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

Primary Purpose

Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
rAAV.sFlt-1
rAAV.sFlt-1
Control (ranibizumab alone)
Sponsored by
Lions Eye Institute, Perth, Western Australia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Macular Degeneration focused on measuring Age-related Macular Degeneration, AAV, AMD, Wet AMD, Neovascular AMD, Gene Therapy, Ocular, Ocular Gene Therapy, Eye diseases, Macular Degeneration, Retinal Degeneration, Retinal Neovascularization, Wet Macular Degeneration, Retinal Diseases

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Lions Eye Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Low Dose rAAV.sFlt-1

High Dose rAAV.sFlt-1

Control - ranibizumab only

Arm Description

Outcomes

Primary Outcome Measures

No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection
Ocular examination: Ocular inflammation Intraocular pressure Visual acuity Retinal bleeding Abnormal laboratory data

Secondary Outcome Measures

Maintenance or improvement of vision without the necessity of ranibizumab re-injections
Best-corrected visual acuity CNV lesion Foveal thickness

Full Information

First Posted
December 14, 2011
Last Updated
August 30, 2017
Sponsor
Lions Eye Institute, Perth, Western Australia
Collaborators
Adverum Biotechnologies, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01494805
Brief Title
Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration
Acronym
AMD
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 2011 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lions Eye Institute, Perth, Western Australia
Collaborators
Adverum Biotechnologies, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy, Maculopathies,Age-related, Maculopathy,Age-related, Retinal Degeneration, Retinal Neovascularization, Eye Diseases
Keywords
Age-related Macular Degeneration, AAV, AMD, Wet AMD, Neovascular AMD, Gene Therapy, Ocular, Ocular Gene Therapy, Eye diseases, Macular Degeneration, Retinal Degeneration, Retinal Neovascularization, Wet Macular Degeneration, Retinal Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Dose rAAV.sFlt-1
Arm Type
Experimental
Arm Title
High Dose rAAV.sFlt-1
Arm Type
Experimental
Arm Title
Control - ranibizumab only
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
rAAV.sFlt-1
Intervention Description
1 x 10^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
Intervention Type
Biological
Intervention Name(s)
rAAV.sFlt-1
Intervention Description
1 x 10^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
Intervention Type
Other
Intervention Name(s)
Control (ranibizumab alone)
Intervention Description
Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).
Primary Outcome Measure Information:
Title
No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection
Description
Ocular examination: Ocular inflammation Intraocular pressure Visual acuity Retinal bleeding Abnormal laboratory data
Time Frame
Primary endpoint at 1 month
Secondary Outcome Measure Information:
Title
Maintenance or improvement of vision without the necessity of ranibizumab re-injections
Description
Best-corrected visual acuity CNV lesion Foveal thickness
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian Constable, Professor
Organizational Affiliation
Lions Eye Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lions Eye Institute
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
27865764
Citation
Constable IJ, Pierce CM, Lai CM, Magno AL, Degli-Esposti MA, French MA, McAllister IL, Butler S, Barone SB, Schwartz SD, Blumenkranz MS, Rakoczy EP. Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. EBioMedicine. 2016 Dec;14:168-175. doi: 10.1016/j.ebiom.2016.11.016. Epub 2016 Nov 10.
Results Reference
derived
PubMed Identifier
26431823
Citation
Rakoczy EP, Lai CM, Magno AL, Wikstrom ME, French MA, Pierce CM, Schwartz SD, Blumenkranz MS, Chalberg TW, Degli-Esposti MA, Constable IJ. Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Lancet. 2015 Dec 12;386(10011):2395-403. doi: 10.1016/S0140-6736(15)00345-1. Epub 2015 Sep 30.
Results Reference
derived

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

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