Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration (AMD)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Avalanche Biotechnologies, Inc.
Information provided by (Responsible Party):
Prof. P. Elizabeth Rakoczy, Lions Eye Institute, Perth, Western Australia
ClinicalTrials.gov Identifier:
NCT01494805
First received: December 14, 2011
Last updated: April 9, 2014
Last verified: September 2012
  Purpose

The study will involve approximately 40 subjects aged 55 or above who have exudative age-related macular degeneration (wet AMD). Patients will be randomized to receive one of two doses of rAAV.sFlt-1 or assigned to the control group.


Condition Intervention Phase
Macular Degeneration
Age-related Maculopathies
Age-related Maculopathy
Maculopathies,Age-related
Maculopathy,Age-related
Retinal Degeneration
Retinal Neovascularization
Eye Diseases
Biological: rAAV.sFlt-1
Other: Control (ranibizumab alone)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I/II Controlled Dose-escalating Trial to Establish the Baseline Safety and Efficacy of a Single Subretinal Injection of rAAV.sFlt-1 Into Eyes of Patients With Exudative Age-related Macular Degeneration (AMD)

Resource links provided by NLM:


Further study details as provided by Lions Eye Institute, Perth, Western Australia:

Primary Outcome Measures:
  • No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection [ Time Frame: Primary endpoint at 1 month ] [ Designated as safety issue: Yes ]
    1. Ocular examination:

      • Ocular inflammation
      • Intraocular pressure
      • Visual acuity
      • Retinal bleeding
    2. Abnormal laboratory data


Secondary Outcome Measures:
  • Maintenance or improvement of vision without the necessity of ranibizumab re-injections [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    1. Best-corrected visual acuity
    2. CNV lesion
    3. Foveal thickness


Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low Dose rAAV.sFlt-1 Biological: rAAV.sFlt-1
1 x 10^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
Experimental: High Dose rAAV.sFlt-1 Biological: rAAV.sFlt-1
1 x 10^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
Active Comparator: Control - ranibizumab only Other: Control (ranibizumab alone)
Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).

Detailed Description:

A new treatment for exudative age-related macular degeneration (wet AMD) is being investigated. The purpose of this Phase I/II clinical research study is to examine the baseline safety and efficacy of an experimental study drug to treat a complication of the disease which leads to vision loss. The name of the study drug is rAAV.sFlt-1.

This experimental study uses a non-pathogenic virus to express a therapeutic protein within the eye. The therapeutic diminishes the growth of abnormal blood vessels under the retina. The duration of effect is thought to be long-term (years) following a single administration.

The clinical research study will look at the baseline safety and efficacy of a single injection of rAAV.sFlt-1 injected directly into the eye.

Approximately forty (40) subjects will participate in Australia. The primary endpoint of the study is at one month, with extended follow up for 3 years.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 55 years;
  • Subfoveal CNV secondary to AMD and with best corrected visual acuity of 3/60 - 6/9 with 6/60 or better in the other eye;
  • Fluorescein angiogram of the study eye must show evidence of a leaking subfoveal choroidal neovascular lesion, or CNV currently under active management with anti-VEGF therapy;
  • Must be a candidate for anti-VEGF intravitreal injections;
  • No previous retinal treatment of photodynamic therapy or laser;
  • Able to provide informed consent;
  • Able to comply with protocol requirements, including follow-up visits.

Exclusion Criteria:

  • Liver enzymes > 2 X upper limit of normal;
  • Any prior treatment for AMD in the study / control eye, excluding anti-VEGF injections;
  • Extensive sub-foveal scarring, extensive geographic atrophy, or thick subretinal blood in the study eye as determined by the investigator;
  • Significant retinal disease other than sub-foveal CNV AMD;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01494805

Locations
Australia, Western Australia
Lions Eye Institute
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
Lions Eye Institute, Perth, Western Australia
Avalanche Biotechnologies, Inc.
Investigators
Principal Investigator: Ian Constable, Professor Lions Eye Institute
  More Information

No publications provided

Responsible Party: Prof. P. Elizabeth Rakoczy, Principal Scientific Investigator, Lions Eye Institute, Perth, Western Australia
ClinicalTrials.gov Identifier: NCT01494805     History of Changes
Other Study ID Numbers: 2008-135
Study First Received: December 14, 2011
Last Updated: April 9, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Lions Eye Institute, Perth, Western Australia:
Retinal Degeneration
Age-related Macular Degeneration
AAV
AMD
Wet AMD
Neovascular AMD
Gene Therapy
Ocular
Ocular Gene Therapy
Eye diseases
Macular Degeneration
Retinal Neovascularization
Wet Macular Degeneration
Retinal Diseases

Additional relevant MeSH terms:
Eye Diseases
Macular Degeneration
Neovascularization, Pathologic
Retinal Degeneration
Retinal Neovascularization
Wet Macular Degeneration
Retinal Diseases
Metaplasia
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014