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Trial registered on ANZCTR


Registration number
ACTRN12617000704392
Ethics application status
Approved
Date submitted
28/03/2017
Date registered
16/05/2017
Date last updated
9/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
First in human safety study of FX-322 in adults undergoing cochlear implantation.
Scientific title
First in human safety study of FX-322 in adults undergoing cochlear implantation.
Secondary ID [1] 291482 0
FX322-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hearing loss 302543 0
Condition category
Condition code
Ear 302082 302082 0 0
Deafness

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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])
Intervention code [1] 297549 0
Treatment: Drugs
Comparator / control treatment
Two participants of group 1 obtain placebo. One participant of group 2 and group 3 obtain Placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 301518 0
To assess diffusion of FX-322 from the middle ear, across the oval and round window membranes, and into the cochlear fluid (perilymph). The concentration of FX-322 will be analysed from the perilymph fluid and blood plasma by standard laboratory methods.
Timepoint [1] 301518 0
Perilymph fluid is taken in surgery only. Blood plasma is taken at baseline and screening (to prove no FX-322 is present) and 1,2,4,6, 24h and 72h post injection.
Primary outcome [2] 301824 0
To assess the tolerability of intratympanic injection of FX-322. This is evaluated via 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)
Timepoint [2] 301824 0
The tolerability will be assessed by comparing baseline assessments to the to the same assessments completed just prior to surgery (ie 12-24 hours, 3-5 hours or 0.5-2 hours post injection depending on when the FX-322 or Placebo injection was given).
Secondary outcome [1] 332913 0
To assess safety by the evaluation of treatment-emergent adverse events (TEAEs). No adverse events are known as of today.
Timepoint [1] 332913 0
Evaluating of treatment-emergent adverse events (TEAEs) will be completed by evaluating results from at the day of injection, surgery, 24h post injection, 72h post injection and 1-4 weeks after implantation depending on the hospital logistics to baseline values.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
There will be three study groups with no change between the groups in terms of
doses or treatment protocol. The reason for forming 3 groups is to have a safety review after each group . Two participants are allocated to placebo in group 1 and one participant in group 2 and 3 is allocated to placebo at one time window (12-24 hours prior
to surgery) and three participants are allocated to FX-322 at three different time windows (either 12-24 hours prior to the surgery, 3-5 hours prior to surgery and or 0.5-2 hours prior to the surgery).
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
For this explorative study, no prospective calculations of statistical power have been made..

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
22/05/2017
Actual
30/05/2017
Date of last participant enrolment
Anticipated
28/01/2018
Actual
Date of last data collection
Anticipated
28/02/2018
Actual
Sample size
Target
13
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7693 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment hospital [2] 7694 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 15614 0
3002 - East Melbourne
Recruitment postcode(s) [2] 15615 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 295962 0
Hospital
Name [1] 295962 0
The Royal Victorian Eye and Ear Hospital
Country [1] 295962 0
Australia
Funding source category [2] 295965 0
Hospital
Name [2] 295965 0
St Vincent’s Private Hospital
Country [2] 295965 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Frequency Therapeutics Pty LTD
Address
Level 19, HWT Tower, 40 City Road
Southbank Victoria
Country
Australia
Secondary sponsor category [1] 294849 0
Commercial sector/Industry
Name [1] 294849 0
Clinical Network Services
Address [1] 294849 0
Level 4, Jephson Street
Toowong, QLD 4066
Country [1] 294849 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297233 0
The Royal Victorian Eye & Ear Hospital Human Research & Ethics Committee
Ethics committee address [1] 297233 0
32 Gisborne Street, East Melbourne, VIC 3002
Ethics committee country [1] 297233 0
Australia
Date submitted for ethics approval [1] 297233 0
06/02/2017
Approval date [1] 297233 0
10/04/2017
Ethics approval number [1] 297233 0
Ethics committee name [2] 297237 0
St Vincent’s Hospital Melbourne Human Research Committee
Ethics committee address [2] 297237 0
41 Victoria Parade, Fitzroy VIC 3065
Ethics committee country [2] 297237 0
Australia
Date submitted for ethics approval [2] 297237 0
15/12/2016
Approval date [2] 297237 0
01/03/2017
Ethics approval number [2] 297237 0
HREC/16/SVHM/275

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73406 0
Prof Stephen O'Leary
Address 73406 0
Royal Victorian Eye & Ear Hospital,
32 Gisborne St, East Melbourne VIC 3002
Country 73406 0
Australia
Phone 73406 0
+61 (0) 3 9929 8366
Fax 73406 0
+61 (0) 3 9663 1958
Email 73406 0
[email protected]
Contact person for public queries
Name 73407 0
Katie Davis
Address 73407 0
Dept. of Otolaryngology
The University of Melbourne, Victoria, Australia
Royal Victorian Eye & Ear Hospital
Level 5, 32 Gisborne St, East Melbourne, 3002
Country 73407 0
Australia
Phone 73407 0
+61 3 9929 8293
Fax 73407 0
+61 3 9929 8293
Email 73407 0
[email protected]
Contact person for scientific queries
Name 73408 0
Katie Davis
Address 73408 0
Dept. of Otolaryngology
The University of Melbourne, Victoria, Australia
Royal Victorian Eye & Ear Hospital
Level 5, 32 Gisborne St, East Melbourne, 3002
Country 73408 0
Australia
Phone 73408 0
+61 3 9929 8293
Fax 73408 0
+61 3 9929 8293
Email 73408 0
[email protected]

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