Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

NCT01072357 | Completed Phase 1 Results DMC

• 1 other identifier: 09-07-062
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The leading risk factor for corneal transplant rejection is abnormal blood vessel growth of the host bed. Vascular endothelial growth factor (VEGF) is thought to be a mediator of this corneal neovascularization (NV), therefore we would like to test the safety and efficacy of local VEGF blockade in the promotion of graft survival in high risk corneal transplants.

Conditions

Corneal Neovascularization; Corneal Graft Failure

Keywords

High-Risk Corneal Transplantation; Penetrating Keratoplasty; Neovascularization; Corneal Blood Vessels; Avastin; Bevacizumab; Corneal Graft

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Graft Failure at Week 39 and 52

  Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.

  12 months

Secondary Outcomes (1)

• Endothelial Cell Density

  52 Weeks

Study Arms (2)

Avastin® (bevacizumab)

ACTIVE COMPARATOR

Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 milliliter (mL) (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical bevacizumab (1% solution). Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule.

Drug: Avastin® (bevacizumab)

0.9% NaCl & Refresh Liquigel

PLACEBO COMPARATOR

Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% sodium chloride (NaCl). Starting Day 1 post-transplant surgery, subjects will begin treatment with topical Refresh Liquigel. Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments (both topical and subconjunctival injection) are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule.

Drug: 0.9% NaCl & Refresh Liquigel

Interventions

Avastin® (bevacizumab) DRUG

One time subconjunctival injection of 0.1 mL (2.5 mg) bevacizumab followed by topical treatment with 1% solution bevacizumab four times a day for four weeks.

Also known as: Avastin, bevacizumab

Avastin® (bevacizumab)

0.9% NaCl & Refresh Liquigel DRUG

One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks

Also known as: Sodium Chloride, Refresh Liquigel, NaCL

0.9% NaCl & Refresh Liquigel

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Patient or legally authorized representative willing and able to provide written informed consent
• Willing and able to comply with study assessments for the full duration of the study
• High-risk characteristics for penetrating keratoplasty: Either presence of 1.) Corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR 2.) Extension of corneal NV to graft-host junction in a previous failed graft
• In generally good stable overall health

You may not qualify if:

• History of Stevens-Johnson syndrome or ocular pemphigoid
• Ocular or periocular malignancy
• Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
• Uncontrolled glaucoma
• Currently on dialysis
• Has received treatment with anti-VEGF agents (intraocular or systemic) within 45 days of study entry
• Concurrent use of systemic anti-VEGF agents
• Change in topical corticosteroid regimen within 14 days of transplantation
• Use of systemic immunosuppressive for indication other than corneal graft rejection
• Pregnancy (positive pregnancy test) or lactating
• Pre-menopausal women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
• Uncontrolled hypertension defined as systolic blood pressure (BP) ≥150 or diastolic BP ≥90 mmHg
• History of thromboembolic event within 12 months prior to study entry
• Participation in another simultaneous medical investigation or trial

Sponsors & Collaborators

• Reza Dana, MD: lead

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Corneal Neovascularization; Neovascularization, Pathologic

Interventions

Bevacizumab; Carboxymethylcellulose Sodium; Sodium Chloride

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; 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; Methylcellulose; Cellulose; Glucans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Reza Dana
• Organization: Massachusetts Eye and Ear

Reza_Dana@meei.harvard.edu

617-573-4431

Study Officials

• Reza Dana, MD, MPH, MSc

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 18, 2010
• First Posted: February 22, 2010
• Study Start: December 1, 2009
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: June 15, 2018
• Results First Posted: May 15, 2017

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)