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

Leber Congenital Amaurosis Clinical Trial

Official title:

A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing RPE65 (rAAV2-CB-hRPE65) in Patients With Leber Congenital Amaurosis Type 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00749957
• Other study ID #: AGTC-RPE65-002
• Secondary ID: R01FD003694
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 8, 2008
• Last updated: December 1, 2017
• Start date: June 17, 2009
• Est. completion date: September 22, 2017

Study information

• Verified date: October 2017
• Source: Applied Genetic Technologies Corp
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 22, 2017
• Est. primary completion date: September 23, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blindness
• Leber Congenital Amaurosis

Intervention

Biological:
• rAAV2-CB-hRPE65
Recombinant adeno-associated virus vector expressing RPE65

Locations

Country	Name	City	State
United States	Casey Eye Institue, Oregon Health & Science University	Portland	Oregon
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Applied Genetic Technologies Corp	Oregon Health and Science University, University of Massachusetts, Worcester

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2005 Oct 14. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Ocular or Non-ocular Adverse Events		2 years
Secondary	Participants With Changes in Visual Fields	Improvement in the central 30 degree visual field, measured by static perimetry, at one or more time points after treatment, that was greater than the limit of agreement for baseline values .	2 years
Secondary	Participants With Changes in Best Corrected Visual Acuity	Increase in BCVA of 7 or more letters at Year 2 visit compared to average baseline value	2 years

External Links

•   Applied Genetic Technologies Corporation home page