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Ziv-aflibercept in Eyes With Retinal Diseases and Poor Vision-phase I (ZIV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02173873
Recruitment Status : Unknown
Verified June 2014 by Ahmad Mansour, MD, Clinical Professor, AUB, Rafic Hariri University Hospital.
Recruitment status was:  Recruiting
First Posted : June 25, 2014
Last Update Posted : June 25, 2014
Information provided by (Responsible Party):
Ahmad Mansour, MD, Clinical Professor, AUB, Rafic Hariri University Hospital

Brief Summary:
Aflibercept is FDA approved and the same molecule is available as hyperosmolar for oncology (cost 800 USD for 4ml) and isoosmolar for Ophthalmology (cost 1,770 USD for 0.05ml injection). The 4ml bottle can be fractionated to be used in 40 patients hence the 0.05 ml injection would cost 20 USD for patients. Animal studies showed the injection is safe, knowing that the rabbit vitreous volume is 3-4 times smaller than the human eye. Our pilot study is to ascertain if the approved molecule for oncology when injected in the eye is safe as it is diluted into 5ml vitreous (100 times dilution). If this is so then we can save the patient 100 times for the most efficient antiVEGF that is used for maculopathy in various diseases (AMD, DME, CRVO, etc..)

Condition or disease Intervention/treatment Phase
Age Related Macular Degeneration Central Retinal Vein Occlusion Drug: ziv-aflibercept drug Phase 1

Detailed Description:

Protocol Inject 0.05 ml of zaltrap coumpounded in a sterile way into the vitreous of blind eyes (vision less than 20/100) with various diseases of the retina that require antiVEGF therapy after patient consent. Vision will be monitored 15 minutes, 1 day and 1 week after injection. SD-OCT will be performed before and after 1 week to look for possible side effects.

The safety and efficacy of Eylea in the treatment of macular edema following CRVO3,4 were assessed in 2 randomized, multicenter, double-masked, sham-controlled studies: COPERNICUS and GALILEO. A total of 358 patients were treated and evaluable for efficacy (217 with Eylea) in the two studies. In both, patients were randomly assigned in a 3:2 ratio to either 2 mg Eylea administered every 4 weeks, or sham injections (control group) administered every 4 weeks for a total of 6 injections. After 6 monthly injections, patients continued to receive Eylea treatment during weeks 24 to 52 only if they met pre-specified retreatment criteria (PRN), except for patients in the sham control group in the GALILEO study who continued to receive sham injections through week 52. In the COPERNICUS study, after 6 months, 56% of patients receiving Eylea 2 mg monthly gained at least 15 letters of BCVA from baseline, as measured by ETDRS, compared to 12% of patients receiving sham injections (p<0.01), the primary endpoint of the study. Patients receiving Eylea 2 mg monthly gained, on average, 17.3 letters of vision compared to a mean loss of 4.0 letters with sham control injections (p<0.01), a secondary endpoint.

Ziv-aflibercept or zaltrap6 (Sanofi-Aventis US, LLC, Bridgewater, NJ/Regeneron Pharmaceuticals, Inc, Tarrytown, NY) is FDA approved for the treatment of metastatic colorectal cancer. During Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration February 2014 conference, Michel Eid Farah, João R. Dias, Fernando M. Penha, and Eduardo B. Rodrigues investigated the safety of ziv-aflibercept in vitro and in vivo. In vitro toxicity was verified using ARPE-19 cultured cells exposed to anti-angiogenic vs balanced salt solution (BSS) for 10 minutes. Viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which evaluates cell viability by mitochondrial activity. No signs of cell toxicity were observed, and cell viability was similar for ziv-aflibercept, aflibercept, and BSS. For the in vivo study, they tested 1 injection of 0.05 mL ziv-aflibercept vs aflibercept in the right eyes of 18 rabbits, 9 eyes in each group. BSS was injected in the fellow eyes and served as control. After the injections, all animals were examined by funduscopy, SD-OCT), and ERG at baseline, 24 hours, and 7 days. Aqueous, vitreous, and serum samples were collected at baseline, 24 hours, and 7 days for pH and osmolarity analysis. The animals were sacrificed and the eyes were enucleated for morphologic study by light and electron microscopy. No abnormalities were found at 24 hours or 7 days after intravitreal injection of either drug when assessed by fundus exam and SD-OCT, ERG, and histology as well as transmission microscopy. There were also no changes in osmolarity in the aqueous humor or vitreous samples in any group after 24 hours and 1 week.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ziv-aflibercept in Eyes With Eyes With Retinal Diseases and Poor Vision-phase I
Study Start Date : June 2014
Estimated Primary Completion Date : September 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: one injection of ziv aflibercept intravitreal route
Intervention: Inject 0.05 ml of zaltrap into the vitreous of blind eyes with various diseases (AMD, CRVO) and monitor vision and OCT 1 day and 1 week after injection
Drug: ziv-aflibercept drug
intravitreal injection of ziv-ablicerpt in one eye of each patient with retinal disease and poor vision
Other Name: Zaltrap

Primary Outcome Measures :
  1. Ziv-aflibercept in retinal diseases with poor vision: Safety monitoring by OCT and visual acuity [ Time Frame: 2 years ]
    anterior chamber, vitreous, lens, retina exam PLUS OCT and visual acuity

  2. OCT retinal structure [ Time Frame: 2 years ]
    OCT, visual acuity measure, inflammation measure

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 95 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: Eyes with wet age related macular degeneration, central retinal vein occlusion or diseases that require antiVEGF especially in poor vision eyes -

Exclusion Criteria: eyes that had recent eye surgery, inability to sign consent, blepharitis, conjunctivitis


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02173873

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Contact: Ahmad Mansour, MD 9613377633
Contact: Muhammad Yunis, MD 9613641055

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Rafic Hariri University Hospital Recruiting
Beirut, Lebanon
Contact: Ahmad Mansour, MD    9613377633   
Sub-Investigator: Muhammad Younis, MD         
Principal Investigator: Ahmad Mansour, MD         
Sponsors and Collaborators
Rafic Hariri University Hospital
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Study Chair: Ahmad Mansour, MD RHUH
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Ahmad Mansour, MD, Clinical Professor, AUB, Chair, Department of Opthalmology, Rafic Hariri Hospital, Rafic Hariri University Hospital Identifier: NCT02173873    
Other Study ID Numbers: INV 2014-194
First Posted: June 25, 2014    Key Record Dates
Last Update Posted: June 25, 2014
Last Verified: June 2014
Keywords provided by Ahmad Mansour, MD, Clinical Professor, AUB, Rafic Hariri University Hospital:
Age related macular degeneration
central retinal vein occlusion
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Vein Occlusion
Retinal Diseases
Retinal Degeneration
Eye Diseases
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases