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
  Purpose

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


Condition Intervention Phase
Leber Congenital Amaurosis
Biological: rAAV2-CB-hRPE65
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Applied Genetic Technologies Corp:

Primary Outcome Measures:
  • Number and proportion of participants experiencing ocular or non-ocular adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 12
Study Start Date: December 2008
Estimated Study Completion Date: December 2027
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Subjects at least 6 y/o treated with a lower dose of the vector by subretinal injection
Biological: rAAV2-CB-hRPE65
Recombinant adeno-associated virus vector expressing RPE65
Experimental: 2
Subjects at least 6 y/o treated with a higher dose of the vector by subretinal injection
Biological: rAAV2-CB-hRPE65
Recombinant adeno-associated virus vector expressing RPE65

Detailed 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.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749957

Locations
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01605
United States, Oregon
Casey Eye Institue, Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Applied Genetic Technologies Corp
Oregon Health and Science University
University of Massachusetts, Worcester
Investigators
Principal Investigator: J Timothy Stout, MD, PhD, MBA Casey Eye Institute, Oregon Health & Science University
  More Information

Additional Information:
Publications:
Responsible Party: Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier: NCT00749957     History of Changes
Other Study ID Numbers: AGTC-RPE65-002, R01 FD003694
Study First Received: September 8, 2008
Last Updated: March 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Applied Genetic Technologies Corp:
AAV
adeno-associated virus
RPE65
Leber congenital amaurosis
LCA
gene therapy
human gene transfer

Additional relevant MeSH terms:
Leber Congenital Amaurosis
Blindness
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on July 20, 2014