A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- Part 2: Percentage of Study Eyes With ≥7 Decibels (dB) Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry
研究概览
简要总结
The objective of the study is to evaluate the safety, tolerability and efficacy of a single sub-retinal injection of BIIB112 in participants with X-linked retinitis pigmentosa (XLRP).
详细描述
This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participants with genetically confirmed diagnosis of XLRP (with RPGR mutation).
- •Participant with active disease clinically visible within the macular region in both eyes.
- •Participant with mean total retinal sensitivity in the study eye as assessed by microperimetry ≥ 0.1 dB and ≤8 dB.
排除标准
- •Parts 1 and 2:
- •Participant with history of amblyopia in either eye.
- •Participated in a gene therapy trial previously or a clinical trial with an investigational drug in the past 12 weeks or received a gene/cell-based therapy at any time previously.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
结局指标
主要结局
Part 2: Percentage of Study Eyes With ≥7 Decibels (dB) Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry
时间窗: Month 12
MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0', or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.
Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: Up to Month 24
DLTs are defined as any of the following events considered to be related to study drug: Sustained decrease in best-corrected visual acuity (BCVA) of ≥30 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart compared to baseline (sustained is defined as lasting 48 hours or more until recovery, with recovery defined as visual acuity (VA) returning to within 10 letters of baseline VA. An exception is made for surgery-related events occurring in close temporal association {within \<24 hours} of the surgery); Vitreous inflammation, vitritis (\>Grade 3 using standardized Nussenblatt vitreous inflammation scale grading); Any clinically significant retinal damage observed that is not directly attributed to complications of surgery; Any clinically relevant suspected unexpected serious adverse reaction, with the exception of vision loss or vision threatening.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Day 0 (surgery) in Part 1 of the study up to 24 months
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as the AEs starting or worsening on or after the day of the first surgery.
Part 2: Number of Participants With TEAEs
时间窗: Day 0 (surgery) in Part 2 of the study up to 12 months
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as AEs starting on or after the day of the first surgery.
次要结局
- Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points Assessed by MAIA Microperimetry(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Best Corrected Visual Acuity (BCVA) Reported as Letters(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points Assessed by MAIA Microperimetry(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Low Luminance Visual Acuity (LLVA) Reported as Letters(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Volume of Full Field Hill of Vision(Baseline, Months 6, 12, and 24)
- Part 2: Change From Baseline in BCVA Reported as Letters(Baseline, Months 1, 2, 3, 6, 9, and 12)
- Part 2: Change From Baseline in Mean LLVA Reported as Letters(Baseline, Months 1, 3, 6, 9, and 12)
- Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Central Ellipsoid Area(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Central Horizontal Ellipsoid Width(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Contrast Sensitivity (CS) Score(Baseline, Months 3, 6, 12, and 24)
- Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Change From Baseline in Volume of Full Field Hill of Vision Assessed by Octopus 900(Baseline, Months 3, 6, and 12)
- Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Months 1, 2, 3, 6, and 9)
- Part 2: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Baseline, Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for LLVA(Months 1, 3, 6, 9, and 12)
- Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for BCVA(Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Total Area of Preserved Autofluoroscence(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Distance From Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence(Baseline, Months 1, 3, 6, 9, 12, 18, and 24)
- Part 1: Change From Baseline in Mean Volume of 30-Degree Hill of Vision(Baseline, Months 6, 12, and 24)
- Part 2: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Baseline, Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA(Months 1, 2, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA(Months 1, 3, 6, 9, and 12)
- Part 2: Change From Baseline in Volume of 30-Degree Hill of Vision Assessed by Octopus 900(Baseline, Months 3, 6, and 12)