Venous Stasis Ulcers
Conditions
Keywords
Venous Stasis Ulcers, venous insufficiency, leg ulcers, Thymosin Beta 4, Laminin-5
Brief summary
The purpose of this study is to evaluate the safety, tolerability and effectiveness of Thymosin Beta 4 administered topically in patients with Venous Stasis ulcers
Detailed description
The purpose of this double-blind, placebo-controlled, dose-response study is to evaluate the safety, tolerability and effectiveness of Thymosin Beta 4 (Tβ4), administered topically, in patients with Venous Stasis (VS) ulcers. VS ulcers develop on the ankle or lower leg in patients with chronic vascular disease. In these patients, blood flow in the lower extremities is impaired, leading to edema (swelling) and mild redness and scaling of the skin that gradually progress to ulceration. Tβ4 is a synthetically-produced copy of a naturally occurring 43 amino acid peptide that has wound healing and anti-inflammatory properties and can up-regulate the expression of laminin-5.
Interventions
DRUGThymosin Beta 4
There were 3 groups of patients with venous stasis (VS) ulcers. Each group included 18 patients receiving active drug and 6 receiving placebo. There were three concentrations of gel used for topical administration to the active groups: 0.01% weight/weight (w/w), 0.03% w/w, and 0.1% w/w thymosin beta 4 gel applied once daily for up to 84 days
DRUGPlacebo
There were 3 groups of patients with venous stasis (VS) ulcers. Each group included 18 patients receiving active drug and 6 receiving placebo. There was one concentration of placebo gel for topical administration to the placebo group. The concentration was 0.0% weight/weight (w/w) thymosin beta 4 gel applied once daily for up to 84 days
Sponsors
sigma-tau i.f.r. S.p.A.
RegeneRx Biopharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Informed Consent Form signed by the patient * Male or female, between 18 and 79 years of age * At least one venous leg ulceration stable for at least 6 weeks before enrollment * Surface area between 3 and 30 cm2
Exclusion criteria
* Have clinical evidence of active infection on the index ulcer * Use of any experimental drug, or participation in any clinical study, within the 60 days before enrollment * Use of systemic or topical steroidal therapy, immunotherapy, or cytotoxic chemotherapy within the 60 days before enrollment * History of adverse reaction to any ingredients of the study medication * Clinically significant neurological, cardiovascular, respiratory, hepatic, renal, metabolic and dermatologic disease other than venous ulcers * Current or former malignancy * Arterial disorder resulting in ulcerated ulcers * Diabetes mellitus * Pregnant or lactating (breastfeeding) women. A serum pregnancy test will be performed at screening for female patients of childbearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days | Up to 84 days | All Treatment-Emergent (TE) Serious Adverse Events (SAEs) and Adverse Events (AEs) by treatment with Tβ4 gel at the combined 3 doses in the safety population with Venous Stasis (VS) ulcers for up to 84 days. TEAE is defined as a side effect that begins or that worsens in severity after the application of at least one dose of Tβ4 gel on the venous stasis ulcer. A pre-existing condition is not considered an AE, but if it worsens during the study, then it may be considered an AE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Healing (Wound Closure Without Drainage) by Applying Tβ4 Gel Once Daily for up to 84 Days to Patients With Venous Stasis (VS) Ulcers | Up to 84 days | Wound healing effectiveness of Tβ4 gel applied once daily for up to 84 days to patients expressed as the number of patients whose wound had closed without drainage at the end of the study, Day 84 |
Countries
Italy, Poland
Participant flow
Recruitment details
Recruitment started in 2006 and ended in 2009 using 8 sites: University Medical Center Clinics
Pre-assignment details
Prior to randomization, patients need to meet specific inclusion and exclusion criteria. There was no wash-out or run-in periods
Participants by arm
| Arm | Count |
|---|---|
| Placebo 0.00% Thymosin Beta 4 (Tβ4), weight/weight (w/w) | 17 |
| Thymosin Beta 4 (Tβ4) at 3 Doses 0.01% Tβ4 weight by weight (w/w), 0.03% Tβ4 w/w, 0.1% Tβ4 w/w | 55 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Prohibited Medication | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 16 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 39 Participants | 48 Participants |
| Region of Enrollment Italy | 11 participants | 17 participants | 28 participants |
| Region of Enrollment Poland | 6 participants | 38 participants | 44 participants |
| Sex: Female, Male Female | 12 Participants | 28 Participants | 40 Participants |
| Sex: Female, Male Male | 5 Participants | 27 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 17 | 35 / 55 |
| serious Total, serious adverse events | 1 / 17 | 3 / 55 |
Outcome results
Primary
Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days
All Treatment-Emergent (TE) Serious Adverse Events (SAEs) and Adverse Events (AEs) by treatment with Tβ4 gel at the combined 3 doses in the safety population with Venous Stasis (VS) ulcers for up to 84 days. TEAE is defined as a side effect that begins or that worsens in severity after the application of at least one dose of Tβ4 gel on the venous stasis ulcer. A pre-existing condition is not considered an AE, but if it worsens during the study, then it may be considered an AE
Time frame: Up to 84 days
Population: Analysis per protocol, ITT, using LOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days | 24 SAEs and AEs |
| Thymosin Beta 4 (Tβ4) at 3 Doses | Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days | 104 SAEs and AEs |
Secondary
Wound Healing (Wound Closure Without Drainage) by Applying Tβ4 Gel Once Daily for up to 84 Days to Patients With Venous Stasis (VS) Ulcers
Wound healing effectiveness of Tβ4 gel applied once daily for up to 84 days to patients expressed as the number of patients whose wound had closed without drainage at the end of the study, Day 84
Time frame: Up to 84 days
Population: Analysis per protocol, Intent-to-treat (ITT), using Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Wound Healing (Wound Closure Without Drainage) by Applying Tβ4 Gel Once Daily for up to 84 Days to Patients With Venous Stasis (VS) Ulcers | 4 Participants |
| Thymosin Beta 4 (Tβ4) at 3 Doses | Wound Healing (Wound Closure Without Drainage) by Applying Tβ4 Gel Once Daily for up to 84 Days to Patients With Venous Stasis (VS) Ulcers | 12 Participants |