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Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

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ClinicalTrials.gov Identifier: NCT01024998
Recruitment Status : Completed
First Posted : December 3, 2009
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE December 2, 2009
First Posted Date  ICMJE December 3, 2009
Last Update Posted Date August 22, 2018
Actual Study Start Date  ICMJE January 11, 2010
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2011)
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 2, 2009)
Maximum tolerated dose of a single uniocular intravitreal injection of AAV2-sFLT01 [ Time Frame: Time of treatment through Week 52 ]
Change History Complete list of historical versions of study NCT01024998 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2011)
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2009)
Decreased retinal thickness [ Time Frame: Time of treatment through Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)
Official Title  ICMJE 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
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Macular Degeneration
  • Age-Related Maculopathies
  • Age-Related Maculopathy
  • Maculopathies, Age-Related
  • Maculopathy, Age-Related
  • Retinal Degeneration
  • Retinal Neovascularization
  • Gene Therapy
  • Therapy, Gene
  • Eye Diseases
Intervention  ICMJE
  • Biological: AAV2-sFLT01
    2 x 10^8 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
  • Biological: AAV2-sFLT01
    2 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
  • Biological: AAV2-sFLT01
    6 x 10^9 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
  • Biological: AAV2-sFLT01
    2 x 10^10 vector genomes (vg) AAV2-sFLT01. Single intravitreal injection to a single eye, using a fixed volume of 100 μL.
Study Arms  ICMJE
  • Experimental: 2 x 10^8 vector genomes (vg) AAV2-sFLT01
    Intervention: Biological: AAV2-sFLT01
  • Experimental: 2 x 10^9 vector genomes (vg) AAV2-sFLT01
    Intervention: Biological: AAV2-sFLT01
  • Experimental: 6 x 10^9 vector genomes (vg) AAV2-sFLT01
    Intervention: Biological: AAV2-sFLT01
  • Experimental: 2 x 10^10 vector genomes (vg) AAV2-sFLT01
    Intervention: Biological: AAV2-sFLT01
Publications * 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. Erratum in: Lancet. 2017 Jul 1;390(10089):28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 26, 2015)
19
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2009)
34
Actual Study Completion Date  ICMJE July 2018
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Received any investigational product within 120 days prior to Screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01024998
Other Study ID Numbers  ICMJE sFLT01-AMD-00106
0810-948 ( Other Identifier: NIH Office of Biotechnology Activities )
MSC12870 ( Other Identifier: Sanofi )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Sanofi
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP