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Trial record 2 of 7 for:    GenSight | LHON

Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year (REFLECT)

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ClinicalTrials.gov Identifier: NCT03293524
Recruitment Status : Active, not recruiting
First Posted : September 26, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
GenSight Biologics

Brief Summary:
The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional & structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year.

Condition or disease Intervention/treatment Phase
Leber Hereditary Optic Neuropathy Genetic: GS010 Drug: Placebo Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Treatment Arm 1
Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 1 will receive intravitreal GS010 in both eyes.
Genetic: GS010
GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.

Placebo Comparator: Treatment Arm 2
Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 2 will receive GS010 in one eye and placebo intravitreal injection in the other eye.
Genetic: GS010
GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.

Drug: Placebo
The placebo is a BSS, sterile, apyrogenic solution and used for ocular surgery. The placebo will be administered via intravitreal injection in a volume of 90 μL.




Primary Outcome Measures :
  1. Best-Corrected Visual Acuity (BCVA) reported using Log of the Minimal Angle of Resolution (LogMAR) - 1 year [ Time Frame: at 1-Year post baseline treatment ]
    The primary endpoint will be the BCVA reported with LogMAR at 1-Year post-treatment in second affected/not yet affected eyes. The change from baseline in second affected/not yet affected eyes receiving GS010 and placebo will be the primary response of interest. LogMAR BCVA will be used for statistical purposes.


Secondary Outcome Measures :
  1. Best-Corrected Visual Acuity (BCVA) reported with LogMAR - 2 years [ Time Frame: at 2-Years post baseline treatment ]
    LogMAR BCVA at each timepoint of the follow-up period and at 2-years post-treatment, for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. The change from baseline of the LogMAR BCVA will be used for statistical analyses.

  2. Responder Analysis [ Time Frame: at 1-Year and 2-Years post baseline treatment ]

    Response status over time and at 1 and 2-years post baseline treatment. Response status will be assessed for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. Definitions of responder eyes include:

    1. Eyes whose LogMAR BCVA improves (i.e. decreases) by ≥ 0.3 LogMAR (equivalent to a gain of ≥ 15 ETDRS letters) compared to baseline.
    2. Eyes whose LogMAR BCVA does not increase (i.e. worsen) by ≥ 0.3 LogMAR (equivalent to eye that lose ≤ 15 ETDRS letters) compared to baseline.
    3. Eyes whose LogMAR visual acuity is < 1.0 (i.e. better than LogMAR 1.0, equivalent to better than Snellen acuity of 20/200).

  3. Spectral-Domain - Optical Coherence Tomography (SD-OCT) parameter [ Time Frame: at 1-Year and 2-Years post baseline treatment ]
    Parameters measured with SD-OCT over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well

  4. Humphrey Visual Field (HVF) parameter [ Time Frame: at 1-Year and 2-Years post baseline treatment ]
    Parameters measured with HVF 30-2 over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well

  5. Pelli Robson Low Vision Contrast Sensitivity parameter [ Time Frame: at 1-Year and 2-Years post baseline treatment ]
    Parameters measured with Pelli Robson Low Vision Contrast Sensitivity over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well

  6. Quality of Life: Visual Functioning Questionnaire-25 [ Time Frame: at 1-Year and 2-Years post baseline treatment ]
    Visual Functioning Questionnaire-25 at 1 and 2-years post-treatment

  7. Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire [ Time Frame: at 1-Year and 2-Years post baseline treatment ]
    36-Item Short Form Health Survey, version 2 Questionnaire at 1 and 2-years post-treatment.


Other Outcome Measures:
  1. Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: up to 2-Years post baseline treatment ]
    Adverse events (AEs) and serious adverse events (SAEs), including those that are treatment-emergent and non-treatment-emergent, throughout the study period and at each study visit. Incidence and severity of systemic and local (ocular) AEs and SAEs will be determined at each clinical site and for the entire study cohort.

  2. Physical examinations [ Time Frame: At 2-Years post baseline treatment ]
    Results of physical examinations

  3. Electrocardiograms [ Time Frame: At 2-Years post baseline treatment ]
    Results of Electrocardiograms (ECGs)

  4. Laboratory results [ Time Frame: At 2-Years post baseline treatment ]
    Results of laboratory tests from blood collection

  5. Immune response evaluations [ Time Frame: Up to 2-Years post baseline treatment ]

    Results of immune response evaluations

    1. Time course of the humoral immune response measured with Neutralizing Antibodies (Nab) against Adeno-associated virus vector 2 (AAV2)
    2. Time course of the cellular immune response against AAV2

  6. Blood Bio-dissemination of AAV2 Vector DNA [ Time Frame: up to 4 weeks post-treatment ]
    Results of bio-dissemination testing up to 4-weeks post-treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Selection Criteria:

  • Age 15 years or older on the date of signed informed consent.
  • Clinically manifested vision loss due to ND4 LHON, to any extent, in at least one eye.
  • Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).

Main Non-Selection Criteria:

  • Contraindication to intravitreal injection in any eye.
  • Subjects refusing to discontinue idebenone.
  • Previous vitrectomy in either eye.
  • Narrow angle in any eye contra-indicating pupillary dilation.
  • Presence of known/documented mutations, other than the G11778A ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system.
  • History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation.

Main Inclusion Criteria:

  • Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).
  • Each eye of the subject must maintain at least Hand Motion (HM) visual acuity, as defined by the study's SOP for visual acuity testing.
  • Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the subject's mitochondrial DNA.

Main Exclusion Criteria:

  • Light Perception (LP) or No Light Perception (NLP) visual acuity in any eye, as defined by the study's standard operating procedure (SOP) for visual acuity testing.
  • Presence of active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
  • Presence of alcoholism, alcohol dependence, or alcohol or drug abuse (excluding nicotine).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03293524


Locations
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United States, California
Doheny Eye Center UCLA Pasadena
Pasadena, California, United States, 91105
United States, Colorado
University of Colorado Health Eye Center
Aurora, Colorado, United States, 80045
United States, Georgia
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Pennsylvania
Wills Eye Institute - Ocular Oncology Service
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Vanderbilt Eye Institute
Nashville, Tennessee, United States, 37232
Belgium
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
France
CHNO Les Quinze Vingts
Paris, France, 75012
Italy
IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica
Bologna, Italy, 40139
Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
United Kingdom
Moorfields Eye Hospital
London, Greater London, United Kingdom, EC1V 2PD
Sponsors and Collaborators
GenSight Biologics

Additional Information:
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Responsible Party: GenSight Biologics
ClinicalTrials.gov Identifier: NCT03293524     History of Changes
Other Study ID Numbers: GS-LHON-CLIN-05
2017-002187-40 ( EudraCT Number )
First Posted: September 26, 2017    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GenSight Biologics:
Leber Hereditary Optic Atrophy
Leber Hereditary Optic Neuropathy
LHON
Heredity Optic Atrophy
Eye Diseases
Hereditary Eye Diseases
Inherited retinal dystrophies or degeneration
Inborn Genetic Disease
Gene Therapy
Intravitreal Injections
Mitochondrial Disease
AAV2 Vectors
Nervous System Diseases
Neurodegenerative Disease
Heredodegenerative Disorders of the Nervous System
Atrophy
Pathological Conditions, Anatomical
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Additional relevant MeSH terms:
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Optic Nerve Diseases
Optic Neuritis
Optic Atrophy, Hereditary, Leber
Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Optic Atrophies, Hereditary
Optic Atrophy
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases