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Trial registered on ANZCTR


Registration number
ACTRN12618001710213
Ethics application status
Approved
Date submitted
12/10/2018
Date registered
16/10/2018
Date last updated
17/05/2019
Date data sharing statement initially provided
1/11/2018
Date results information initially provided
17/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety and pharmacokinetics of DB-020 when administered to healthy participants
Scientific title
Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single Ascending-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DB-020 in Healthy Volunteers
Secondary ID [1] 296310 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ototoxicity 310017 0
Condition category
Condition code
Ear 308773 308773 0 0
Deafness

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cohort 1: Single dose of 19 mg of DB-020, or placebo, into a single randomized ear (left or right) via intratympanic injection
Cohort 2: Single dose of 62 mg of DB-020, or placebo, into a single randomized ear (left or right) via intratympanic injection
Cohort 3: Single dose of 124 mg of DB-020, or placebo, into a single randomized ear (left or right) via intratympanic injection
Cohort 4: Single dose of 186 mg of DB-020, or placebo, into a single randomized ear (left or right) via intratympanic injection
Cohort 5: Single dose of DB-020, or placebo, into both ears via intratympanic injection, at a dose determined by results from Cohorts 1 to 4.
Intervention code [1] 312641 0
Treatment: Drugs
Comparator / control treatment
Viscous, sterile injection solution (1% sodium hyaluronate)
Control group
Placebo

Outcomes
Primary outcome [1] 307755 0
The primary objective is to evaluate the safety and tolerability of one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; monitoring of vital signs; physical examination; otological examination; cardiac telemetry; and any other clinical laboratory parameter abnormalities after a single intratympanic dosing of DB-020. Potential adverse events may include pain, vertigo, self-limiting bleeding, and tympanic membrane perforations, all of which will be assessed by onsite medical monitoring.
Timepoint [1] 307755 0
Adverse event information will be recorded from the time of informed consent until 29 days after dosing.
Secondary outcome [1] 352793 0
A secondary objective is to evaluate the plasma PK profile of DB-020 after one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. PK parameters determined are to include AUC(0-24), AUC(0-t), AUC(0-inf), C(max), t(max), and T(1/2).
Timepoint [1] 352793 0
Blood PK samples will be collected for analysis during the treatment period at: 0 (predose), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours, and 7, 14 and 28 days post-dose.
Secondary outcome [2] 352932 0
A secondary objective is to evaluate the urine PK profile of DB-020 after one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. PK parameters determined are to include AUC(0-24), AUC(0-t), AUC(0-inf), C(max), t(max), and T(1/2).
Timepoint [2] 352932 0
Urine PK samples will be collected for analysis during the treatment period from: predose, 0-3, 3-6, 6-12, and 12-24 hours postdose.

Eligibility
Key inclusion criteria
1. Ability to communicate with medical team and staff, willingness to participate in the study, willingness to give written informed consent, and willingness to comply with the study restrictions.
2. Healthy men and women aged 18 to 50 years, inclusive, at screening.
3. Weight: greater than or equal to 50.0 kg.
4. Body mass index (BMI): 18.0 to 32.0 kg/m^2, inclusive. BMI = Body weight (kg)/Height^2 (m^2)]
5. The absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic medical or psychiatric disease or pathology after a detailed medical and surgical history, a complete physical examination including vital signs measurements, 12-lead ECG, and clinical laboratory tests (hematology, serum chemistry, serology, and urinalysis).
6. All values for hematology and for clinical chemistry tests of serum and urine are within the normal range or showing no clinically relevant deviations, as judged by the Investigator, during screening and on the day of admission to the clinical facility.
7. Ability and willingness to abstain from alcohol, caffeine, and xanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, diet pills, "energy drinks") from 48 hours (2 days) before check-in until the final follow-up visit.
8. Male subjects, their female partner(s), and female subjects of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after study drug administration. Acceptable barrier forms of contraception are condom and diaphragm. Acceptable forms of contraception for this study for female partner(s) of childbearing potential and premenopausal female subjects are nonhormonal and hormonal intrauterine device (IUD), hormonal birth control pills, hormonal birth control patches, hormonal birth control injections [eg, Depo-Provera(R)], hormonal birth control implants, and NuvaRing(R). Male and female subjects who consider themselves abstinent, and who agree to remain abstinent during the study and for 90 days after study drug administration, will be eligible to participate in the study. Women of nonchildbearing potential are eligible for the study and are defined as 12 months with no menses before screening and a follicle-stimulating hormone (FSH) level greater than 40 IU/L during screening (ie, postmenopausal female subjects), or surgically sterile female subjects, eg, those having undergone total abdominal hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 6 months before screening for study participation. Surgically sterile female subjects may participate if they agree to use condoms during the study and for 90 days after study drug administration. Male subjects who have undergone a vasectomy at least 6 months before Screening and who have a documented negative sperm count (eg, medical records or single semen specimen) after the procedure are not required to use contraception.
9. Male subjects must agree to refrain from sperm donation within 90 days after study drug administration.
10. Hearing threshold of 25 dB or better in both ears as assessed with audiometry before randomization.
11. Normal otoscopic examination of both ears (absence of significant scarring of ear canal or tympanic membrane, absence of narrow ear canal preventing injection, etc.).
12. Must be willing to agree to avoid strenuous exercise, sunbathing, and contact sports for the period starting 7 days prior to check-in to the time of the final follow-up visit. Strenuous exercise includes long-distance running, weight lifting, lifting associated with moving, and similar activities, as well as physical activity to which the subject is not accustomed.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects meeting any of the following exclusion criteria are not to be randomized to study treatment:
1. Female or male subjects with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after dosing of study drug.
2. Sustained supine systolic blood pressure greater than 139 or less than 90 mm Hg and supine diastolic blood pressure greater than 89 or less than 50 mm Hg at screening or any day of admission to the clinical facility.
3. Resting heart rate less than 40 beats per minute or greater than 100 beats per minute during screening or on the day of admission to the clinical facility.
4. ECG during screening showing corrected QT interval using Fridericia correction formula (QTcF) greater than or equal to 450 msec. In addition, subjects with any other risk factors for QT/QTcF prolongation or any abnormality in the ECG that, in the opinion of the Investigator, increases the risk of participating in the study will be excluded.
5. Positive results for drugs of abuse, alcohol, or cotinine in the urine at screening or any day of admission to the clinical facility.
6. Positive screening test for hepatitis B surface antigen, hepatitis C antibody, and/or human immunodeficiency virus (HIV) antibodies.
7. Use of any medication (prescription or over-the-counter (OTC), including health supplements and herbal remedies, with the exception of acetaminophen as defined below) within 2 weeks (4 weeks for enzyme inducers including St. John’s Wort [Hypericum perforatum]) or 5 half-lives (whichever is longer) before the first dose of study drug.
8. Routine or chronic use of more than 2 g of acetaminophen daily.
9. Use of any investigational drug or device within 30 days of the first dose of study drug (6 months for biologic therapies) or 5 half-lives of the investigational drug, if known, whichever time period is longer.
10. Exposure to excessively loud noise (eg, concerts, loud noise at the workplace) within 24 to 48 hours before Day 1.
11. History of donation of more than 450 mL of blood within 60 days before dosing in the clinical research center or planned donation before 30 days have elapsed since intake of study drug. This will be verified by the subject’s hemoglobin and hematocrit values. Subjects with clinically significant abnormalities in hemoglobin/hematocrit will be excluded from the study.
12. Plasma, white blood cell, or platelet donation within 7 days of study participation and throughout the study.
13. Lack of venous access or inability to tolerate venipuncture as determined by the Investigator or designee.
14. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) and/or allergy to the excipients of the study drug.
15. Current smoker, currently using e-cigarettes, or discontinuation of smoking or use of e-cigarettes less than 45 days before the first dose of study drug.
16. History (within 3 months of Screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 g of alcohol).
17. Any major surgery within 4 weeks of study drug administration.
18. History or presence of malignancy within the past 5 years other than past history of localized or surgical removal of focal basal cell skin cancer; cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy.
19. Previous participation in the study.
20. Signs of disturbed integrity of the tympanic membrane on otoscopy or tympanometry.
21. History of congenital hearing loss, ontological surgery (excluding myringotomy tubes), tinnitus (currently experiencing tinnitus or history of tinnitus within 2 months before study enrollment), sudden hearing loss, hearing disorders other than age-related sensorineural hearing loss, Meniere’s disease, middle ear or ear canal inflammation or effusion.
22. History of middle ear surgery.
23. History of radiotherapy that encompasses all or part of the cochlea.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is the off-site pharmacist with no contact to participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e. computerized sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Statistical Analysis will be performed using SAS v9.3 (SAS Institute, Cary, USA). Statistical analysis will be performed in reference to each individual receiving treatment.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 12151 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 24320 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 300906 0
Commercial sector/Industry
Name [1] 300906 0
Decibel Therapeutics Australia Pty Ltd
Address [1] 300906 0
Floor 19, HWT Tower
40 City Road Southbank, VIC 3006
Country [1] 300906 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Decibel Therapeutics Australia Pty Ltd
Address
Floor 19, HWT Tower
40 City Road Southbank, VIC 3006
Country
Australia
Secondary sponsor category [1] 300471 0
None
Name [1] 300471 0
Address [1] 300471 0
Country [1] 300471 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301675 0
Bellberry Limited
Ethics committee address [1] 301675 0
129 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 301675 0
Australia
Date submitted for ethics approval [1] 301675 0
05/09/2018
Approval date [1] 301675 0
23/10/2018
Ethics approval number [1] 301675 0

Summary
Brief summary
This research project is being conducted to investigate the safety, tolerability, and pharmacokinetics of single ascending dose DB-020 when administered via intratympanic injection to healthy adult volunteers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87746 0
Dr Angela Molga
Address 87746 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide SA 5000, Australia
Country 87746 0
Australia
Phone 87746 0
+61 (08) 7088 7900
Fax 87746 0
Email 87746 0
angela.molga@sa.gov.au
Contact person for public queries
Name 87747 0
Ms Sheryl Harradine
Address 87747 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide SA 5000, Australia
Country 87747 0
Australia
Phone 87747 0
+61 (08) 7088 7900
Fax 87747 0
Email 87747 0
sheryl.harradine@cmax.com.au
Contact person for scientific queries
Name 87748 0
Ms Heather Wolff
Address 87748 0
1325 Boylston Street, Suite 500
Boston, MA 02215
Country 87748 0
United States of America
Phone 87748 0
+1 617 935 0539
Fax 87748 0
Email 87748 0
hwolff@decibeltx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is a Phase 1 study, only aggregate data may be posted/published.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Other
'Other' documents specified
Selected summary information may be available from the CSR.
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary