Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: ASP0598
    Topical Solution
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.
  • Drug: ASP0598
    Topical Solution
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.
  • Drug: ASP0598
    Topical Solution
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.
  • Drug: ASP0598
    Topical Solution
Placebo Comparator
Pooled Placebo in SAD
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
  • Drug: Matching Placebo
    Placebo Topical Solution
Placebo Comparator
Pooled Placebo in MAD
For each dose level ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
  • Drug: Matching Placebo
    Placebo Topical Solution
Placebo Comparator
Placebo in Single Dose Expansion
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
  • Drug: Matching Placebo
    Placebo Topical Solution
Placebo Comparator
Placebo in Multiple Dose Expansion
ASP0598 matching placebo onto the tympanic membrane through the external auditory canal via syringe.
  • Drug: Matching Placebo
    Placebo Topical Solution

Recruiting Locations

University of Arkansas
Little Rock, Arkansas 72205

Central California ENT
Fresno, California 93720

Stanford Hospital
Palo Alto, California 94304

Breathe Clear Institute
Torrance, California 90503

Colorado ENT & Allergy
Colorado Springs, Colorado 80909

George Washington University
Washington, District of Columbia 20037

ENT and Allergy Associates of Florida
Boca Raton, Florida 33487

University of Chicago
Chicago, Illinois 60637

Advanced ENT
New Albany, Indiana 47150

Advanced ENT
Louisville, Kentucky 40220

Tufts Medical Center
Boston, Massachusetts 02111

University of Michigan
Ann Arbor, Michigan 48109

Columbia University Medical Center
New York, New York 10032

Charlotte ENT Associates
Matthews, North Carolina 28105

Piedmont ENT
Winston-Salem, North Carolina 27103

Carolina ENT Clinic
Orangeburg, South Carolina 29118

University of Texas
Dallas, Texas 75235

Alamo ENT
San Antonio, Texas 78258

Richmond ENT
Richmond, Virginia 23235

More Details

NCT ID
NCT04305184
Status
Recruiting
Sponsor
Astellas Pharma Global Development, Inc.

Study Contact

Astellas Pharma Global Development, Inc.
800-888-7704;
Astellas.registration@astellas.com

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.