Macular DegenerationPhase 1/2AMDNCT01494805
Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration
A Phase 1/2 study testing rAAV.sFlt-1 in people with Macular Degeneration and Age-related Maculopathies, run by Lions Eye Institute, Perth, Western Australia at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy
- What is being tested?
- rAAV.sFlt-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteAustralia
- Study dates
- Dec 2011to Aug 2017
- Phase
- Phase 1/2
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy, Maculopathies,Age-related, Maculopathy,Age-related, Retinal Degeneration
- Being tested
- rAAV.sFlt-1, Control (ranibizumab alone)
- 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
- Medical subject headings
- Macular Degeneration, Retinal Degeneration, Retinal Neovascularization, Eye Diseases, Wet Macular Degeneration, Retinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV.sFlt-1Biological
1 x 10^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
rAAV.sFlt-1Biological
1 x 10^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection
Control (ranibizumab alone)Other
Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).
| Study group | Role | What they receive |
|---|---|---|
| Low Dose rAAV.sFlt-1 | Experimental | Not described Receives: Biological: rAAV.sFlt-1 |
| High Dose rAAV.sFlt-1 | Experimental | Not described Receives: Biological: rAAV.sFlt-1 |
| Control - ranibizumab only | Active comparator | Not described Receives: Other: Control (ranibizumab alone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Primary endpoint at 1 month
Secondary outcomes (1)
Maintenance or improvement of vision without the necessity of ranibizumab re-injections
- Best-corrected visual acuity
- CNV lesion
- Foveal thickness
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionMay 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lions Eye Institute, Perth, Western Australia
- Sponsor type
- University, hospital or other
- Collaborators
- Adverum Biotechnologies, Inc.
- Responsible party
- Principal investigator, Prof. P. Elizabeth Rakoczy, Lions Eye Institute, Perth, Western Australia
- Investigators
- Ian Constable, Professor, Principal investigator, Lions Eye Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494805
- Sponsor's protocol ID
- 2008-135
- Acronym
- AMD
- Status last verified
- Aug 2017
- First submitted
- 14 Dec 2011
- Last updated
- 1 Sep 2017
- 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 39207600Constable 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.
PubMed 27865764Rakoczy 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.
PubMed 26431823
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01494805
- Acronym / sponsor ID
- AMD / 2008-135
- Conditions
- Macular Degeneration, Age-related Maculopathies, Age-related Maculopathy, Maculopathies,Age-related, Maculopathy,Age-related, Retinal Degeneration
- Keywords
- Age-related Macular Degeneration, AAV, AMD, Wet AMD, Neovascular AMD, Gene Therapy, Ocular, Ocular Gene Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Lions Eye Institute, Perth, Western AustraliaUniversity, hospital or other
- Collaborators
- Adverum Biotechnologies, Inc.
- Study start
- Dec 2011 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 19 Dec 2011 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose rAAV.sFlt-1 | Experimental | Biological: rAAV.sFlt-1 |
| High Dose rAAV.sFlt-1 | Experimental | Biological: rAAV.sFlt-1 |
| Control - ranibizumab only | Active comparator | Other: Control (ranibizumab alone) |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (4 listed)
- 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;
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 |
|---|---|---|
| rAAV.sFlt-11 x 10^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection | Biological | Low Dose rAAV.sFlt-1 |
| rAAV.sFlt-11 x 10^11 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection | Biological | High Dose rAAV.sFlt-1 |
| Control (ranibizumab alone)Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis). | Other | Control - ranibizumab only |
Primary outcome
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
1. Ocular examination: * Ocular inflammation * Intraocular pressure * Visual acuity * Retinal bleeding 2. Abnormal laboratory data
1 secondary outcome
Maintenance or improvement of vision without the necessity of ranibizumab re-injections
Time frame: Up to 3 years
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 1 Sep 2017.
- 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 27865764Constable 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.
- Derived from this study: PubMed 26431823Rakoczy 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.
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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.
Ian Constable, Professor principal investigator
Lions Eye Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rAAV.sFlt-1 in people with Macular Degeneration and Age-related Maculopathies, run by Lions Eye Institute, Perth, Western Australia at 1 site in Australia.
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 7 inclusion and 4 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 1 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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). 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 NCT01494805, which also lists 3 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 1 Sep 2017.