Clinical trial NCT03116113: A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: X-Linked Retinitis Pigmentosa
Keywords: XLRP
Ophthalmology
Gene Therapy
Retinitis Pigmentosa GTPase Regulator (RPGR)
AAV8
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-04-14
Enrollment: 50
Sex: MALE
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.

Eligibility criteria: Key Inclusion Criteria:

Part 1:

* Participants with genetically confirmed diagnosis of XLRP (with RPGR mutation).
* Participant with active disease clinically visible within the macular region in both eyes.

Part 2:

- Participant with mean total retinal sensitivity in the study eye as assessed by microperimetry ≥ 0.1 dB and ≤8 dB.

Key exclusion Criteria:

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.

Primary outcomes:
measure: Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to Month 24
measure: Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 0 (surgery) in Part 1 of the study up to 24 months
measure: 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
timeFrame: Month 12
measure: Part 2: Number of Participants With TEAEs
timeFrame: Day 0 (surgery) in Part 2 of the study up to 12 months
Secondary outcomes:
measure: 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
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: 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
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points Assessed by MAIA Microperimetry
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points Assessed by MAIA Microperimetry
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Mean Best Corrected Visual Acuity (BCVA) Reported as Letters
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Mean Low Luminance Visual Acuity (LLVA) Reported as Letters
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for BCVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for LLVA
timeFrame: Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Central Ellipsoid Area
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Central Horizontal Ellipsoid Width
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Total Area of Preserved Autofluoroscence
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Distance From Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence
timeFrame: Baseline, Months 1, 3, 6, 9, 12, 18, and 24
measure: Part 1: Change From Baseline in Mean Volume of 30-Degree Hill of Vision
timeFrame: Baseline, Months 6, 12, and 24
measure: Part 1: Change From Baseline in Mean Volume of Full Field Hill of Vision
timeFrame: Baseline, Months 6, 12, and 24
measure: Part 1: Change From Baseline in Contrast Sensitivity (CS) Score
timeFrame: Baseline, Months 3, 6, 12, and 24
measure: 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
timeFrame: Months 1, 2, 3, 6, and 9
measure: 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
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry
timeFrame: Baseline, Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry
timeFrame: Baseline, Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Change From Baseline in BCVA Reported as Letters
timeFrame: Baseline, Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Change From Baseline in Mean LLVA Reported as Letters
timeFrame: Baseline, Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for BCVA
timeFrame: Months 1, 2, 3, 6, 9, and 12
measure: Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for LLVA
timeFrame: Months 1, 3, 6, 9, and 12
measure: Part 2: Change From Baseline in Volume of 30-Degree Hill of Vision Assessed by Octopus 900
timeFrame: Baseline, Months 3, 6, and 12
measure: Part 2: Change From Baseline in Volume of Full Field Hill of Vision Assessed by Octopus 900
timeFrame: Baseline, Months 3, 6, and 12
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, Nanda A, Davies A, Wood LJ, Salvetti AP, Fischer MD, Aylward JW, Barnard AR, Jolly JK, Luo E, Lujan BJ, Ong T, Girach A, Black GCM, Gregori NZ, Davis JL, Rosa PR, Lotery AJ, Lam BL, Stanga PE, MacLaren RE. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020 Mar;26(3):354-359. doi: 10.1038/s41591-020-0763-1. Epub 2020 Feb 24.