Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis

NCT ID: NCT00749957

Last Updated: 2017-12-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-17

Study Completion Date

2017-09-22

Brief Summary

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The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the RPE65 gene.

Funding Source - FDA OOPD

Detailed Description

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This will be a non-randomized, open label study. A total of 12 participants will be enrolled into two groups of 6 each. Each participant will receive rAAV2 CB hRPE65 by subretinal injection in one eye on a single occasion. Participants in Group 1 will receive 450 µL at a dosage level of 4 x 10\^11 vg/mL containing a total of 1.8 x 10\^11 vg of rAAV2-CB-hRPE65. Participants in Group 2 will receive 450 µL at a dosage level of 1.33 x 10\^12 vg/mL containing a total of 6 x 10\^11 vg of rAAV2-CB-hRPE65. A retinal surgeon will administer the vector by subretinal injection.

Enrollment will begin with Group 1 and will proceed to Group 2 after review of safety data by a Data and Safety Monitoring Committee.

Safety will be monitored by evaluation of ocular and non ocular adverse events and hematology and clinical chemistry parameters. Efficacy will be measured by evaluation of visual fields, visual acuity and electroretinography.

Conditions

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Leber Congenital Amaurosis

Keywords

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AAV adeno-associated virus RPE65 Leber congenital amaurosis LCA gene therapy human gene transfer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Subjects at least 6 y/o treated with a lower dose of the vector by subretinal injection

Group Type EXPERIMENTAL

rAAV2-CB-hRPE65

Intervention Type BIOLOGICAL

Recombinant adeno-associated virus vector expressing RPE65

2

Subjects at least 6 y/o treated with a higher dose of the vector by subretinal injection

Group Type EXPERIMENTAL

rAAV2-CB-hRPE65

Intervention Type BIOLOGICAL

Recombinant adeno-associated virus vector expressing RPE65

Interventions

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rAAV2-CB-hRPE65

Recombinant adeno-associated virus vector expressing RPE65

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Retinal disease consistent with a diagnosis of Leber congenital amaurosis and documented mutations in the RPE65 gene (including null mutations and mutations that code for abnormal RPE65 protein);
* At least 6 years of age;
* Good general health without significant physical examination findings or clinically significant abnormal laboratory results;
* Able to perform tests of visual and retinal function;
* Visual acuity not better than 20/60 and not worse than hand motion in both the treated eye and the fellow eye;
* Visible photoreceptor (outer nuclear) layer on a standard optical coherence tomography (OCT) scan;
* Acceptable hematology, clinical chemistry and urine laboratory parameters;
* For females of childbearing potential, a negative pregnancy test at screening and at baseline, and agreement to use effective contraception for 12 months after administration of rAAV2-CB-hRPE65, for sexual activity that could lead to pregnancy;
* For males of reproductive potential, agreement to use effective contraception for 12 months after administration of rAAV2-CB-hRPE65, for sexual activity that could lead to pregnancy

Exclusion Criteria

* Pre-existing eye conditions that would preclude the planned surgery or interfere with interpretation of study endpoints or complications of surgery (e.g. glaucoma, corneal or lenticular opacities, or history or retinal detachment);
* Presence of epiretinal membrane on OCT;
* History of immunodeficiency or other medical conditions that might increase the risk of rAAV2-CB-hRPE65 administration;
* Use of anticoagulants or anti-platelet agents within 7 days prior to study agent administration;
* History of allergy or sensitivity to medications planned for use in the peri-operative period;
* For females of childbearing potential, a positive pregnancy test at screening or baseline (within 2 days before rAAV2-CB-hRPE65 administration);
* Females who are breast feeding;
* Use of any investigational agent, or systemic corticosteroids or other immunosuppressive drug(s), within 3 months prior to enrollment;
* Prior receipt of any AAV gene therapy product;
* Any condition which leads the investigator to believe that the participant cannot comply with the protocol requirements or that may place the participant at an unacceptable risk for participation.
Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oregon Health and Science University

OTHER

Sponsor Role collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role collaborator

Beacon Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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J Timothy Stout, MD, PhD, MBA

Role: PRINCIPAL_INVESTIGATOR

Casey Eye Institute, Oregon Health & Science University

Locations

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University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Casey Eye Institue, Oregon Health & Science University

Portland, Oregon, United States

Site Status

Countries

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United States

References

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Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. 2005 Dec;12(6):1072-82. doi: 10.1016/j.ymthe.2005.08.008. Epub 2005 Oct 14.

Reference Type BACKGROUND
PMID: 16226919 (View on PubMed)

Jacobson SG, Boye SL, Aleman TS, Conlon TJ, Zeiss CJ, Roman AJ, Cideciyan AV, Schwartz SB, Komaromy AM, Doobrajh M, Cheung AY, Sumaroka A, Pearce-Kelling SE, Aguirre GD, Kaushal S, Maguire AM, Flotte TR, Hauswirth WW. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum Gene Ther. 2006 Aug;17(8):845-58. doi: 10.1089/hum.2006.17.845.

Reference Type BACKGROUND
PMID: 16942444 (View on PubMed)

Weleber RG, Pennesi ME, Wilson DJ, Kaushal S, Erker LR, Jensen L, McBride MT, Flotte TR, Humphries M, Calcedo R, Hauswirth WW, Chulay JD, Stout JT. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Ophthalmology. 2016 Jul;123(7):1606-20. doi: 10.1016/j.ophtha.2016.03.003. Epub 2016 Apr 19.

Reference Type BACKGROUND
PMID: 27102010 (View on PubMed)

Ku CA, Igelman AD, Huang SJ, Bailey ST, Lauer AK, Duncan JL, Weleber RG, Yang P, Pennesi ME. Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector. Transl Vis Sci Technol. 2024 Jun 3;13(6):11. doi: 10.1167/tvst.13.6.11.

Reference Type DERIVED
PMID: 38888288 (View on PubMed)

Pennesi ME, Weleber RG, Yang P, Whitebirch C, Thean B, Flotte TR, Humphries M, Chegarnov E, Beasley KN, Stout JT, Chulay JD. Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy. Hum Gene Ther. 2018 Dec;29(12):1428-1437. doi: 10.1089/hum.2018.014. Epub 2018 Jul 24.

Reference Type DERIVED
PMID: 29869534 (View on PubMed)

Related Links

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http://agtc.com

Applied Genetic Technologies Corporation home page

Other Identifiers

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R01FD003694

Identifier Type: FDA

Identifier Source: secondary_id

View Link

AGTC-RPE65-002

Identifier Type: -

Identifier Source: org_study_id