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Leber Congenital AmaurosisPhase 1/2NCT01208389

Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2

A Phase 1/2 study testing voretigene neparvovec-rzyl in people with Leber Congenital Amaurosis, run by Spark Therapeutics, Inc. at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The study is a follow-on to a Phase 1 dose-escalation and safety study. Read more about this study

Who is it for?
Ages 8 years and older
Conditions the study is for
Leber Congenital Amaurosis
What is being tested?
voretigene neparvovec-rzyl
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Nov 2010to Oct 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 8 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Prior participation in Phase 1 study with unilateral, subretinal administration of AAV2-hRPE65v2.
  • Visual acuity equal to or greater than light perception.
  • Sufficient viable retinal cells in contralateral, previously uninjected eye, 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 shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 50 degrees of fixation.
  • Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).

Who cannot join

  • Unable or unwilling to meet requirements of the study.
  • Participation in any other study of an investigational drug within 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.
  • Pre-existing eye conditions, such as glaucoma, or complicating systemic diseases that would preclude the planned surgery or could 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).
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  • Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for four months following vector administration.
  • Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, 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

1 site in 1 country.

United States1 site

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Follow-On Study to Evaluate the Safety of Re-Administration of Adeno-Associated Viral Vector Containing the Gene for Human RPE65 [AAV2-hRPE65v2] to the Contralateral Eye in Subjects With Leber Congenital Amaurosis (LCA) Previously Enrolled in a Phase 1 Study

The study is a follow-on to a Phase 1 dose-escalation and safety study.

Read the detailed description

The study is a follow-on to a Phase 1 dose-escalation and safety study (closed to enrollment as of June 2009). Up to twelve adults and children with a molecular diagnosis of biallelic RPE65 mutations, who have participated in the earlier Phase 1 study, and who meet all study eligibility criteria, will receive AAV2-hRPE65v2 vector in the previously uninjected, contralateral eye to evaluate the safety of bilateral, sequential subretinal administration of AAV2-hRPE65v2.

Being tested
voretigene neparvovec-rzyl
Medical subject headings
Leber Congenital Amaurosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • voretigene neparvovec-rzylBiological

    Also called AAV2-hRPE65v2

    One time, subretinal administration of 1.5E11 vg AAV2-hRPE65v2 vector in 300 microliters to the contralateral, previously uninjected eye.

Study groups in NCT01208389
Study groupRoleWhat they receive
voretigene neparvovec-rzyl (AAV2-hRPE65v2)ExperimentalAdministration of study agent (AAV2-hRPE65v2) to the previously, uninjected contralateral eye:
Receives: Biological: voretigene neparvovec-rzyl

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events as a measure of safety and tolerability

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

Secondary outcomes (6)

  1. Visual acuity

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

  2. Visual field

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

  3. Pupillary light response

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

  4. Mobility testing

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

  5. Full-field light threshold sensitivity testing

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

  6. Contrast sensitivity

    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

    Measured: 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionOct 2027 (estimated)
  4. Study completionOct 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01208389
Sponsor's protocol ID
AAV2-hRPE65v2-102
Other IDs
10-007752
Status last verified
Dec 2024
First submitted
22 Sep 2010
Last updated
29 Apr 2025
Results posted
No
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 18441370

  • Maguire 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 19854499

  • Simonelli 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 19953081

  • Bennett 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 22323828

  • Fischer 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 38254722

  • Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Elci OU, Chung DC, Sun J, Wright JF, Cross DR, Aravand P, Cyckowski LL, Bennicelli JL, Mingozzi F, Auricchio A, Pierce EA, Ruggiero J, Leroy BP, Simonelli F, High KA, Maguire AM. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016 Aug 13;388(10045):661-72. doi: 10.1016/S0140-6736(16)30371-3. Epub 2016 Jun 30.

    PubMed 27375040

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing voretigene neparvovec-rzyl in people with Leber Congenital Amaurosis, run by Spark Therapeutics, Inc. at 1 site 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 4 inclusion and 9 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 29 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 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Adverse events as a measure of safety and tolerability (time frame: 15 years). 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 NCT01208389, which also lists 6 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 29 Apr 2025.

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