor's protocol ID
- 0598-CL-0101
- Status last verified
- Nov 2024
- First submitted
- 10 Mar 2020
- Last updated
- 25 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04305184
- Acronym / sponsor ID
- 0598-CL-0101
- Conditions
- Chronic Tympanic Membrane Perforation
- Keywords
- ASP0598
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Efficacy
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 24 Jan 2023 (actual)
- First posted
- 12 Mar 2020 (actual)
- Results
- Posted 7 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study was to evaluate the safety and tolerability of ASP0598 Otic Solution. This study also evaluated the efficacy of ASP0598 otic solution.
Detailed description
This study consisted 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 consisted 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 received ASP0598 Otic Solution or placebo administration into the affected ear. Participants returned to the site on days 2, 3, 8, 15, 29, and 57 [end of study (EOS)]. Day 3 evaluations were only performed for cohorts 1, 2 and 3. For MAD, after randomization on Day 1, participants received ASP0598 Otic Solution or placebo administration into the affected ear and received additional treatments into the same ear on Days 15 and 29. Participants returned to the investigative site on Days 8, 15, 22, 29, 36, 57, and 85 (EOS). Dose expansion was based on the safety and efficacy results from an interim analysis. An interim analysis was conducted after completion of SAD and again after completion of MAD. The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of SAD and MAD parts of the study by the DMC per the Interim Analysis Plan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Single Ascending Dose (SAD): 0.03 mcg | Experimental | Drug: ASP0598Participants received single dose of 0.03 microgram (mcg) ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 [End of Study (EOS)]. |
| SAD: 0.15 mcg | Experimental | Drug: ASP0598Participants received single dose of 0.15 mcg ASP0598 Otic Solution into the affected ear on Day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). |
| SAD: 0.75 mcg | Experimental | Drug: ASP0598Participants received single dose of 0.75 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). |
| SAD: 2.25 mcg | Experimental | Drug: ASP0598Participants received single dose of 2.25 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). |
| SAD: Placebo | Placebo comparator | Other: PlaceboParticipants received single dose of placebo matched to ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). |
| Multiple Ascending Dose (MAD): 0.75 mcg | Experimental | Drug: ASP0598Participants received multiple doses of 0.75 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). |
| MAD: 2.25 mcg | Experimental | Drug: ASP0598Participants received multiple doses of 2.25 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). |
| MAD: Placebo | Placebo comparator | Other: PlaceboParticipants received multiple doses of placebo matched to ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- 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.
Key exclusion criteria (34 listed)
- Subject has one of following conditions that may affect the ipsilateral side of the ear with chronic tympanic membrane perforation (CTMP):
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASP0598ASP0598 Otic solution was administered onto the Tympanic Membrane (TM) through the external auditory canal via syringe. | Drug | MAD: 2.25 mcg, Multiple Ascending Dose (MAD): 0.75 mcg, SAD: 0.15 mcg, SAD: 0.75 mcg, SAD: 2.25 mcg, Single Ascending Dose (SAD): 0.03 mcg |
| PlaceboPlacebo matched to ASP0598 Otic solution was administered onto the TM through the external auditory canal via syringe. | Other | MAD: Placebo, SAD: Placebo |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD
Time frame: From first dose up to day 57
An adverse event (AE) is any untoward medical occurrence in a participant administered an investigational product (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 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.
Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD
Time frame: From first dose up to day 57
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD
Time frame: From first dose up to day 57
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with any ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported.
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD
Time frame: From first dose up to day 57
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD
Time frame: Baseline and week 8
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Change From Baseline in TVAS at Week 8/EOS in SAD
Time frame: Baseline and week 8
TVAS was used by participants to rate their tinnitus at baseline and week 8. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
Number of Participants With TEAEs in MAD
Time frame: From first dose up to day 85
An AE is any untoward medical occurrence in a participant 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 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.
Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD
Time frame: From first dose up to day 85
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD
Time frame: From first dose up to day 85
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with any Ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD
Time frame: From first dose up to day 85
An AE is any untoward medical occurrence in a participant 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 IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD
Time frame: Baseline and week 12
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Change From Baseline in TVAS at Week 12/EOS in MAD
Time frame: Baseline and week 12
TVAS was used by participants to rate their tinnitus at baseline and week 12. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
12 secondary outcomes
Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD
Time frame: Week 8
Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion
Time frame: Week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD
Time frame: Baseline and week 8
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for Dose Expansion
Time frame: Baseline and week 12
Change From Baseline in TMP Size at Week 8 for SAD
Time frame: Baseline and week 8
Change From Baseline in TMP Size at Week 12 for Dose Expansion
Time frame: Baseline and week 12
Number of Participants With Complete Closure of TMP at Week 12 for MAD
Time frame: Week 12
Number of Participants With Complete Closure of TMP at Week 16 for Dose Expansion
Time frame: Week 16
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD
Time frame: Baseline and week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 16 for Dose Expansion
Time frame: Baseline and week 16
Change From Baseline in TMP Size at Week 12 for MAD
Time frame: Baseline and week 12
Change From Baseline in TMP Size at Week 16 for Dose Expansion
Time frame: Baseline and week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Link to results and other applicable study documents on the Astellas Clinical Trials websiteLink provided by the sponsor.
- Link to plain language summary of the study on the Trial Results Summaries websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Astellas Pharma Global Development, Inc.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ASP0598 in people with Chronic Tympanic Membrane Perforation, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD (time frame: From first dose up to day 57). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.