NCT01024998

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2010

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 2, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 3, 2009

Completed
1 month until next milestone

Study Start

First participant enrolled

January 11, 2010

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2018

Completed
Last Updated

August 22, 2018

Status Verified

August 1, 2018

Enrollment Period

4.5 years

First QC Date

December 2, 2009

Last Update Submit

August 21, 2018

Conditions

Macular DegenerationAge-Related MaculopathiesAge-Related MaculopathyMaculopathies, Age-RelatedMaculopathy, Age-RelatedRetinal DegenerationRetinal NeovascularizationGene TherapyTherapy, GeneEye Diseases

Keywords

Age-Related Macular DegenerationAMDWet AMDNeovascular AMDOcularOcular gene therapySubretinal neovascularization

Outcome Measures

Primary Outcomes (3)

  • Maximum tolerated dose of a single uniocular intravitreal injection of AAV2-sFLT01

    Time of treatment through Week 52 (referred to as the "core" study)

  • Number of Treatment Emergent Adverse Events

    Time of treatment through Week 52 (referred to as the "core" study)

  • Number of Treatment Emergent Adverse Events

    Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)

Secondary Outcomes (2)

  • Decreased retinal thickness

    Time of treatment through Week 52 (referred to as the "core" study)

  • Decreased retinal thickness

    Up to 4 years after the "core" study (referred to as the "Extended Follow-up" period)

Study Arms (4)

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

Interventions

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.

2 x 10^8 vector genomes (vg) AAV2-sFLT01

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

investigational site number 03WilmerEy

Baltimore, Maryland, 21287-9277, United States

Location

investigational site number 02Ophthalm

Boston, Massachusetts, 02114, United States

Location

investigational site number 01UMassMem

Worcester, Massachusetts, 01605, United States

Location

investigational site number 05RetinaCo

Slingerlands, New York, 85014, United States

Location

Related Publications (1)

  • Heier 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.

    PMID: 28526489DERIVED

MeSH Terms

Conditions

Macular DegenerationRetinal DegenerationRetinal NeovascularizationEye Diseases

Condition Hierarchy (Ancestors)

Retinal DiseasesEye Diseases, HereditaryNeovascularization, PathologicMetaplasiaPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Medical Monitor

    Genzyme, a Sanofi Company

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 2, 2009

First Posted

December 3, 2009

Study Start

January 11, 2010

Primary Completion

July 1, 2014

Study Completion

July 1, 2018

Last Updated

August 22, 2018

Record last verified: 2018-08

Locations

US(4)