A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP)

NCT04305184 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 0598-CL-0101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Chronic Tympanic Membrane Perforation

Keywords

ASP0598

Outcome Measures

Primary Outcomes (12)

• 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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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

  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.

  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.

  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).

  Baseline and week 12

Secondary Outcomes (12)

• Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD

  Week 8

• Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion

  Week 12

• Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD

  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

  Baseline and week 12

• Change From Baseline in TMP Size at Week 8 for SAD

  Baseline and week 8

Study Arms (8)

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 \[End of Study (EOS)\].

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).

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).

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).

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).

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).

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).

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).

Other: Placebo

Interventions

ASP0598 DRUG

ASP0598 Otic solution was administered onto the Tympanic Membrane (TM) through the external auditory canal via syringe.

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

Placebo OTHER

Placebo matched to ASP0598 Otic solution was administered onto the TM through the external auditory canal via syringe.

MAD: Placebo; SAD: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (10)

Stanford Hospital

Palo Alto, California, 94304, United States

Location

Breathe Clear Institute

Torrance, California, 90503, United States

Location

ENT and Allergy Associates of Florida

Boca Raton, Florida, 33487, United States

Location

Advanced ENT

New Albany, Indiana, 47150, United States

Location

Advanced ENT

Louisville, Kentucky, 40220, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Charlotte ENT Associates

Matthews, North Carolina, 28105, United States

Location

Piedmont ENT

Winston-Salem, North Carolina, 27103, United States

Location

Carolina ENT Clinic

Orangeburg, South Carolina, 29118, United States

Location

Richmond ENT

Richmond, Virginia, 23235, United States

Location

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Limitations and Caveats

Due to limitations of the TM imaging data as evaluated by the central reader, secondary endpoints related to change in TMP size could not be fully evaluated. Following SAD and MAD data review by DMC, the single dose of ASP0598 Otic Solution provided insufficient efficacy to open the single dose expansion study.

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc

astellas.resultsdisclosure@astellas.com

8008887704

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 12, 2020
• Study Start: September 10, 2020
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: November 25, 2024
• Results First Posted: February 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)