A Phase 2 interventional study of Thymosin Beta 4 (Tβ4) and Placebo in Diabetes, sponsored by ReGenTree, LLC. Terminated at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-07-08.
Sponsored by ReGenTree, LLC · Phase 2, Interventional, and Treatment
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.
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.
ReGenTree, LLC is the lead sponsor of 7 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria
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 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).
Also known as: Thymosin Beta 4 eye drops, Tβ4 eye drops, RGN-259
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).
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
Time frame: 14 days
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)
Time frame: 14 days
Recruitment started in January 2008 and ended February 2009 using 4 sites (Hospital Medical Centers). Only the first dose group was completed before suspending the trial due to low patient availability.The procedure of debridement was discontinued in most centers, thus making the availability of surgical subject extremely small.
| Milestone | Placebo | Active Drug |
|---|---|---|
| Started | 3 | 9 |
| Completed | 3 | 8 |
| Not completed | 0 | 1 |
| Withdrew: Adverse event | 0 | 1 |
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
| Participants | Placebo | Active Drug |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) After Treatment With Thymosin Beta 4 in the Target Eye of Diabetic Patients During Vitrectomy | 3 | 9 |
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)
| participants | Placebo | Active Drug |
|---|---|---|
| Number of Participants With Corneal Epithelial Wound Healing at Day 14 (End of Treatment) | 3 (29.2 to 100) | 9 (66.4 to 100) |
Collected over Adverse Events (AEs) were collected on a daily basis for the first 14 days and during follow-up at Day 28. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/3 (0%) | 3/3 (100%) |
| Active Drug | — | 0/9 (0%) | 9/9 (100%) |
| Event | Placebo | Active Drug |
|---|---|---|
| Anterior Chamber CellsEye disorders | 3/3 | 6/9 |
| Anterior Chamber FlareEye disorders | 3/3 | 6/9 |
| Conjunctival HaemorrhageEye disorders | 2/3 | 7/9 |
| Conjunctival oedemaEye disorders | 1/3 | 6/9 |
| Punctate KeratitisEye disorders | 2/3 | 5/9 |
| Corneal disorderEye disorders | 2/3 | 4/9 |
| Corneal oedemaEye disorders | 2/3 | 4/9 |
| Corneal StainingInvestigations | 2/3 | 4/9 |
| Eye PainEye disorders | 0/3 | 4/9 |
| Corneal ErosionEye disorders | 1/3 | 2/9 |
| Age, Continuous(years) | Placebo | Active Drug | Total |
|---|---|---|---|
| Mean | 43.3 ± 3.1 | 51.4 ± 15.0 | 49.4 ± 13.4 |
| Sex: Female, Male(Participants) | Placebo | Active Drug | Total |
|---|---|---|---|
| Female | 2 | 4 | 6 |
| Male | 1 | 5 | 6 |
This study is terminated, as verified in Nov 2012. You cannot join it, but the record below documents what was studied.
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