Inherited Retinal Dystrophy Due to RPE65 MutationsPhase 3NCT00999609
Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
A Phase 3 study testing AAV2-hRPE65v2,voretigene neparvovec-rzyl in people with Inherited Retinal Dystrophy Due to RPE65 Mutations and Leber Congenital Amaurosis, run by Spark Therapeutics, Inc. at 2 sites in United States.
Trial summary
The study is a Phase 3, open-label, randomized controlled trial of gene therapy intervention by subretinal administration of AAV2-hRPE65v2 (voretigene neparvovec-rzyl). At least twenty-four subjects, three years of age or older, will be recruited. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Inherited Retinal Dystrophy Due to RPE65 Mutations, Leber Congenital Amaurosis
- What is being tested?
- AAV2-hRPE65v2,voretigene neparvovec-rzyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2012to Jan 2030
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).
- Diagnosis of LCA due to RPE65 mutations; molecular diagnosis is to be performed, or confirmed, by a CLIA-approved laboratory.
- Age three years old or older.
- Visual acuity worse than 20/60 (both eyes) and/or visual field less than 20 degrees in any meridian as measured by a III4e isopter or equivalent (both eyes).
- Sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of >100 µm thickness shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 30 degrees of fixation as measured by a III4e isopter or equivalent.
- Subjects must be evaluable on mobility testing (the primary efficacy endpoint) to be eligible for the study. Evaluable is defined as: 1) The ability to perform mobility testing within the luminance range evaluated in the study. Individuals must receive an accuracy score of ≤ 1 during screening mobility testing at 400 lux or less to be eligible; individuals with an accuracy score of > 1 on all screening mobility test runs at 400 lux, or those who refuse to perform mobility testing at screening, will be excluded. 2) The inability to pass mobility testing at 1 lux. Individuals must fail screening mobility testing at 1 lux to be eligible; individuals that pass one or more screening mobility test runs at 1 lux will be excluded.
Who cannot join
- Unable or unwilling to meet requirements of the study, including receiving bilateral subretinal vector administrations.
- Any prior participation in a study in which a gene therapy vector was administered.
- Participation in a clinical study with an investigational drug in the past six months.
- Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
- Prior intraocular surgery within six months.
- Known sensitivity to medications planned for use in the peri-operative period.
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- Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery or interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example: radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g., macular edema or proliferative changes). Also excluded would be subjects with immunodeficiency (acquired or congenital) as there could be susceptibility to opportunistic infection (such as CMV retinitis).
- Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for four months following vector administration.
- Individuals incapable of performing mobility testing (the primary efficacy endpoint) for reason other than poor vision, including physical or attentional limitations.
- Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study or, in the opinion of the investigator, makes the potential subject unsuitable for the study.
- Subjects will not be excluded based on their gender, race, or ethnicity.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Iowa
Iowa City, Iowa, 52242
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]
The study is a Phase 3, open-label, randomized controlled trial of gene therapy intervention by subretinal administration of AAV2-hRPE65v2 (voretigene neparvovec-rzyl). At least twenty-four subjects, three years of age or older, will be recruited. The intervention group will receive AAV2-hRPE65v2 at either The Children's Hospital of Philadelphia or University of Iowa to determine if it improves visual and retinal function in individuals with RPE65 gene mutations.
Read the detailed description
Leber congenital amaurosis (LCA) is a disease where part of the eye (the retina) is severely diseased. Usually it is detected in affected people within the first few months of life, as there is significantly poor vision at birth. Cells in the retina are lost over time in people with LCA, which typically leads to total blindness. There are no pharmacological treatments available. This study will focus on the form of LCA caused by changes (mutations) in DNA that makes a certain protein (called the 65 kDa retinal pigment epithelium (RPE)-specific protein, or RPE65). This can be confirmed by a special method of testing (molecular testing) to verify the presence of RPE65 gene mutations.
This study uses a gene therapy vector made from an adeno-associated virus (AAV) called AAV2-hRPE65v2 (voretigene neparovec-rzyl). Gene therapy refers to the incorporation of new DNA into cells with the goal of supplying a therapeutic gene or a gene that is missing or not functioning in the cell. The AAV parts of the gene therapy vector work as a delivery vehicle for providing the normal human RPE65 gene to the cells of the retina. An earlier Phase 1 clinical study of AAV2-hRPE65v2 was conducted based on the demonstration of safety and effectiveness of the vector in animals with a similar eye disease. The earlier Phase 1 clinical study was a dose-escalation study primarily designed to evaluate safety in humans, and tested three doses of the vector in twelve children and adults. The safety of injecting into the second eye was also evaluated. The results from these earlier Phase 1 studies showed an acceptable safety profile.
This study will deliver AAV2-hRPE65v2 vector (voretigene neparvovec-rzyl) to at least sixteen intervention group subjects, age three or older; subjects will receive the vector in both eyes via subretinal injections during surgeries (on separate days). The purpose of this research study is to assess the efficacy and safety of the AAV2-hRPE65v2 gene therapy vector (voretigene neparvovec-rzyl) as a possible treatment for LCA due to RPE65 gene mutations. The control group of at least eight subjects will be able to cross-over to the intervention group after one year, provided they still meet all eligibility criteria.
- Being tested
- AAV2-hRPE65v2,voretigene neparvovec-rzyl
- Keywords
- Adeno-associated virus, AAV, Leber congenital amaurosis, RPE65, Gene therapy, Gene transfer, voretigene neparvovec-rzyl, Retinitis pigmentosa
- Medical subject headings
- Leber Congenital Amaurosis, Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV2-hRPE65v2,voretigene neparvovec-rzylBiological
Also called AAV2-hRPE65v2, voretigene neparvovec-rzyl, gene therapy vector
Subretinal administration of gene therapy vector AAV2-hRPE65v2 (1.5E11 vector genomes per eye) to both eyes via surgical procedures on separate days.
| Study group | Role | What they receive |
|---|---|---|
| AAV2-hRPE65v2,voretigene neparvovec-rzyl | Experimental | voretigene neparvovec rzyl, 1.5 E11 vector genomes, per eye, administered by subretinal injection in a volume of 0.3mL, 6-18 days apart Receives: Biological: AAV2-hRPE65v2,voretigene neparvovec-rzyl |
| Control | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multi-luminance Mobility Testing (MLMT), Bilateral
The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
Measured: One year (change from baseline)
Secondary outcomes (3)
Full-field Light Sensitivity Threshold (FST) Testing: White Light
Measures the light sensitivity of the entire visual field by recording the luminance at which a subject reliably reports seeing the dimmest flash.
Measured: One year (change from baseline)
Multi-luminance Mobility Testing (Monocular)
The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using the first eye at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
Measured: One year (change from baseline)
Visual Acuity
Measurement of the sharpness of vision, determined by the ability to read letters on a standardized chart from a specified distance.
Measured: One year (change from baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2009 (estimated)
- Study startOct 2012
- Primary completionJul 2015
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Inherited Retinal Dystrophy Due to RPE65 MutationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spark Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Children's Hospital of Philadelphia, University of Iowa
- Responsible party
- Sponsor
- Investigators
- Albert M Maguire, MD, Principal investigator, Children's Hospital of PhiladelphiaStephen R Russell, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00999609
- Sponsor's protocol ID
- AAV2-hRPE65v2-301
- Status last verified
- Apr 2025
- First submitted
- 21 Oct 2009
- Last updated
- 23 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27.
PubMed 18441370Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, Mingozzi F, Bennicelli JL, Ying GS, Rossi S, Fulton A, Marshall KA, Banfi S, Chung DC, Morgan JI, Hauck B, Zelenaia O, Zhu X, Raffini L, Coppieters F, De Baere E, Shindler KS, Volpe NJ, Surace EM, Acerra C, Lyubarsky A, Redmond TM, Stone E, Sun J, McDonnell JW, Leroy BP, Simonelli F, Bennett J. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009 Nov 7;374(9701):1597-605. doi: 10.1016/S0140-6736(09)61836-5. Epub 2009 Oct 23.
PubMed 19854499Chung DC, McCague S, Yu ZF, Thill S, DiStefano-Pappas J, Bennett J, Cross D, Marshall K, Wellman J, High KA. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies. Clin Exp Ophthalmol. 2018 Apr;46(3):247-259. doi: 10.1111/ceo.13022. Epub 2017 Aug 31.
PubMed 28697537Chung DC, Bertelsen M, Lorenz B, Pennesi ME, Leroy BP, Hamel CP, Pierce E, Sallum J, Larsen M, Stieger K, Preising M, Weleber R, Yang P, Place E, Liu E, Schaefer G, DiStefano-Pappas J, Elci OU, McCague S, Wellman JA, High KA, Reape KZ. The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene. Am J Ophthalmol. 2019 Mar;199:58-70. doi: 10.1016/j.ajo.2018.09.024. Epub 2018 Sep 28.
PubMed 30268864Ashtari M, Cyckowski LL, Monroe JF, Marshall KA, Chung DC, Auricchio A, Simonelli F, Leroy BP, Maguire AM, Shindler KS, Bennett J. The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest. 2011 Jun;121(6):2160-8. doi: 10.1172/JCI57377. Epub 2011 May 23.
PubMed 21606598Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther. 2010 Mar;18(3):643-50. doi: 10.1038/mt.2009.277. Epub 2009 Dec 1.
PubMed 19953081Bennett J, Ashtari M, Wellman J, Marshall KA, Cyckowski LL, Chung DC, McCague S, Pierce EA, Chen Y, Bennicelli JL, Zhu X, Ying GS, Sun J, Wright JF, Auricchio A, Simonelli F, Shindler KS, Mingozzi F, High KA, Maguire AM. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012 Feb 8;4(120):120ra15. doi: 10.1126/scitranslmed.3002865.
PubMed 22323828Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14.
PubMed 28712537Fischer MD, Simonelli F, Sahni J, Holz FG, Maier R, Fasser C, Suhner A, Stiehl DP, Chen B, Audo I, Leroy BP; PERCEIVE Study Group. Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study. Biomolecules. 2024 Jan 17;14(1):122. doi: 10.3390/biom14010122.
PubMed 38254722Bhadhuri A, Droschel D, Guldimann M, Jetschgo C, Banhazi J, Schwenkglenks M, Sutherland CS. Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland. BMC Health Serv Res. 2022 Jun 28;22(1):837. doi: 10.1186/s12913-022-08211-y.
PubMed 35765055
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]
- ClinicalTrials.gov ID
- NCT00999609
- Acronym / sponsor ID
- AAV2-hRPE65v2-301
- Keywords
- Adeno-associated virus, AAV, Leber congenital amaurosis, RPE65, Gene therapy, Gene transfer, voretigene neparvovec-rzyl, Retinitis pigmentosa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Spark Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Children's Hospital of Philadelphia, University of Iowa
- Study start
- Oct 2012 (actual)
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jan 2030 (estimated)
- First posted
- 22 Oct 2009 (estimated)
- Results
- Posted 26 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a Phase 3, open-label, randomized controlled trial of gene therapy intervention by subretinal administration of AAV2-hRPE65v2 (voretigene neparvovec-rzyl). At least twenty-four subjects, three years of age or older, will be recruited. The intervention group will receive AAV2-hRPE65v2 at either The Children's Hospital of Philadelphia or University of Iowa to determine if it improves visual and retinal function in individuals with RPE65 gene mutations.
Detailed description
Leber congenital amaurosis (LCA) is a disease where part of the eye (the retina) is severely diseased. Usually it is detected in affected people within the first few months of life, as there is significantly poor vision at birth. Cells in the retina are lost over time in people with LCA, which typically leads to total blindness. There are no pharmacological treatments available. This study will focus on the form of LCA caused by changes (mutations) in DNA that makes a certain protein (called the 65 kDa retinal pigment epithelium (RPE)-specific protein, or RPE65). This can be confirmed by a special method of testing (molecular testing) to verify the presence of RPE65 gene mutations.
This study uses a gene therapy vector made from an adeno-associated virus (AAV) called AAV2-hRPE65v2 (voretigene neparovec-rzyl). Gene therapy refers to the incorporation of new DNA into cells with the goal of supplying a therapeutic gene or a gene that is missing or not functioning in the cell. The AAV parts of the gene therapy vector work as a delivery vehicle for providing the normal human RPE65 gene to the cells of the retina. An earlier Phase 1 clinical study of AAV2-hRPE65v2 was conducted based on the demonstration of safety and effectiveness of the vector in animals with a similar eye disease. The earlier Phase 1 clinical study was a dose-escalation study primarily designed to evaluate safety in humans, and tested three doses of the vector in twelve children and adults. The safety of injecting into the second eye was also evaluated. The results from these earlier Phase 1 studies showed an acceptable safety profile.
This study will deliver AAV2-hRPE65v2 vector (voretigene neparvovec-rzyl) to at least sixteen intervention group subjects, age three or older; subjects will receive the vector in both eyes via subretinal injections during surgeries (on separate days). The purpose of this research study is to assess the efficacy and safety of the AAV2-hRPE65v2 gene therapy vector (voretigene neparvovec-rzyl) as a possible treatment for LCA due to RPE65 gene mutations. The control group of at least eight subjects will be able to cross-over to the intervention group after one year, provided they still meet all eligibility criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AAV2-hRPE65v2,voretigene neparvovec-rzyl | Experimental | Biological: AAV2-hRPE65v2,voretigene neparvovec-rzylvoretigene neparvovec rzyl, 1.5 E11 vector genomes, per eye, administered by subretinal injection in a volume of 0.3mL, 6-18 days apart |
| Control | No intervention | –No intervention |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).
- Diagnosis of LCA due to RPE65 mutations; molecular diagnosis is to be performed, or confirmed, by a CLIA-approved laboratory.
- Age three years old or older.
- Visual acuity worse than 20/60 (both eyes) and/or visual field less than 20 degrees in any meridian as measured by a III4e isopter or equivalent (both eyes).
- Sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of >100 µm thickness shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 30 degrees of fixation as measured by a III4e isopter or equivalent.
Key exclusion criteria (11 listed)
- Unable or unwilling to meet requirements of the study, including receiving bilateral subretinal vector administrations.
- Any prior participation in a study in which a gene therapy vector was administered.
- Participation in a clinical study with an investigational drug in the past six months.
- Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
- Prior intraocular surgery within six months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV2-hRPE65v2,voretigene neparvovec-rzylAlso: AAV2-hRPE65v2, voretigene neparvovec-rzyl, gene therapy vectorSubretinal administration of gene therapy vector AAV2-hRPE65v2 (1.5E11 vector genomes per eye) to both eyes via surgical procedures on separate days. | Biological | AAV2-hRPE65v2,voretigene neparvovec-rzyl |
Primary outcome
Multi-luminance Mobility Testing (MLMT), Bilateral
Time frame: One year (change from baseline)
The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
3 secondary outcomes
Full-field Light Sensitivity Threshold (FST) Testing: White Light
Time frame: One year (change from baseline)
Multi-luminance Mobility Testing (Monocular)
Time frame: One year (change from baseline)
Visual Acuity
Time frame: One year (change from baseline)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18441370Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27.
- Background: PubMed 19854499Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, Mingozzi F, Bennicelli JL, Ying GS, Rossi S, Fulton A, Marshall KA, Banfi S, Chung DC, Morgan JI, Hauck B, Zelenaia O, Zhu X, Raffini L, Coppieters F, De Baere E, Shindler KS, Volpe NJ, Surace EM, Acerra C, Lyubarsky A, Redmond TM, Stone E, Sun J, McDonnell JW, Leroy BP, Simonelli F, Bennett J. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009 Nov 7;374(9701):1597-605. doi: 10.1016/S0140-6736(09)61836-5. Epub 2009 Oct 23.
- Background: PubMed 28697537Chung DC, McCague S, Yu ZF, Thill S, DiStefano-Pappas J, Bennett J, Cross D, Marshall K, Wellman J, High KA. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies. Clin Exp Ophthalmol. 2018 Apr;46(3):247-259. doi: 10.1111/ceo.13022. Epub 2017 Aug 31.
- Background: PubMed 30268864Chung DC, Bertelsen M, Lorenz B, Pennesi ME, Leroy BP, Hamel CP, Pierce E, Sallum J, Larsen M, Stieger K, Preising M, Weleber R, Yang P, Place E, Liu E, Schaefer G, DiStefano-Pappas J, Elci OU, McCague S, Wellman JA, High KA, Reape KZ. The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene. Am J Ophthalmol. 2019 Mar;199:58-70. doi: 10.1016/j.ajo.2018.09.024. Epub 2018 Sep 28.
- Results publication: PubMed 21606598Ashtari M, Cyckowski LL, Monroe JF, Marshall KA, Chung DC, Auricchio A, Simonelli F, Leroy BP, Maguire AM, Shindler KS, Bennett J. The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest. 2011 Jun;121(6):2160-8. doi: 10.1172/JCI57377. Epub 2011 May 23.
- Results publication: PubMed 19953081Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther. 2010 Mar;18(3):643-50. doi: 10.1038/mt.2009.277. Epub 2009 Dec 1.
- Results publication: PubMed 22323828Bennett J, Ashtari M, Wellman J, Marshall KA, Cyckowski LL, Chung DC, McCague S, Pierce EA, Chen Y, Bennicelli JL, Zhu X, Ying GS, Sun J, Wright JF, Auricchio A, Simonelli F, Shindler KS, Mingozzi F, High KA, Maguire AM. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012 Feb 8;4(120):120ra15. doi: 10.1126/scitranslmed.3002865.
- Results publication: PubMed 28712537Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14.
- Derived from this study: PubMed 38254722Fischer MD, Simonelli F, Sahni J, Holz FG, Maier R, Fasser C, Suhner A, Stiehl DP, Chen B, Audo I, Leroy BP; PERCEIVE Study Group. Real-World Safety and Effectiveness of Voretigene Neparvovec: Results up to 2 Years from the Prospective, Registry-Based PERCEIVE Study. Biomolecules. 2024 Jan 17;14(1):122. doi: 10.3390/biom14010122.
- Derived from this study: PubMed 35765055Bhadhuri A, Droschel D, Guldimann M, Jetschgo C, Banhazi J, Schwenkglenks M, Sutherland CS. Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland. BMC Health Serv Res. 2022 Jun 28;22(1):837. doi: 10.1186/s12913-022-08211-y.
Related trials for Inherited Retinal Dystrophy Due to RPE65 Mutations
Active, not recruitingObservational study
Long-term Follow-up Study in Subjects Who Received Voretigene Neparvovec-rzyl (AAV2-hRPE65v2)
Inherited Retinal Dystrophy Due to RPE65 Mutations
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert M Maguire, MD principal investigator
Children's Hospital of Philadelphia
Stephen R Russell, MD principal investigator
University of Iowa
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AAV2-hRPE65v2,voretigene neparvovec-rzyl in people with Inherited Retinal Dystrophy Due to RPE65 Mutations and Leber Congenital Amaurosis, run by Spark Therapeutics, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Multi-luminance Mobility Testing (MLMT), Bilateral (time frame: One year (change from baseline)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00999609, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.