NCT05788536招募中1 期
A Phase 1/2, Open-Label, Multicenter Trial With a Single Ascending Dose Cohort With Unilateral Intracochlear Injection Followed by a Bilateral Injection Expansion Cohort to Evaluate the Safety, Tolerability, and Efficacy of DB-OTO in Children and Infants With Biallelic hOTOF Mutations
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 26
- 主要终点
- Incidence and severity of treatment-emergent adverse events
研究概览
简要总结
Regeneron is conducting a study of an investigational new drug called DB-OTO. DB-OTO is a gene therapy that is being developed to treat pediatric and adult participants who have severe-to profound and profound hearing loss due to changes in the otoferlin gene.
The purpose of this study is to:
- Learn about the safety of DB-OTO
- Determine how well DB-OTO is tolerated (does not cause ongoing discomfort)
- Evaluate the efficacy of DB-OTO (how well DB-OTO works)
详细描述
Former Sponsor Decibel Therapeutics
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
- •Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
- •Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
- •Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
- •Presence of biallelic, likely pathogenic or pathogenic OTOF variants
- •No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
- •Audiological Criteria:
- •Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; >90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
- •Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants >24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
- •No evidence from measures of hearing loss that show a dependence on body temperature
- •From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration.
排除标准
- •History of prior treatment with gene therapy
- •Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography [CT] or Magnetic Resonance Imaging [MRI]) in the ear(s) to be infused with DB-OTO
- •History or presence of other permanent or untreatable hearing loss conditions
- •Prior or current history of malignancies
- •Prior or current history of meningitis
- •History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
- •History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol
- •Note: Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
DB-OTO - Part C
Experimental
Unilateral or bilateral intracochlear dosing
干预措施: DB-OTO (Genetic)
DB-OTO - Part B
Experimental
Bilateral intracochlear dosing using the dose selected based on safety and efficacy data from Part A
干预措施: DB-OTO (Genetic)
DB-OTO - Part A
Experimental
Unilateral intracochlear dosing
干预措施: DB-OTO (Genetic)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events
时间窗: Up to week 48
Achievement of a hearing sensitivity threshold of ≤70 dB assessed by average pure tone audiometry (PTA)
时间窗: Up to week 48
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to week 104
Achievement of a hearing sensitivity threshold of ≤70 dB assessed by average Pure Tone Audiometry (PTA)
时间窗: Up to week 104
次要结局
- Auditory Brainstem Response (ABR) to click(Up to week 48)
- Achievement of hearing sensitivity threshold of ≤25 dB assessed by average PTA(Up to week 48)
- Achievement of a hearing sensitivity threshold of ≤45 dB assessed by average PTA(Up to week 48)
- Speech Reception Threshold (SRT): achievement of a threshold of ≤70 dB(Up to week 48)
- SRT: achievement of a threshold of ≤45 dB(Up to week 48)
- SRT: achievement of a threshold of ≤25 dB(Up to week 48)
- Severity in speech perception ability assessed by Global Impression scales, determined by clinician(Up to week 48)
- Severity in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian(Up to week 48)
- Change in speech perception ability assessed by Global Impression scales, determined by clinician(Up to week 48)
- Change in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian(Up to week 48)
- Average PTA threshold in the subset of patients who achieved an average PTA threshold ≤70 dB(Up to week 48)
- Average PTA threshold in the subset of patients who achieved an average PTA threshold >70 dB but ≤85 dB(Up to week 48)
- Speech perception scores by age-appropriate tests(Up to week 48)
- Achievement of a hearing sensitivity threshold improvement of ≥10 dB from baseline(Up to week 48)
- Time to an average PTA threshold ≤70 dB(Up to week 48)
- Incidence of patients who regress to >70 dB after having achieved average PTA threshold ≤70 dB(Up to week 48)
- Persistence of an average PTA threshold ≤70 dB(Up to week 48)
- Achievement of a score ≥3 on the Early Speech Perception (ESP) test(At week 104)
- Achievement of hearing sensitivity threshold of ≤45 dB assessed by average PTA(Up to week 104)
- Achievement of hearing sensitivity threshold of ≤25 dB assessed by average PTA(Up to week 104)
- Achievement of a score of 4 on the ESP test(At week 104)
- Speech Awareness Threshold (SAT): achievement of a threshold of ≤70 dB(Up to week 104)
- SAT: achievement of a threshold of ≤45 dB(Up to week 104)
- SAT: achievement of threshold of ≤25 dB(Up to week 104)
- Average PTA threshold in the subset of patients who achieved an average PTA threshold ≤70 dB(Up to week 104)
- Time to an average PTA threshold ≤70 dB(Up to week 104)
- Persistence of an average PTA threshold ≤70 dB(Up to week 104)
- Incidence of patients who regress to >70 dB after having achieved average PTA threshold(Up to week 104)
- Severity in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)(Up to week 48)
- Change in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)(Up to week 48)
- Presence of auditory brainstem response (ABR) to click at ≤90 dB normalized Hearing Level (nHL)(At week 104)
- Speech perception scores by age-appropriate tests (other than ESP)(At week 104)
- Severity in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)(At week 104)
- Change in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)(At week 104)
- Change from baseline on LittlEARS®(At week 104)
- Change in scores on LittlEARS®(At week 104)
- Change from baseline on Auditory Skills Checklist(At week 104)
- Change in scores on Auditory Skills Checklist(At week 104)
- Change from baseline on MacArthur-Bates Communicative Development Inventories (MB-CDI)-Words and Gestures(At week 104)
- Change in scores on MB-CDI-Words and Gestures(At week 104)
- Change from baseline on MB-CDI -Words and Sentences(At week 104)
- Change in scores on MB-CDI -Words and Sentences(At week 104)
- Change from baseline on MB-CDI-III Vocabulary and Grammar(At week 104)
- Change in scores on MB-CDI-III Vocabulary and Grammar(At week 104)
- Clinical assessments of speech production: articulation(At week 104)
- Clinical assessments of speech production: speech intelligibility(At week 104)
- Speech Awareness Threshold (SAT): achievement of a threshold of ≤70 dB(Up to week 48)
- SAT: achievement of a threshold of ≤45 dB(Up to week 48)
- SAT: achievement of threshold of ≤25 dB(Up to week 48)
- Change in scores on MB-CDI(At week 104)
- Change from baseline on MacArthur-Bates Communicative Development Inventories (MB-CDI)(At week 104)
- Auditory Brainstem Response (ABR) to click stimulus at ≤90 dB normalized Hearing Level (nHL)(Up to week 48)
- Speech perception scores by age-appropriate tests(Up to week 104)
- Average PTA threshold in the subset of participants who achieved an average PTA threshold ≤70 dB(Up to week 104)
- Average PTA threshold in the subset of participants who achieved an average PTA threshold >70 dB but ≤85 dB(Up to week 48)
- Achievement of a hearing sensitivity threshold improvement of ≤85 dB HL, as assessed by PTA(Up to week 48)
- Incidence of participants who regress to >70 dB after having achieved average PTA threshold(Up to week 104)
- Presence of ABR to click at ≤90 dB nHL(At week 104)
研究者
研究点 (26)
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