Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation (RESCUE)


GenSight Biologics

Status and phase

Phase 3


Optic, Atrophy, Hereditary, Leber


Device: Sham Intravitreal Injection
Biological: GS010

Study type


Funder types



2015-001265-11 (EudraCT Number)

Details and patient eligibility


The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less.


39 patients




15+ years old


No Healthy Volunteers

Inclusion criteria

Selection Criteria:

Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.

  1. Age 15 years or older.
  2. Onset of vision loss based on medically documented history or participant testimony, in at least one eye for ≤180 days in duration and if both eyes are affected the duration of vision loss in both eyes must be ≤180 days in duration.
  3. Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance.
  4. Female participants (if of childbearing potential) must agree to use effective methods of birth control up to 6 months after intravitreal (IVT) injection and male participants must agree to use condoms for up to 6 months after IVT injection.
  5. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
  6. Signed written informed consent.

Inclusion Criteria:

Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2).

  1. Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary Leber Hereditary Optical Neuropathy (LHON)-associated mutations (ND1 or ND6) in the participant's mitochondrial DNA.
  2. Review of all selection criteria to ensure continued compliance.
  3. Have a negative test for infection with human immunodeficiency virus.
  4. Have a negative pregnancy test for women of childbearing potential (a woman who is 2 years post-menopausal or surgically sterile is not considered to be of childbearing potential).

Exclusion criteria

Non-Selection Criteria:

Participants who meet at least one of the following criteria at the Screening Visit (Visit 1) will not be included into the study.

  1. Any known allergy or hypersensitivity to GS010 or its constituents.
  2. Contraindication to IVT injection.
  3. IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1).
  4. Previous vitrectomy in either eye.
  5. Narrow angle in either eye contra-indicating pupillary dilation.
  6. Presence of disorders of the ocular media, such as the cornea and lens, which may interfere with visual acuity and other ocular assessments during the study period.
  7. Vision disorders, other than LHON, involving visual disability or with the potential to cause further vision loss during the trial period.
  8. Causes of optic neuropathy other than LHON and glaucoma.
  9. Participants with known mutations of other genes involved in pathological retinal or optic nerve conditions.
  10. Presence of ocular or systemic disease, other than LHON, whose pathology or associated treatments might affect the retina or the optic nerve.
  11. History of amblyopia associated with a Snellen visual acuity equivalent of worse than 20/80 (equivalent to 6/24 at 6 meters, decimal acuity 0.25, LogMAR +0.6) in the affected eye.
  12. Presence of ocular conditions, which in the opinion of the Investigator will prevent good quality SD-OCT imaging from being obtained.
  13. Presence, in either eye, of uncontrolled glaucoma, defined as an intra-ocular pressure (IOP) greater than 25 mmHg, despite maximal medical therapy with IOP-lowering agents.
  14. Active ocular inflammation or history of idiopathic or autoimmune-associated uveitis.
  15. Participants participating in another clinical trial and receiving an investigational medicinal product within 90 days prior to the Screening Visit (Visit 1).
  16. Previous treatment with an ocular gene therapy product.
  17. Participants who have undergone ocular surgery of clinical relevance (per Investigator opinion) within 90 days preceding the Screening Visit (Visit 1).
  18. Female participants who are or who intend to breast feed during the trial period.

Exclusion Criteria:

Participants who meet at least one of the following criteria at the Inclusion Visit (Visit 2) will not be included in the study.

  1. Any non-selection criteria which may have appeared after the Screening visit.
  2. Participants taking idebenone who have not completely discontinued the idebenone at least 7 days prior to Visit 2. If the participant has not discontinued idebenone at least 7 days prior to Visit 2, the visit may be delayed until the 7-day period is complete.
  3. Presence, at the time of study inclusion, of infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
  4. Presence of systemic illness, including alcohol and drug abuse (except nicotine), or medically significant abnormal laboratory values that are deemed by the Investigator to preclude the participant's safe participation in the study.
  5. Presence of illness or disease that, in the opinion of the Investigator, include symptoms and/or the associated treatments that can alter visual function, for instance cancers or pathology of the central nervous system.
  6. Any medical or psychological condition that, in the opinion of the Investigator, may compromise the safe participation of the participant in the study or would preclude compliance with the study protocol or ability of the participant to successfully complete the study.
  7. Participants unable or unwilling to comply with the protocol requirements.

Trial design

Primary purpose




Interventional model

Parallel Assignment


Quadruple Blind

39 participants in 2 patient groups

GS010-treated Eyes
Experimental group
Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.
Biological: GS010
Sham-treated Eyes
Sham Comparator group
Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.
Device: Sham Intravitreal Injection

Trial documents

Trial contacts and locations



Data sourced from clinicaltrials.gov

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