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

This study has been terminated.
(slow recruitment)
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
RegeneRx Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00598871
First received: December 19, 2007
Last updated: December 5, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Diabetes
Drug: Thymosin Beta 4 (Tβ4)
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by RegeneRx Biopharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) After Treatment With Thymosin Beta 4 in the Target Eye of Diabetic Patients During Vitrectomy [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Number of Participants With Corneal Epithelial Wound Healing at Day 14 (End of Treatment) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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)


Enrollment: 12
Study Start Date: December 2007
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00598871

Locations
United States, California
United Medical Research Institute
Inglewood, California, United States, 90301
Doheny Eye Institute
Los Angeles, California, United States, 90033
United States, Florida
Magruder Eye Institue
Orlando, Florida, United States, 32803
United States, Georgia
Southeast Retina Center
Augusta, Georgia, United States, 30909
United States, North Carolina
Western Carolina Retinal Associates, PA
Asheville, North Carolina, United States, 28803
Sponsors and Collaborators
RegeneRx Biopharmaceuticals, Inc.
PPD
Investigators
Study Director: David R Crockford RegeneRx Biopharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: RegeneRx Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00598871     History of Changes
Other Study ID Numbers: RGN-DV-201
Study First Received: December 19, 2007
Results First Received: February 22, 2010
Last Updated: December 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by RegeneRx Biopharmaceuticals, Inc.:
Thymosin beta 4
Corneal wound healing
Vitrectomy
Diabetes

Additional relevant MeSH terms:
Ophthalmic Solutions
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014