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Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset
- Source :
- Ophthalmology: Journal of The American Academy of Ophthalmology, Ophthalmology: Journal of The American Academy of Ophthalmology, Elsevier, 2021, 128 (5), pp.649-660. ⟨10.1016/j.ophtha.2020.12.012⟩, Ophthalmology 128(5), 649-660 (2021). doi:10.1016/j.ophtha.2020.12.012
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- International audience; Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included.Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye.Main outcome measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96.Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively.Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes.
- Subjects :
- Male
Time Factors
Visual acuity
genetic structures
physiology [Visual Fields]
[SDV]Life Sciences [q-bio]
efficacy
Visual Acuity
Phases of clinical research
genetics [Dependovirus]
chemistry.chemical_compound
0302 clinical medicine
Visual Field Test
Quality of life
Clinical endpoint
Contrast (vision)
intravitreal gene therapy
media_common
0303 health sciences
physiology [Visual Acuity]
Diabetic retinopathy
Dependovirus
Middle Aged
Dependoviru
genetics [DNA, Mitochondrial]
Phase 3 randomized double-masked clinical trial
Treatment Outcome
Intravitreal Injections
diagnosis [Optic Atrophy, Hereditary, Leber]
Female
Genetic Vector
medicine.symptom
Human
Adult
safety
LEBER HEREDITARY OPTIC NEUROPATHY
medicine.medical_specialty
retinal anatomic measures
Time Factor
Adolescent
media_common.quotation_subject
psychology [Optic Atrophy, Hereditary, Leber]
Genetic Vectors
Visual Field
Humphrey visual field perimetry
Optic Atrophy, Hereditary, Leber
therapy [Optic Atrophy, Hereditary, Leber]
DNA, Mitochondrial
bilateral visual improvement
Follow-Up Studie
Leber Hereditary Optic Neuropathy
Young Adult
03 medical and health sciences
Double-Blind Method
Ophthalmology
psychology [Quality of Life]
Electroretinography
medicine
Humans
ddc:610
Aged
030304 developmental biology
contrast sensitivity
business.industry
Intravitreal Injection
Retinal
Genetic Therapy
retinal anatomic measure
medicine.disease
eye diseases
genetics [Optic Atrophy, Hereditary, Leber]
chemistry
Mutation
030221 ophthalmology & optometry
Visual Field Tests
sense organs
Visual Fields
business
Follow-Up Studies
best-corrected visual acuity
Subjects
Details
- Language :
- English
- ISSN :
- 01616420
- Database :
- OpenAIRE
- Journal :
- Ophthalmology: Journal of The American Academy of Ophthalmology, Ophthalmology: Journal of The American Academy of Ophthalmology, Elsevier, 2021, 128 (5), pp.649-660. ⟨10.1016/j.ophtha.2020.12.012⟩, Ophthalmology 128(5), 649-660 (2021). doi:10.1016/j.ophtha.2020.12.012
- Accession number :
- edsair.doi.dedup.....61639fdbd5cf15223e6676350bc8de96
- Full Text :
- https://doi.org/10.1016/j.ophtha.2020.12.012⟩