An Open-Label, Dose Escalation and Double-Masked, Randomized, Controlled Study to Evaluate the Safety and Tolerability of Sepofarsen in Pediatric Subjects <8 Years of Age With Leber Congenital Amaurosis Type 10 (LCA10) Due to the c.2991 +1655A>G (p.Cys998X) Mutation.
试验速览
- 阶段
- 2 期
- 入组人数
- 15
- 试验地点
- 9
- 主要终点
- Incidence and severity of ocular adverse events (AEs)
研究概览
简要总结
PQ-110-005 (BRIGHTEN) is an open-label, dose escalation and double-masked, randomized, controlled study evaluating safety and tolerability of sepofarsen administered via intravitreal (IVT) injection in pediatric subjects (<8 years of age) with LCA10 due to the c.2991+1655A>G mutation over 24 months of treatment.
详细描述
This is an open-label, dose escalation and double-masked, randomized, controlled study evaluating safety and tolerability of sepofarsen administered via intravitreal (IVT) injection in pediatric subjects (<8 years of age) with LCA10 due to the c.2991+1655A>G mutation. The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
In the open label part; subjects will be assigned to one of 3 planned dose groups using a staggered dose escalation design. After at least 1 patient is dosed in each group; the Data Monitoring Committee (DMC) will review at least 4 weeks of safety data post dosing; and may recommend initiation of the next dose group. The DMC may recommend initiation of the double-masked randomized part of the study after completion of the last dose group in the dose escalation part of the study.
In the double-masked, randomized, controlled part of the study; subjects will be randomized to one of 2 planned dose groups .
Subjects will receive a unilateral IVT injection of sepofarsen on Day 1. Thereafter a 6-monthly dosing schedule is planned.
After each dosing subjects will be assessed for safety and tolerability at follow up visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 0 Years 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female child, <8 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. A historic genotyping report from a certified laboratory are acceptable with Sponsor approval.
- •BCVA equal to or better than Logarithm of the Minimum Angle of Resolution (logMAR) + 4.0 (Light Perception), and equal to or worse than logMAR + 0.4 in the treatment eye.
- •Detectable outer nuclear layer (ONL) in the area of the macula.
排除标准
- •Presence of any significant ocular or non-ocular disease/disorder which may put the subject at risk because of participation in the trial' may influence the results of the trial, or the subject's ability to participate in the trial.
- •Receipt within 1 month prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the trial.
- •Current treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to cytostatics, interferons, TNF-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system).
- •Current treatment or treatment within the past 3 months or planned treatment with drugs known to be toxic to the lens, retina, or the optic nerve.
- •Use of any investigational drug or device within 3 months or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the trial period.
- •Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.
研究组 & 干预措施
Group 1 - open label
干预措施: sepofarsen (Drug)
Group 2 - open label
干预措施: sepofarsen (Drug)
Group 3: open label
干预措施: sepofarsen (Drug)
Group 4: double-masked, randomized to one of 2 dose cohorts
干预措施: sepofarsen (Drug)
结局指标
主要结局
Incidence and severity of ocular adverse events (AEs)
时间窗: 24 months
Incidence and severity of ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs)
时间窗: 24 months
Incidence and severity of non-ocular adverse events (AEs)
次要结局
- Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)(12 months)
- Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)(12 months)