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

August 21, 2018 updated by: Genzyme, a Sanofi Company

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287-9277
        • investigational site number 03WilmerEy
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • investigational site number 02Ophthalm
      • Worcester, Massachusetts, United States, 01605
        • investigational site number 01UMassMem
    • New York
      • Slingerlands, New York, United States, 85014
        • investigational site number 05RetinaCo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.
  • The fellow eye must have distance BCVA of 20/400 or better.
  • The study eye, i.e., the eye that receives investigational product, has the worst CVA (As compared to the fellow eye).
  • Subfoveal disciform scarring in the study eye for the first part of the study (the dose-escalation part). Patients may or may not have macular scarring in the study eye for the second part of the study (MTD phase). In addition, patients enrolled in the second part of the study must have demonstrated responsiveness to an anti-VEGF therapy 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.
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.
Experimental: 2 x 10^9 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.
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.
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.
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.
Experimental: 6 x 10^9 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.
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.
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.
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.
Experimental: 2 x 10^10 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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
Time of treatment through Week 52 (referred to as the "core" study)
Number of Treatment Emergent Adverse Events
Time Frame: Time of treatment through Week 52 (referred to as the "core" study)
Time of treatment through Week 52 (referred to as the "core" study)
Number of Treatment Emergent Adverse Events
Time Frame: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)
Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)

Secondary Outcome Measures

Outcome Measure
Time Frame
Decreased retinal thickness
Time Frame: Time of treatment through Week 52 (referred to as the "core" study)
Time of treatment through Week 52 (referred to as the "core" study)
Decreased retinal thickness
Time Frame: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)
Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 11, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2018

Study Registration Dates

First Submitted

December 2, 2009

First Submitted That Met QC Criteria

December 2, 2009

First Posted (Estimate)

December 3, 2009

Study Record Updates

Last Update Posted (Actual)

August 22, 2018

Last Update Submitted That Met QC Criteria

August 21, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • sFLT01-AMD-00106
  • 0810-948 (Other Identifier: NIH Office of Biotechnology Activities)
  • MSC12870 (Other Identifier: Sanofi)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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