Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD) - Full Text View

Sponsor:	Genzyme
Information provided by (Responsible Party):	Genzyme
ClinicalTrials.gov Identifier:	NCT01024998

Purpose

This Phase 1 clinical research study will examine the safety and tolerability of an experimental gene transfer agent, AAV2-sFLT01, in patients with Neovascular Age-Related Macular Degeneration (AMD).

Condition	Intervention	Phase
Macular Degeneration Age-Related Maculopathies Age-Related Maculopathy Maculopathies, Age-Related Maculopathy, Age-Related Retinal Degeneration Retinal Neovascularization Gene Therapy Therapy, Gene Eye Diseases	Biological: AAV2-sFLT01	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1, Open-Label, Multi-Center, Dose-Escalating, Safety and Tolerability Study of a Single Intravitreal Injection of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis Help Me Understand Genetics

MedlinePlus related topics: Eye Diseases Macular Degeneration

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Maximum tolerated dose of a single uniocular intravitreal injection of AAV2-sFLT01 [ Time Frame: Time of treatment through Week 52 (referred to as the "core" study) ] [ Designated as safety issue: Yes ]
Number of Treatment Emergent Adverse Events [ Time Frame: Time of treatment through Week 52 (referred to as the "core" study) ] [ Designated as safety issue: Yes ]
Number of Treatment Emergent Adverse Events [ Time Frame: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Decreased retinal thickness [ Time Frame: Time of treatment through Week 52 (referred to as the "core" study) ] [ Designated as safety issue: No ]
Decreased retinal thickness [ Time Frame: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period) ] [ Designated as safety issue: No ]

Estimated Enrollment:	34
Study Start Date:	December 2009
Estimated Study Completion Date:	March 2017
Estimated Primary Completion Date:	March 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 2 x 10^8 vector genomes (vg) AAV2-sFLT01	Biological: AAV2-sFLT01 2 x 10^8 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
Experimental: 2 x 10^9 vector genomes (vg) AAV2-sFLT01	Biological: AAV2-sFLT01 2 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
Experimental: 6 x 10^9 vector genomes (vg) AAV2-sFLT01	Biological: AAV2-sFLT01 6 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
Experimental: 2 x 10^10 vector genomes (vg) AAV2-sFLT01	Biological: AAV2-sFLT01 2 x 10^10 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.

Detailed Description:

A new treatment for neovascular age-related macular degeneration (AMD) is being investigated. Neovascular AMD is sometimes referred to as the "wet" form of AMD. The purpose of this Phase 1 clinical research study is to examine the safety and ability of an experimental study drug to treat a complication of the disease which leads to vision loss. The name of the study drug is "AAV2-sFLT01." This experimental study drug uses a virus to transfer a gene (genetic code) into cells within the eye. The gene codes for a protein that is intended to diminish the growth of abnormal blood vessels under the retina. The duration of the gene's effect is currently unknown, but might last for years.

This clinical research study will look at the safety of a single administration of AAV2-sFLT01 injected directly into the eye. There are 2 parts to this study, but patients will take part in only one of them. In the first part of the study, 4 different doses of the study drug will be studied in 4 separate groups of patients. Patients in the first part of the study will not be randomized. In the second part of the study, the highest dose that was safe and well tolerated will be studied in 10 more patients. Patients in this part of the study may have a ranibizumab (Lucentis®) injection 26 weeks after their AAV2-sFLT01 injection to verify their responsiveness to anti-VEGF therapy, if they have not demonstrated a response to AAV2-sFLT01. The initial two parts of this protocol are expected to be completed in July, 2013.

All patients injected with AAV2-sFLT01 will be asked to participate in an Extended Follow-Up (EFU) program for up to an additional 4 years. Participation is voluntary but strongly encouraged as it allows for the long term collection of safety information as well as information about the potential long term effects of the study drug. Study visits will take place at the site every 6 months.

Up to thirty-four (34) patients at multiple centers will take part in this study in the United States.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Choroidal neovascular membrane (CNV) secondary to AMD, as confirmed by the patient's medical history and a documented diagnosis of CNV.
Distance BCVA of 20/100 or worse in the study eye.
Subfoveal disciform scarring for the first part of the study (the dose-escalation part). Patients must not have subfoveal disciform scarring in the second part of the study (the maximum tolerated dose part). In addition, patients enrolled in the second part of the study must have demonstrated responsiveness to ranibizumab (Lucentis®) or bevacizumab (Avastin™) within 12 months prior to screening and after the patient's most recent treatment of anti-VEGF therapy.
Noted presence of intra- or sub-retinal fluid.
Adequate dilation of pupils to permit thorough ocular examination and testing.
Must be willing to have samples of anterior chamber fluid collected from the study eye.

Exclusion Criteria:

CNV in the study eye due to any reason other than AMD.
History of conditions in the study eye during Screening which might alter visual acuity or interfere with study testing.
Active uncontrolled glaucoma.
Had any intraocular surgeries in the study eye within 3 months of enrollment or are known or likely candidates for intraocular surgery (including cataract surgery) in the study eye within 1 year of treatment.
Acute or chronic infection in the study eye.
History of inflammation in the study eye or ongoing inflammation in either eye.
Any contraindication to intravitreal injection.
Received Photo Dynamic Therapy in the study eye within 60 days, or laser photocoagulation within 14 days prior to Screening.
Currently using or have used ranibizumab (Lucentis®), bevacizumab (Avastin™), or pegaptanib sodium (Macugen®) within 1 month prior to Screening.
Currently using or have used Aflibercept (Eylea®) within 4 months prior to Screening.
Currently using any periocular (study eye), intravitreal (study eye), or systemic (oral or intravenous) steroids within 3 months prior to Screening.
Any active herpetic infection, in particular active lesions in the eye or on the face.
Any significant poorly controlled illness that would preclude study compliance and follow-up.
Current or prior use of any medication known to be toxic to the retina or optic nerve.
Previous treatment with any ocular or systemic gene transfer product.
Received any investigational product within 120 days prior to Screening.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024998

Contacts

Contact: Medical Information	800-745-4447	medinfo@genzyme.com
Contact: Medical Information	617-252-7832	medinfo@genzyme.com

Locations

United States, Arizona
Retinal Consultants of AZ	Recruiting
Phoenix, Arizona, United States
United States, Maryland
Johns Hopkins University School of Medicine	Recruiting
Baltimore, Maryland, United States
United States, Massachusetts
Ophthalmic Consultants of Boston	Recruiting
Boston, Massachusetts, United States
University of Massachusetts Medical School	Recruiting
Worcester, Massachusetts, United States

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT01024998 History of Changes
Other Study ID Numbers:	sFLT01-AMD-00106, 0810-948
Study First Received:	December 2, 2009
Last Updated:	April 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genzyme:

Age-Related Macular Degeneration
AMD
Wet AMD
Neovascular AMD

Ocular
Ocular gene therapy
Subretinal neovascularization

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 May 23, 2012