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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 8
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
DB-020 for Injection, 12%/placebo
dosage
干预措施: DB-020 (Drug)
DB-020 for Injection, 12%/placebo
dosage
干预措施: Placebo (Drug)
DB-020 for Injection, 25%/placebo
dosage
干预措施: DB-020 (Drug)
DB-020 for Injection, 25%/placebo
dosage
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: 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
To investigate the safety and tolerability of DB-020 when given intratympanically to patients receiving cisplatin chemotherapy treatment
次要结局
- 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)
- Area under the plasma concentration-time curve (AUC 0-inf) of free (unbound) cisplatin(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))
- 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 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)
- Time to reach maximum observed plasma concentration (tmax) of free (unbound) cisplatin(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))
- Changes from Baseline in Hearing Handicap Inventory for Adults (HHIA) Total Score 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)
- Plasma Concentrations of DB-020(Predose and 0.25 hours prior to cisplatin administration on Cycle 1 Day 1 (21 or 28 day cycles))
- Maximum observed plasma concentration (Cmax) of free (unbound) cisplatin(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))
- Half-life (t1/2) of plasma concentrations of free (unbound) cisplatin(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))