A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 for Treating Corneal Wounds

A Randomized, Double-Mask, Placebo-Controlled, Dose Response, Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 in the Treatment of Diabetic Patients' Corneal Wounds Resulting From Epithelial Debridement During Vitrectomy

As a consequence of damage to multiple organ systems throughout the course of their disease, diabetic patients suffer a number of chronic complications giving rise to increased morbidity, mortality, and health care costs specific to this population. Within the ophthalmic domain, diabetic retinopathy (DR) frequently induces serious visual impairment. Although DR can be addressed surgically, surgery remains a less than ideal intervention within this population with a well-characterized compromised ability to heal. The introduction of a therapeutic agent that could accelerate wound closure and decrease healing time, thereby reducing the risk and incidence of infection and corneal scarring in these susceptible patients, would represent a significant clinical and pharmacoeconomic advance in the treatment of this condition.

Study Overview

• Status: Terminated
• Conditions: Diabetes
• Intervention / Treatment: Other: Placebo; Drug: Thymosin Beta 4 (Tβ4)

Detailed Description

In individuals with certain clinical conditions, such as diabetes, corneal epithelial defects persist and do not necessarily respond to conventional treatment regimens because of delayed epithelial wound healing. While wound closure should occur following an injury to the corneal epithelium, a timely re-establishment of the epithelial barrier is of utmost importance.

The wound repair process is intricately linked to a complex inflammatory response that must be properly regulated to ensure healing and optimal visual outcome. Infiltration of inflammatory cells into injured corneal tissue is a hallmark of wound repair, and the association of polymorphonuclear (PMN) leukocyte infiltration with sterile corneal ulceration is well recognized. Retardation of epithelial recovery by persistent inflammation, release of enzymatic products from degranulating PMN, and stimulation of mononuclear leukocytes by cytokines all contribute to poor re-epithelialization.

It has been shown that diabetic corneas manifest reduced rates of epithelial healing after denudement. Yet, in the diabetic patient, not only is the rate of corneal epithelial healing of clinical concern, abnormalities inherent in the diabetic corneal epithelial cytoarchitecture can cause substantial impediments to normal stromal healing. Histologically, diabetic corneas typically demonstrate thickening of the epithelial basal membrane (BM), decreased number of hemidesmosomes, and decreased number of nerve fiber endings. Studies of BM changes in diabetic corneas have yielded information regarding poor adhesion of the epithelial BM to the stroma. During vitrectomy in diabetic patients, when the cornea epithelium is removed, it separates as an intact sheet and the entire thickened BM, characteristic of diabetes, adheres to the epithelium. In contrast, when normal epithelium is removed by scraping, the BM remains adherent to the stroma.

Because patients with diabetic retinopathy (DR) corneas have delayed wound healing, the expression of thymosin beta 4 (Tβ4) as a potent epithelial cell migration stimulator in DR corneas was investigated. Human DR corneas were analyzed and were found to express significantly less Tβ4 compared to normal corneas, suggesting that the use of Tβ4 may accelerate the wound-healing process in this model.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Inglewood, California, United States, 90301
      • United Medical Research Institute
    • Los Angeles, California, United States, 90033
      • Doheny Eye Institute
  • Florida
    • Orlando, Florida, United States, 32803
      • Magruder Eye Institue
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Type 1 or Type 2 diabetes mellitus.
• Patients who have an expected minimum 50% likelihood of requiring corneal epithelial debridement in the opinion of the Investigator Size of wound should be 8 mm.
• Signed written informed consent by patient or legal guardian.

Exclusion Criteria

• Have current or history of herpetic eye disease in the past 3 years.
• Display evidence of keratitis.
• Have Sjögren's syndrome.
• Have corneal scarring, opacity, or dystrophy.
• Have a history of malignancy.
• Have a history of HIV or AIDs
• Are pregnant or lactating females.
• Are females who can become pregnant.
• Have a known hypersensitivity to the study drug.
• May be regarded as unreliable for the study.
• Have previously participated in this study.
• Experience any complication during the vitrectomy procedure itself, which will exclude the patient from participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of eyedrops to the affected eye, identical to the active drug but with no thymosin beta 4 (0.00% thymosin beta 4, w/w), 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).	Other: Placebo; There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of 0.00% Tβ4(w/w) eyedrops to the affected eye, 2 drops four times a day (QID) (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).
Active Comparator: 1; There are 2 groups: active drug and placebo. The patients in the active comparator arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).	Drug: Thymosin Beta 4 (Tβ4); There are 2 groups: active drug and placebo. The patients in the active arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times daily (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).; Other Names: Thymosin Beta 4 eye drops; Tβ4 eye drops; RGN-259

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) After Treatment With Thymosin Beta 4 in the Target Eye of Diabetic Patients During Vitrectomy	Number of participants with Number of Treatment Emergent Adverse Events (TEAEs) in the Target Eye in diabetic patients who had undergone epithelial debridement during vitrectomy and treated with thymosin beta 4	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Corneal Epithelial Wound Healing at Day 14 (End of Treatment)	Number of diabetic patients who had undergone epithelial debridement during vitrectomy resulted in complete corneal wound closure of the affected eye at the end of treatment (Day 14)	14 days

Collaborators and Investigators

• Sponsor: ReGenTree, LLC
• Collaborators: PPD

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: January 11, 2008
• First Posted (Estimate): January 23, 2008

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Diabetes; Thymosin beta 4; Corneal wound healing; Vitrectomy
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: RGN-DV-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No