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

June 23, 2014 updated by: Ahmad Mansour, MD, Clinical Professor, AUB, Rafic Hariri University Hospital

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

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..)

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Lebanon
      • Beirut, Lebanon
        • Recruiting
        • Rafic Hariri University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 95 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • Zaltrap

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years
OCT retinal structure
Time Frame: 2 years
OCT, visual acuity measure, inflammation measure
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rafic Hariri University Hospital

Investigators

  • Study Chair: Ahmad Mansour, MD, RHUH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (ANTICIPATED)

September 1, 2016

Study Completion (ANTICIPATED)

December 1, 2016

Study Registration Dates

First Submitted

June 14, 2014

First Submitted That Met QC Criteria

June 23, 2014

First Posted (ESTIMATE)

June 25, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

June 25, 2014

Last Update Submitted That Met QC Criteria

June 23, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INV 2014-194

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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