None listed
Conditions
Brief summary
This is a phase 1 safety study performed in male or female adult participants with an established diagnosis of severe to profound sensorineural hearing loss that meets the criteria for cochlear implantation and the participant has already chosen to undergo cochlear implant surgery. Approximately 13 participants will be enrolled in the study in one of three groups and will obtain either IP (investigational Product - FX-322) or placebo (in total 5 participants in group 1 - 3 active and 2 placebo - and 4 participants in group 2 and group 3 -3 active and 1 placebo). Assessed will be the diffusion of FX-322 from the middle ear, across the oval and round window membranes, and into the cochlear fluid (perilymph) as well as the tolerability of intratympanic injection of FX-322. In addition the pharmacokinetic (PK) profile of FX-322 will be assessed to determine the systemic exposure to FX-322. To assess safety by the evaluation of treatment-emergent adverse events (TEAEs); physical examination; Visual Analog Scale for pain, Tinnitus Visual Analog Scale (TVAS) and the Tinnitus Handicap Index (THI): to assess potential to cause, exacerbate or ameliorate tinnitus, and Vertigo Symptom Scale (VSS) Questionnaire and Dizziness Handicap Index (DHI): to assess effects on the vestibular system. Blood samples for determination of plasma FX-322 concentrations will be drawn pre-dose and post-dose at 1, 2, 4, and 6 hours on Day 1. Subjects will have the ~24 hour blood draw prior to discharge from the hospital. On post injection Day 3, the subjects will have their ~72 hour blood draw taken at their home. The duration of the study is 10 months.
Interventions
The study will consist of 3 groups. The first group will have 5 participants, the other groups 4 participants each undergoing cochlear implantation. Both the placebo and FX-322 will be administered by intratympanic injection in the ear to be implanted. All participants will be injected once with an identical volume (0.2 mL)
into the middle ear. This injection will be performed by a specialist and qualified cochlear implant surgeon. The participants will differ in obtaining Placebo (12-24 hours p
The study will consist of 3 groups. The first group will have 5 participants, the other groups 4 participants each undergoing cochlear implantation. Both the placebo and FX-322 will be administered by intratympanic injection in the ear to be implanted. All participants will be injected once with an identical volume (0.2 mL) into the middle ear. This injection will be performed by a specialist and qualified cochlear implant surgeon. The participants will differ in obtaining Placebo (12-24 hours prior to implantation) or FX-322 (18mg) and the time window for the injection (either 12-24 hours prior to the surgery, 3-5 hours prior to surgery or 0.5-2 hours prior to the surgery). The exact time of injection is based on hospital logistics. Group 1 will have the first two participants allocated to placebo and three FX-322. .participants. Group 2 and Group 3 each will have one placebo participant and three FX-322 participants. The participants in each group is based on hospital logistics. There is no dose change The reason for forming 3 groups is to have a safety review after each group . The participants will all be followed 1-4 weeks after the cochlear implantation. Participants must be adult and audiometric threshold of 80 decibel [dB] hearing loss [HL] or poorer at 500 Hertz [Hz])
Sponsors
Frequency Therapeutics Pty LTD
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female adult subjects with an established diagnosis of severe to profound sensorineural hearing loss audiometric threshold of 80 dB HL or poorer at 500 Hz that meets the criteria for cochlear implantation and the subject has already chosen to undergo cochlear implant surgery. 2. Written informed consent prior to participation 3. English as the primary language 4. Willingness and ability to comply with scheduled visits, ear examination, drug administration plan, auditory and laboratory tests, study restrictions, and all study procedures. 5. Females of child bearing potential must have a negative urine pregnancy test at Screening and Day 1 and agree to comply with using a highly effective form of birth control for the duration of the study (eg, abstinence, oral contraceptive, intrauterine device [(IUD)], barrier contraception [condom], tubal ligation, hysterectomy, bilateral oophorectomy or vasectomized partner). Males must agree to use a highly effective method of birth control with female partner(s) and must not donate sperm for the duration of the study.
Exclusion criteria
1. Current use or contraindication to FX-322 or its components. 2. Current use of drugs known to have drug-drug interactions with FX-322 or its components. 3. Persistent perforation of tympanic membrane or other tympanic membrane disorder that would interfere with the delivery and safety assessment of an intra -tympanic medication or reasonably be suspected to affect tympanic membrane healing after injection. 4. Any conductive component defined as air-bone gaps >10 dB at two or more frequencies 5. History of chronic otitis media (e.g., history of multiple perforated eardrums) or ear surgery of any kind as an adult (age 18 years or older) 6. History of vestibular symptoms, at the discretion of the investigator 7. History of clinically significant systemic autoimmune disease (rheumatoid, arthritis, Sjogren’s, multiple sclerosis) 8. History of head or neck radiation treatment or exposure 9. Exposure to another investigational drug within 28 days prior to start of study treatment or ongoing participation in any other therapeutic clinical trial with an investigational drug.
Outcome results
None listed