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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04262336




Registration number
NCT04262336
Ethics application status
Date submitted
29/01/2020
Date registered
10/02/2020
Date last updated
21/07/2020

Titles & IDs
Public title
Study to Evaluate Safety and Efficacy of DB-020 to Protect Hearing in Patients Receiving Cisplatin for Cancer Treatment
Scientific title
Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Doses of DB-020 in Patients Receiving Cisplatin
Secondary ID [1] 0 0
1111-1243-8337
Secondary ID [2] 0 0
DB-020-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ototoxicity 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DB-020
Treatment: Drugs - Placebo

Active Comparator: DB-020 for Injection, 12%/placebo - dosage

Active Comparator: DB-020 for Injection, 25%/placebo - dosage


Treatment: Drugs: DB-020
Injectable sterile viscous solution of DB-020 and sodium hyaluronate in sterile water

Treatment: Drugs: Placebo
Injectable sterile viscous solution of sodium hyaluronate in sodium chloride

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients with treatment-emergent Adverse Events (TEAEs) and/or abnormal changes from baseline in clinical laboratory abnormalities and/or vital signs and/or ECG assessments - To investigate the safety and tolerability of DB-020 when given intratympanically to patients receiving cisplatin chemotherapy treatment
Timepoint [1] 0 0
From screening/baseline (Day -28 to Day -2) or day of first dose of DB-020 (Cycle 1 Day 1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [1] 0 0
Incidence of Ototoxicity measured by American Speech-Language-Hearing Association (ASHA) criteria - Air conduction audiometry consists of a set of pure tones presented to the patient through small speakers in a headset, played at carrier frequencies ranging from 250 to 16,000 Hz. Pure tone thresholds are recorded for each frequency tested. Ototoxicity will be defined according to the American Speech-Language-Hearing Association (ASHA) criteria for significant ototoxic change. Significant ototoxic change must meet one of the following three criteria: (i) =20 dB decrease at any one test frequency, (ii) =10 dB decrease at any two adjacent frequencies, or (iii) loss of response at three consecutive frequencies where responses were previously obtained. The presence of ototoxicity will be calculated for each ear
Timepoint [1] 0 0
Baseline (Day -5 to Day -1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [2] 0 0
Changes from Baseline in Pure Tone Threshold Values compared to End of Treatment [Changes in Hearing] - Air conduction audiometry consists of a set of pure tones presented to the patient through small speakers in a headset, played at carrier frequencies ranging from 250 to 16,000 Hz. Pure tone thresholds are recorded for each frequency tested. Higher values indicate a greater degree of hearing impairment. Changes from baseline values will be calculated for each frequency and ear as the reported pure tone threshold value minus the baseline value. A negative change from baseline indicates hearing loss
Timepoint [2] 0 0
Baseline (Day -5 to Day -1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [3] 0 0
Changes from Baseline in Tinnitus Functional Index (TFI) Total Score compared to End of Treatment [Changes in Hearing] - The TFI is a 25-item self-assessment scale comprised of eight subscales (intrusiveness, sense of control, cognitive, sleep, auditory, relaxation, quality of life, and emotional) measuring the impact of tinnitus. Items are scored on a range of 0 to 10. The TFI Total Score is calculated as the mean of the 25 individual item scores multiplied by 10. The Total Score can range from 0 to 100. Higher scores indicate a greater degree of tinnitus-related impairment. Change from baseline values will be calculated as the reported TFI value minus the baseline value. A positive change from baseline indicates more tinnitus-related impairment
Timepoint [3] 0 0
Baseline (Day -5 to Day -1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [4] 0 0
Changes from Baseline in Distortion Product Otoacoustic Emission (DPOAE) Values compared to End of Treatment [Changes in Hearing] - Distortion product otoacoustic emission (DPOAE) is defined as sound generated within the cochlea by stimulating the ear with two simultaneous tones of different frequency. DPOAEs serve as an objective measure of hearing sensitivity. Tones will be played from low to high frequencies (1 to 4 kHz) at soft to moderate levels to assess responses at different regions of the inner ear. DP levels will be recorded for each frequency and ear. Higher DP levels indicate more sensitive hearing. Change from baseline values will be calculated as the reported DP level value minus the baseline value. A negative change from baseline indicates less sensitive hearing
Timepoint [4] 0 0
Baseline (Day -5 to Day -1) and Cycle 1 Day 1 (21 or 28 day cycles) and End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [5] 0 0
Changes from Baseline in Words-in-Noise (WIN) Values compared to End of Treatment [Changes in Hearing] - The WIN test is a series of trials to measure the ability to accurately recognize speech in noise. In each trial, a series of 5 words is read to the listener with the instruction to repeat each word. The number of correct responses is captured. Trials are presented at 7 signal-to-noise ratios, from 0 to 24 dB, in steps of 4 dB. WIN thresholds are then calculated for each ear using the Spearman-Kaerber method. Higher WIN thresholds indicate better word recognition. Change from baseline values will be calculated for each ear as the reported WIN threshold value minus the baseline value. A negative change from baseline indicates worse word recognition
Timepoint [5] 0 0
Baseline (Day -5 to Day -1) and Cycle 1 Day 1 (21 or 28 day cycles) and End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [6] 0 0
Changes from Baseline in Hearing Handicap Inventory for Adults (HHIA) Total Score compared to End of Treatment [Changes in Hearing] - The Hearing Handicap Inventory for Adults (HHIA) is a 25-item self-assessment scale comprised of two subscales (emotional and social/situational) measuring the impact of hearing loss. Items are scored on a range of 0 to 4. The HHIA Total Score is calculated as the sum of the 25 individual item scores. The HHIA Total Score can range from 0 to 100. Higher scores indicate a greater degree of hearing impairment. Change from baseline values will be calculated as the reported HHIA value minus the baseline value. A positive change from baseline indicates more hearing impairment
Timepoint [6] 0 0
Baseline (Day -5 to Day -1) and Cycle 1 Day 1 (21 or 28 day cycles) and End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug
Secondary outcome [7] 0 0
Plasma Concentrations of DB-020
Timepoint [7] 0 0
Predose and 0.25 hours prior to cisplatin administration on Cycle 1 Day 1 (21 or 28 day cycles)
Secondary outcome [8] 0 0
Maximum observed plasma concentration (Cmax) of free (unbound) cisplatin
Timepoint [8] 0 0
0.25 hours predose, mid-point of IV infusion, end of infusion, 0.25, 0.5, 1 & 2 hours postdose on Day 1 of each cycle (21 or 28 day cycles)
Secondary outcome [9] 0 0
Area under the plasma concentration-time curve (AUC 0-inf) of free (unbound) cisplatin
Timepoint [9] 0 0
0.25 hours predose, mid-point of IV infusion, end of infusion, 0.25, 0.5, 1 & 2 hours postdose on Day 1 of each cycle (21 or 28 day cycles)
Secondary outcome [10] 0 0
Time to reach maximum observed plasma concentration (tmax) of free (unbound) cisplatin
Timepoint [10] 0 0
0.25 hours predose, mid-point of IV infusion, end of infusion, 0.25, 0.5, 1 & 2 hours postdose on Day 1 of each cycle (21 or 28 day cycles)
Secondary outcome [11] 0 0
Half-life (t1/2) of plasma concentrations of free (unbound) cisplatin
Timepoint [11] 0 0
0.25 hours predose, mid-point of IV infusion, end of infusion, 0.25, 0.5, 1 & 2 hours postdose on Day 1 of each cycle (21 or 28 day cycles)

Eligibility
Key inclusion criteria
- Ability to communicate with medical team and staff, willingness to participate in the
study, give written informed consent, comply with the study restrictions

- Adults aged 18 years, inclusive, or older

- Treatment for cancer with Intervenous cisplatin once every 21 or 28 days

- Plan to receive a minimum cumulative dose of cisplatin of = 280 mg/m2 over at least
three cycles

- Concomitant use of other chemotherapy and radiation is permitted except
investigational agents and/or radiation > 35 Grays involving the cochlear area

- Male patients, their female partner(s), and female patients 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 the last study drug administration.

- Male and female patients who consider themselves abstinent, and who agree to remain
abstinent during the study and for 90 days after the last study drug administration

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Anticipated survival > 1 year

- Normal or not clinically significant otoscopic findings in both ears

- Patient has read, understood, and voluntarily signed the informed consent form.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Female or male patients with female partners who are pregnant, lactating, or planning
to attempt to become pregnant during this study or within 90 days after last dose of
study drug

- Prior treatment with a cisplatin regimen

- Signs of disturbed integrity of the tympanic membrane on otoscopy or tympanometry

- History of congenital hearing loss

- History of otological surgery (excluding myringotomy tubes or simple tympanoplasty)

- History of sudden hearing loss

- History of conductive hearing loss > 10 decibels at 2 frequencies in either ear

- Diagnosis of Meniere's disease

- Diagnosis of autoimmune middle ear disease

- Hearing loss greater than (not including) 45 decibels Hearing Loss averaged at 6 and 8
kilohertz in either ear

- Asymmetry in hearing thresholds between left and right ear equal to or exceeding 20
decibels at any single frequency or 10 decibels at any 3 consecutive frequencies, up
to and including 8 kilohertz

- Previous radiation exposure > 35 Grays to all or part of the cochlea

- Consumption of > 6 grams of salicylate or > 5 grams of acetaminophen (paracetamol) per
day for the past month, or aminoglycoside use in the past month

- Use of any investigational drug or device within 30 days prior to the first dose of
study medication (6 months for biologic therapies) or 5 half-lives of the
investigational drug, if known, whichever time is longer

- History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) and/or
allergy to the excipients of the study medications

- Presence of hepatitis C antibody with reflex hepatitis C virus (HCV) RNA testing (if
anti-HCV is positive), hepatitis B surface antigen, or HIV antibodies 1 and 2

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)
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
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
The Crown Princess Mary Cancer Care Centre - Westmead
Recruitment hospital [2] 0 0
Queensland Head and Neck Cancer Centre - Woolloongabba
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Oncology and Palliative Care Research - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Montana
Country [7] 0 0
United States of America
State/province [7] 0 0
West Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Decibel Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate whether DB-020 administered via an injection in the
middle ear prevents hearing loss in participants who will receive high doses of cisplatin as
part of their treatment for cancer.
Trial website
https://clinicaltrials.gov/show/NCT04262336
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Keilty, MS
Address 0 0
Decibel Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Heather Wolff, BA
Address 0 0
Country 0 0
Phone 0 0
(617) 370-8701
Fax 0 0
Email 0 0
hwolff@decibeltx.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04262336