Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Spark Therapeutics, LLC
ClinicalTrials.gov Identifier:
NCT01208389
First received: September 22, 2010
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

The study is a follow-on to a Phase 1 dose-escalation and safety study.


Condition Intervention Phase
Leber Congenital Amaurosis
Biological: AAV2-hRPE65v2
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Follow-On Study to Evaluate the Safety of Re-Administration of Adeno-Associated Viral Vector Containing the Gene for Human RPE65 [AAV2-hRPE65v2] to the Contralateral Eye in Subjects With Leber Congenital Amaurosis (LCA) Previously Enrolled in a Phase 1 Study

Resource links provided by NLM:


Further study details as provided by Spark Therapeutics, LLC:

Primary Outcome Measures:
  • Adverse events as a measure of safety and tolerability [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.


Secondary Outcome Measures:
  • Visual acuity [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

  • Visual field [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

  • Pupillary light response [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

  • Mobility testing [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

  • Full-field light threshold sensitivity testing [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.

  • Contrast sensitivity [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.


Estimated Enrollment: 12
Study Start Date: November 2010
Estimated Study Completion Date: November 2026
Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vector (AAV2-hRPE65v2)
Administration of study agent (AAV2-hRPE65v2) to the previously, uninjected contralateral eye:
Biological: AAV2-hRPE65v2
One time, subretinal administration of 1.5E11 vg AAV2-hRPE65v2 vector to the contralateral, previously uninjected eye.

Detailed Description:

The study is a follow-on to a Phase 1 dose-escalation and safety study (closed to enrollment as of June 2009). Up to twelve adults and children with molecular diagnosis of LCA2, who have participated in the earlier Phase 1 study, and who meet all study eligibility criteria, will receive AAV2-hRPE65v2 vector in the previously uninjected, contralateral eye to evaluate the safety of bilateral, sequential subretinal administration of AAV2-hRPE65v2.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior participation in Phase 1 study with unilateral, subretinal administration of AAV2-hRPE65v2.
  • Visual acuity equal to or greater than light perception.
  • Sufficient viable retinal cells in contralateral, previously uninjected eye, as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of > 100 µm shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 50 degrees of fixation.
  • Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).

Exclusion Criteria:

  • Unable or unwilling to meet requirements of the study.
  • Participation in any other study of an investigational drug within the past six months.
  • Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
  • Prior intraocular surgery within six months.
  • Known sensitivity to medications planned for use in the peri-operative period.
  • Pre-existing eye conditions, such as glaucoma, or complicating systemic diseases that would preclude the planned surgery or could interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example: radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Also excluded would be subjects with immunodeficiency (acquired or congenital) as there could be susceptibility to opportunistic infection (such as CMV retinitis).
  • Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for four months following vector administration.
  • Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.
  • Subjects will NOT be excluded based on their gender, race, or ethnicity.
  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: NCT01208389

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Spark Therapeutics, LLC
Investigators
Principal Investigator: Albert M Maguire, MD Children's Hospital of Philadelphia
  More Information

Publications:

Responsible Party: Spark Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT01208389     History of Changes
Other Study ID Numbers: AAV2-hRPE65v2-102, 10-007752
Study First Received: September 22, 2010
Last Updated: January 13, 2014
Health Authority: United States: Food and Drug Administration

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 August 28, 2014