A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

NCT01996826 | Completed Phase 1 Results DMC

• 1 other identifier: 13-113H
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to investigate whether using bevacizumab (Avastin®) is both safe and effective at decreasing the likelihood of a high-risk corneal graft rejection. Patients who are "high-risk" for rejection have blood vessels growing from the white of the eye into the cornea (clear, front region of the eye). The medication is used at the time of surgery and in the weeks following surgery. Participants have a 50/50 chance at receiving the active study medication or a placebo medication.

Conditions

Corneal Neovascularization; Corneal Graft Failure

Keywords

Corneal Neovascularization; Cornea Blood Vessels; Corneal Graft Failure; High-Risk Penetrating Keratoplasty; Corneal Transplant

Outcome Measures

Primary Outcomes (3)

• Endothelial Rejection Rate

  Endothelial rejection rates in patients in the treatment group and the control group were calculated using the Kaplan-Meier survival curve. The Kaplan-Meier/product limit estimator is a non-parametric statistical test used to show the probability of an event occurring at a given time interval. The Kaplan-Meier estimator is used to show what the probability of corneal transplant rejection (and therefore transplant survival) after administration of the active treatment or control.

  12 Months

• Number of Participants Experiencing Ocular Adverse Events

  Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).

  12 months

• Incidence of Systemic Adverse Events

  Incidence and severity of systemic adverse events during the study (based on physical examination, subject self-reporting, and changes in vital sign).

  12 Months

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 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% 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
• Participant 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:
• Presence of corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR
• 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
• United States Department of Defense: collaborator
• Bascom Palmer Eye Institute: collaborator
• New York Presbyterian Hospital: collaborator

Study Sites (3)

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

New York Presbyterian Hospital

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Corneal Neovascularization

Interventions

Bevacizumab; Carboxymethylcellulose Sodium; Sodium Chloride

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Neovascularization, Pathologic; 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: Reza Dana, M.D., M. Sc, MPH
• Organization: Mass. Eye and Ear

Reza_Dana@meei.harvard.edu

6175734331

Study Officials

• Reza Dana, MD, MPH, MSc

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Cornea and Refractive Surgery Service

Study Record Dates

• First Submitted: November 22, 2013
• First Posted: November 27, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: August 10, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)