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

NCT01208389 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AAV2-hRPE65v2-10210-007752
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Leber Congenital Amaurosis

Outcome Measures

Primary Outcomes (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.

  15 years

Secondary Outcomes (6)

• Visual acuity

  15 years

• Visual field

  15 years

• Pupillary light response

  15 years

• Mobility testing

  15 years

• Full-field light threshold sensitivity testing

  15 years

Study Arms (1)

voretigene neparvovec-rzyl (AAV2-hRPE65v2)

EXPERIMENTAL

Administration of study agent (AAV2-hRPE65v2) to the previously, uninjected contralateral eye:

Biological: voretigene neparvovec-rzyl

Interventions

voretigene neparvovec-rzyl BIOLOGICAL

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

Also known as: AAV2-hRPE65v2

voretigene neparvovec-rzyl (AAV2-hRPE65v2)

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Spark Therapeutics, Inc.: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (6)

• 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.

  PMID: 18441370 BACKGROUND

• 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.

  PMID: 19854499 BACKGROUND

• 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.

  PMID: 19953081 BACKGROUND

• 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.

  PMID: 22323828 BACKGROUND

• 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.

  PMID: 38254722 DERIVED

• 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.

  PMID: 27375040 DERIVED

MeSH Terms

Conditions

Leber Congenital Amaurosis

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Officials

• Clinical Director

  Spark Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 24, 2010
• Study Start: November 1, 2010
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 29, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)