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

NCT00749957 | Completed Phase 1 Results DMC

• 2 other identifiers: AGTC-RPE65-002R01FD003694
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Leber Congenital Amaurosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Ocular or Non-ocular Adverse Events

  2 years

Secondary Outcomes (2)

• Participants With Changes in Visual Fields

  2 years

• Participants With Changes in Best Corrected Visual Acuity

  2 years

Study Arms (2)

1

EXPERIMENTAL

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

Biological: rAAV2-CB-hRPE65

2

EXPERIMENTAL

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

Biological: rAAV2-CB-hRPE65

Interventions

rAAV2-CB-hRPE65 BIOLOGICAL

Recombinant adeno-associated virus vector expressing RPE65

1; 2

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beacon Therapeutics: lead
• Oregon Health and Science University: collaborator
• University of Massachusetts, Worcester: collaborator

Study Sites (2)

University of Massachusetts Medical School

Worcester, Massachusetts, 01605, United States

Location

Casey Eye Institue, Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (5)

• 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.

  PMID: 16226919 BACKGROUND

• 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.

  PMID: 16942444 BACKGROUND

• 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.

  PMID: 27102010 BACKGROUND

• 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.

  PMID: 38888288 DERIVED

• 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.

  PMID: 29869534 DERIVED

Related Links

• Applied Genetic Technologies Corporation home page

MeSH Terms

Conditions

Leber Congenital Amaurosis

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Applied Genetic Technologies Corporation

jchulay@agtc.com

386-462-2204

Study Officials

• J Timothy Stout, MD, PhD, MBA

  Casey Eye Institute, Oregon Health & Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2008
• First Posted: September 10, 2008
• Study Start: June 17, 2009
• Primary Completion: September 23, 2014
• Study Completion: September 22, 2017
• Last Updated: December 28, 2017
• Results First Posted: April 8, 2016

Record last verified: 2017-10

Locations

US (2)