Evidence map›Paper›PMID 27865764›Full record

Trial reportEBioMedicine2016

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration.

Ian J Constable, Cora M Pierce, Chooi-May Lai, Aaron L Magno, Mariapia A Degli-Esposti, Martyn A French, Ian L McAllister, Steve Butler, Samuel B Barone, Steven D Schwartz and 2 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01494805 (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), which is not on this map. Cited by 90 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01494805 phase1 / phase2completednot on this map

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)

TypeinterventionalSponsorLions Eye Institute, Perth, Western AustraliaRan2011 to 2017Enrolled40ConditionsMacular Degeneration, Age-related Maculopathies, Age-related Maculopathy, Maculopathies,Age-relatedArmsrAAV.sFlt-1, Control (ranibizumab alone)
3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Animal Models of Choroidal Neovascularization: A Systematic Review.Investigative ophthalmology & visual science · 2022
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Article
  8. Review
  9. Article
  10. VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  16. Article
  17. The ambition for a one-and-done vision-saving AAV vector.Molecular therapy. Methods & clinical development · 2025
    Article
  18. Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  19. Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  20. Article

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ian J ConstableLions Eye Institute, Nedlands, WA, Australia; Sir Charles Gairdner Hospital, Nedlands, WA, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia.
Cora M PierceLions Eye Institute, Nedlands, WA, Australia.
Chooi-May LaiLions Eye Institute, Nedlands, WA, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia.
Aaron L MagnoLions Eye Institute, Nedlands, WA, Australia.
Mariapia A Degli-EspostiLions Eye Institute, Nedlands, WA, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia.
Martyn A FrenchSchool of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia; Department of Clinical Immunology, The University of Western Australia, Crawley, WA, Australia.
Ian L McAllisterLions Eye Institute, Nedlands, WA, Australia; Sir Charles Gairdner Hospital, Nedlands, WA, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia.
Steve ButlerAvalanche Biotechnologies, Inc., Menlo Park, CA, USA.
Samuel B BaroneAvalanche Biotechnologies, Inc., Menlo Park, CA, USA.
Steven D SchwartzUniversity of California Los Angeles, CA, USA.
Mark S BlumenkranzByers Eye Institute, Stanford Department of Ophthalmology, Palo Alto, CA, USA.
Elizabeth P RakoczyLions Eye Institute, Nedlands, WA, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia. Electronic address: Elizabeth.rakoczy@uwa.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe present the results of a Phase 2a randomized controlled trial investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene therapy in patients with active wet age-related macular degeneration (wAMD).

methodsAll patients (n=32), (ClinicalTrials.gov; NCT01494805), received ranibizumab injections at baseline and week 4, and thereafter according to prespecified criteria. Patients in the gene therapy group (n=21) received rAAV.sFLT-1 (1×10

findingsOcular adverse events (AEs) in the rAAV.sFLT-1 group were mainly procedure related and self-resolved. All 11 phakic patients in the rAAV.sFLT-1 group showed progression of cataract following vitrectomy. No systemic safety signals were observed and none of the serious AEs were associated with rAAV.sFLT-1. AAV2 capsid was not detected and rAAV.sFLT-1 DNA was detected transiently in the tears of 13 patients. ELISPOT analysis did not identify any notable changes in T-cell response. In the rAAV.sFLT-1 group 12 patients had neutralizing antibodies (nAb) to AAV2. There was no change in sFLT-1 levels in bodily fluids. In the rAAV.sFLT-1 group, Best Corrected Visual Acuity (BCVA) improved by a median of 1.0 (IQR: -3.0 to 9.0) Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline compared to a median of -5.0 (IQR: -17.5 to 1.0) ETDRS letters change in the control group. Twelve (57%) patients in the rAAV.sFLT-1 group maintained or improved vision compared to 4 (36%) in the control group. The median number of ranibizumab retreatments was 2.0 (IQR: 1.0 to 6.0) for the gene therapy group compared to 4.0 (IQR: 3.5 to 4.0) for the control group. Interpretation rAAV.sFLT-1 combined with the option for co-treatment appears to be a safe and promising approach to the treatment of wAMD.

fundingNational Health and Medical Research Council of Australia (AP1010405), Lions Eye Institute, Perth Australia, Avalanche Biotechnologies, Menlo Pk, CA, USA.

Indexed as

Genetic TherapyAgedAged, 80 and overCase-Control StudiesCombined Modality TherapyDependovirusFemaleGenetic VectorsHumansMaleRanibizumabRetinaTissue DistributionTomography, Optical CoherenceTreatment OutcomeVascular Endothelial Growth Factor Receptor-1FLT1 protein, humanRanibizumabVascular Endothelial Growth Factor Receptor-1AAV.sFLT-1Clinical trialGene therapyWet age related macular degeneration

Identifiers

PMID27865764
PMCPMC5161436

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.