A First-In-Human, Open Label, Dose Escalation Trial to Evaluate the Safety, Tolerability and Pharmacodynamics of a Single Dose of AXV-101 in Patients With Bardet-Biedl Syndrome 1 (BBS1) Bi-Allelic Mutations and Retinal Degeneration
概览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- Axovia Therapeutics
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To evaluate the preliminary safety and tolerability of AXV-101 in participants with BBS1
概览
简要总结
The goal of this first in human study is to evaluate the preliminary safety and tolerability of AXV-101 in participants with BBS1. The main questions it aims to answer are:
- Is AXV-101 safe and tolerable to use in participants with BBS1?
- To determine the therapeutic dose of AXV-101 in participants with BBS1
- To investigate the concentration of AXV-101 in blood, urine and tears (both eyes)
Participants will undergo comprehensive ophthalmic assessments to evaluate functional and structural changes from baseline to one year in the treated eye compared with the untreated eye. Additional evaluations will include blood, urine, and tear testing for safety and pharmacokinetics, and quality of life questionnaires completed by both participants and caregivers. Safety will also be assessed by monitoring the frequency and severity of adverse events, including serious adverse events, through medical history, physical examinations, and laboratory testing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate in this trial, an individual must meet all the following criteria:
- •Male or female participants aged 4 to 17 years (inclusive).
- •Able to provide written informed consent:
- •Parent(s)/guardian(s) prior to the initiation of any study-specific procedures for participants who are under the age of 18 2.
- •Participants aged 6-17 years of age may (according to the judgement of the investigator) provide their written assent; consent will also be required from the legal guardian of the participant.
- •Participants aged below 6 years of age will not be required to sign an assent form; however, their views should be considered; consent will be required from the legal guardian of the participant.
- •Participant with a confirmed diagnosis of bi-allelic BBS1 mutations. Molecular diagnosis/genetic testing will have been undertaken by an accredited laboratory using an assay that has the relevant mark of conformity and is used as per its intended use. UK diagnostic genetic laboratories must conform to the Association for Clinical Genomic Science (ACGS) and adopt the ACMG guidelines for the determination of pathogenicity. US diagnostic genetic laboratories must be CLIA-approved.
- •Participants with presentation of retinal degeneration (evidence of early Rod-Cone Dystrophy, Cone-Rod Dystrophy or Night vision loss \[nyctalopia\])
- •Participants with sufficient viable retinal cells as determined by OCT. Participants must have either:
- •A measurable area of intact ellipsoid within the posterior pole - minimum 1500 microns horizontal width 5.
排除标准
- 未提供
研究组 & 干预措施
Cohort 1
Cohort 1 will include up to three participants. Participants in this cohort will be administered a minimally effective dose of AXV-101 (3 E11 Viral genomes; Vg). The safety data for the first participant will be reviewed by an Independent Data Monitoring Committee (IDMC) before the next participants are enrolled. The IDMC will then review the next two participants' data before opening the next part of the study (Cohort 2).
干预措施: AXV-101 (Genetic)
Cohort 2
Cohort 2 will include up to nine participants. Participants in this cohort will be administered a therapeutic dose of AXV-101 (5 E11 Vg). The IDMC will review the safety data after each dose for the first three participants, and if no safety concerns are raised, the remaining six participants in cohort 2 will be dosed sequentially.
干预措施: AXV-101 (Genetic)
结局指标
主要结局
To evaluate the preliminary safety and tolerability of AXV-101 in participants with BBS1
时间窗: Through study completion, 5 years
Evaluation will be via frequency and severity of all adverse events (AEs) including serious adverse events (SAEs) and their relationship to AXV-101 throughout the study (5 years)
次要结局
- To determine the therapeutic dose of AXV-101 in young participants with BBS1(Change from baseline through 1 year)
- To investigate the concentration of AXV-101 in blood, urine and tears (both eyes)(From screening to Day 35)