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
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: 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 July 22, 2014