Macular DegenerationPhase 1NCT01024998
Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)
A Phase 1 study testing AAV2-sFLT01 in people with Macular Degeneration and Age-Related Maculopathies, run by Genzyme, a Sanofi Company at 4 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Macular Degeneration, Age-Related Maculopathies, Age-Related Maculopathy
- What is being tested?
- AAV2-sFLT01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 4 sitesUnited States
- Study dates
- 11 Jan 2010to Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
investigational site number 03WilmerEy
Baltimore, Maryland, 21287-9277
investigational site number 02Ophthalm
Boston, Massachusetts, 02114
investigational site number 05RetinaCo
Slingerlands, New York, 85014
investigational site number 01UMassMem
Worcester, Massachusetts, 01605
About this study
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
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).
Read the 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.
- Conditions
- Macular Degeneration, Age-Related Maculopathies, Age-Related Maculopathy, Maculopathies, Age-Related, Maculopathy, Age-Related, Retinal Degeneration
- Being tested
- AAV2-sFLT01
- Keywords
- Age-Related Macular Degeneration, AMD, Wet AMD, Neovascular AMD, Ocular, Ocular gene therapy, Subretinal neovascularization
- Medical subject headings
- Macular Degeneration, Retinal Degeneration, Retinal Neovascularization, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV2-sFLT01Biological
2 x 10^8 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
AAV2-sFLT01Biological
2 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
AAV2-sFLT01Biological
6 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
AAV2-sFLT01Biological
2 x 10^10 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
| Study group | Role | What they receive |
|---|---|---|
| 2 x 10^8 vector genomes (vg) AAV2-sFLT01 | Experimental | Not described Receives: Biological: AAV2-sFLT01 |
| 2 x 10^9 vector genomes (vg) AAV2-sFLT01 | Experimental | Not described Receives: Biological: AAV2-sFLT01 |
| 6 x 10^9 vector genomes (vg) AAV2-sFLT01 | Experimental | Not described Receives: Biological: AAV2-sFLT01 |
| 2 x 10^10 vector genomes (vg) AAV2-sFLT01 | Experimental | Not described Receives: Biological: AAV2-sFLT01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of a single uniocular intravitreal injection of AAV2-sFLT01
Measured: Time of treatment through Week 52 (referred to as the "core" study)
Number of Treatment Emergent Adverse Events
Measured: Time of treatment through Week 52 (referred to as the "core" study)
Number of Treatment Emergent Adverse Events
Measured: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)
Secondary outcomes (2)
Decreased retinal thickness
Measured: Time of treatment through Week 52 (referred to as the "core" study)
Decreased retinal thickness
Measured: Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2009 (estimated)
- Study start11 Jan 2010
- Primary completionJul 2014
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01024998
- Sponsor's protocol ID
- sFLT01-AMD-00106
- Other IDs
- 0810-948, MSC12870
- Status last verified
- Aug 2018
- First submitted
- 2 Dec 2009
- Last updated
- 22 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wazan LE, Widhibrata A, Liu GS. Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications. Angiogenesis. 2024 Nov;27(4):641-661. doi: 10.1007/s10456-024-09942-8. Epub 2024 Aug 29.
PubMed 39207600Heier JS, Kherani S, Desai S, Dugel P, Kaushal S, Cheng SH, Delacono C, Purvis A, Richards S, Le-Halpere A, Connelly J, Wadsworth SC, Varona R, Buggage R, Scaria A, Campochiaro PA. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial. Lancet. 2017 Jul 1;390(10089):50-61. doi: 10.1016/S0140-6736(17)30979-0. Epub 2017 May 17.
PubMed 28526489
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01024998
- Acronym / sponsor ID
- sFLT01-AMD-00106
- Conditions
- Macular Degeneration, Age-Related Maculopathies, Age-Related Maculopathy, Maculopathies, Age-Related, Maculopathy, Age-Related, Retinal Degeneration
- Keywords
- Age-Related Macular Degeneration, AMD, Wet AMD, Neovascular AMD, Ocular, Ocular gene therapy, Subretinal neovascularization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2010 (actual)
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 3 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 2 x 10^8 vector genomes (vg) AAV2-sFLT01 | Experimental | Biological: AAV2-sFLT01 |
| 2 x 10^9 vector genomes (vg) AAV2-sFLT01 | Experimental | Biological: AAV2-sFLT01 |
| 6 x 10^9 vector genomes (vg) AAV2-sFLT01 | Experimental | Biological: AAV2-sFLT01 |
| 2 x 10^10 vector genomes (vg) AAV2-sFLT01 | Experimental | Biological: AAV2-sFLT01 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV2-sFLT012 x 10^8 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL. | Biological | 2 x 10^8 vector genomes (vg) AAV2-sFLT01 |
| AAV2-sFLT012 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL. | Biological | 2 x 10^9 vector genomes (vg) AAV2-sFLT01 |
| AAV2-sFLT016 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL. | Biological | 6 x 10^9 vector genomes (vg) AAV2-sFLT01 |
| AAV2-sFLT012 x 10^10 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL. | Biological | 2 x 10^10 vector genomes (vg) AAV2-sFLT01 |
Primary outcome
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)
Number of Treatment Emergent Adverse Events
Time frame: 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)
2 secondary outcomes
Decreased retinal thickness
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2018.
- Derived from this study: PubMed 39207600Wazan LE, Widhibrata A, Liu GS. Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications. Angiogenesis. 2024 Nov;27(4):641-661. doi: 10.1007/s10456-024-09942-8. Epub 2024 Aug 29.
- Derived from this study: PubMed 28526489Heier JS, Kherani S, Desai S, Dugel P, Kaushal S, Cheng SH, Delacono C, Purvis A, Richards S, Le-Halpere A, Connelly J, Wadsworth SC, Varona R, Buggage R, Scaria A, Campochiaro PA. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial. Lancet. 2017 Jul 1;390(10089):50-61. doi: 10.1016/S0140-6736(17)30979-0. Epub 2017 May 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AAV2-sFLT01 in people with Macular Degeneration and Age-Related Maculopathies, run by Genzyme, a Sanofi Company at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01024998, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2018.