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

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

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.

Cisplatin is a widely used and effective chemotherapy in the treatment of adult and pediatric solid tumors, including bladder, testicular, head and neck, and lung cancers. Serious side effects of cisplatin treatment include ototoxicity. To date, no approved therapy to prevent or treat ototoxicity exists for people receiving cisplatin treatment, which remains the most common dose-limiting side effect associated with cisplatin administration.

Participants who will be undergoing cancer treatment with high doses of cisplatin every 21 or 28 days will receive IT injection with one ear receiving DB-020 and one ear receiving placebo during each administration. The study will comprise 2 parts. In Part A, eligible participants will be randomized to one of two doses of DB-020. In Part B, participants will be treated with a single dose of DB-020, as selected from data collected in Part A. In both Parts A and B, the ear receiving DB-020 or placebo will be randomized. The choice of dose in Part B will depend on the data from Part A. If appropriate safety and efficacy is observed at either dose level, the Sponsor has the option of dosing at one of these concentrations either unilaterally (ie, with placebo administered in the contralateral ear) or bilaterally (ie, open-label DB-020 administered to both ears) in Part B.

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.

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