Study to Evaluate Safety and Efficacy of DB-020 to Protect Hearing in Patients Receiving Cisplatin for Cancer Treatment

NCT04262336 | Completed Phase 1 FDA Drug

• 2 other identifiers: DB-020-0021111-1243-8337
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 8

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.

Conditions

Ototoxicity

Keywords

Ototoxicity; Hearing loss; Chemotherapy-induced

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (11)

• Incidence of Ototoxicity measured by American Speech-Language-Hearing Association (ASHA) criteria

  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

• Changes from Baseline in Pure Tone Threshold Values compared to End of Treatment [Changes in Hearing]

  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

• Changes from Baseline in Tinnitus Functional Index (TFI) Total Score compared to End of Treatment [Changes in Hearing]

  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

• Changes from Baseline in Distortion Product Otoacoustic Emission (DPOAE) Values compared to End of Treatment [Changes in Hearing]

  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

• Changes from Baseline in Words-in-Noise (WIN) Values compared to End of Treatment [Changes in Hearing]

  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

Study Arms (2)

DB-020 for Injection, 12%/placebo

ACTIVE COMPARATOR

dosage

Drug: DB-020; Drug: Placebo

DB-020 for Injection, 25%/placebo

ACTIVE COMPARATOR

dosage

Drug: DB-020; Drug: Placebo

Interventions

DB-020 DRUG

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

Also known as: Sodium Thiosulfate (STS) pentahydrate formulated in sodium hyaluronate

DB-020 for Injection, 12%/placebo; DB-020 for Injection, 25%/placebo

Placebo DRUG

Injectable sterile viscous solution of sodium hyaluronate in sodium chloride

Also known as: sodium hyaluronate in sodium chloride

DB-020 for Injection, 12%/placebo; DB-020 for Injection, 25%/placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Decibel Therapeutics: lead

Study Sites (8)

University of Miami Health System

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Northwell Health Cancer Center

Lake Success, New York, 11042, United States

Location

WVU Cancer Institute

Morgantown, West Virginia, 26506, United States

Location

Queensland Head and Neck Cancer Centre

Woolloongabba, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Oncology and Palliative Care Research

Melbourne, Victoria, 3065, Australia

Location

Fiona Stanley Hospital, Clinical Trials Unit Cancer Center

Murdoch, Western Australia, 6150, Australia

Location

MeSH Terms

Conditions

Ototoxicity; Hearing Loss

Interventions

sodium thiosulfate; Hyaluronic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Hearing Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Pablo LaPuerta

  Decibel Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: DB-020 12% right ear/placebo left ear; DB-020 12% left ear/placebo right ear; DB-020 25% right ear/placebo left ear; DB-020 25% left ear/placebo right ear on Day 1 of every 21 or 28 day cisplatin cycle for up to 6 cycles until cisplatin administration is discontinued Part B: DB-020 12% both ears or DB-020-25% both ears on Day 1 of every 21 or 28 day cisplatin cycle for up to 6 cycles until cisplatin administration is discontinued

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 10, 2020
• Study Start: February 21, 2020
• Primary Completion: July 30, 2022
• Study Completion: May 23, 2023
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (4)