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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Oregon Health and Science University
University of Massachusetts, Worcester
Information provided by (Responsible Party):
Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier:
NCT00749957
First received: September 8, 2008
Last updated: March 6, 2013
Last verified: March 2013

September 8, 2008
March 6, 2013
December 2008
September 2014   (final data collection date for primary outcome measure)
Number and proportion of participants experiencing ocular or non-ocular adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Number and proportion of participants experiencing ocular or non-ocular adverse events [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00749957 on ClinicalTrials.gov Archive Site
  • Changes in visual fields [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Changes in best corrected visual acuity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Changes in visual fields [ Designated as safety issue: Yes ]
  • Changes in best corrected visual acuity [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
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

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

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leber Congenital Amaurosis
Biological: rAAV2-CB-hRPE65
Recombinant adeno-associated virus vector expressing RPE65
  • Experimental: 1
    Subjects at least 6 y/o treated with a lower dose of the vector by subretinal injection
    Intervention: Biological: rAAV2-CB-hRPE65
  • Experimental: 2
    Subjects at least 6 y/o treated with a higher dose of the vector by subretinal injection
    Intervention: Biological: rAAV2-CB-hRPE65

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
December 2027
September 2014   (final data collection date for primary outcome measure)

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.
Both
6 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00749957
AGTC-RPE65-002, R01 FD003694
Yes
Applied Genetic Technologies Corp
Applied Genetic Technologies Corp
  • Oregon Health and Science University
  • University of Massachusetts, Worcester
Principal Investigator: J Timothy Stout, MD, PhD, MBA Casey Eye Institute, Oregon Health & Science University
Applied Genetic Technologies Corp
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP