Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration

NCT01494805 | Completed Phase 1 DMC

• 1 other identifier: 2008-135
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Macular Degeneration; Age-related Maculopathies; Age-related Maculopathy; Maculopathies,Age-related; Maculopathy,Age-related; Retinal Degeneration; Retinal Neovascularization; Eye Diseases

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

Outcome Measures

Primary Outcomes (1)

• No sign of unresolved ophthalmic complications, toxicity or systemic complications as measured by laboratory tests from 1 month post injection

  1. Ocular examination: * Ocular inflammation * Intraocular pressure * Visual acuity * Retinal bleeding 2. Abnormal laboratory data

  Primary endpoint at 1 month

Secondary Outcomes (1)

• Maintenance or improvement of vision without the necessity of ranibizumab re-injections

  Up to 3 years

Study Arms (3)

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)

Interventions

rAAV.sFlt-1 BIOLOGICAL

1 x 10\^10 vector genomes (vg) rAAV.sFlt-1, delivered by subretinal injection

Low Dose rAAV.sFlt-1

Control (ranibizumab alone) OTHER

Patients will not receive rAAV.sFlt-1, but will be eligible for retreatment with ranibizumab (Lucentis).

Control - ranibizumab only

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Lions Eye Institute, Perth, Western Australia: lead
• Adverum Biotechnologies, Inc.: collaborator

Study Sites (1)

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (2)

• Constable 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.

  PMID: 27865764 DERIVED

• Rakoczy 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.

  PMID: 26431823 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Retinal Degeneration; Retinal Neovascularization; Eye Diseases; Wet Macular Degeneration; Retinal Diseases

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ian Constable, Professor

  Lions Eye Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Scientific Investigator

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: December 19, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2017
• Study Completion: August 1, 2017
• Last Updated: September 1, 2017

Record last verified: 2017-08

Locations

AU (1)