- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000431
Preliminary Testing of New Treatment for Chronic Leg Wounds
Phase I Trial to Evaluate the Safety of Platelet Derived Growth Factor B (PDGF-B) and a Limb Compression Bandage in Venous Leg Ulcers
Study Overview
Detailed Description
Most chronic wounds of the leg fail to heal in a reasonable period of time. In fact, despite considerable advances in elucidating the molecular basis of wound repair, attempts to develop new therapies have been disappointing. In general, therapies based on recently elucidated mechanisms of wound repair have had minimal effect on the overall number of individuals with a treated healed chronic wound. The long-term goal of this study is to evaluate a new approach for healing a chronic wound. Current methods of applying cytokines as a topical protein to treat chronic wounds result in an inadequate response. PDGF-B, a growth factor associated with wound healing, might dramatically enhance wound healing when produced in large quantities in the wound bed via adenovirus-mediated gene overexpression by the cells of the wound bed.
This study consists of two trials. The goal of Trial A, a dose-escalation trial, is to determine the maximum tolerated dose (MTD) of PDGF-B/Ad5, an adenovirus vector designed to overexpress PDGF-B, with respect to local and systemic toxicity and biologic feasibility. The primary objective is to evaluate the acute safety, both local and systemic, of an intra-ulcer injection of PDGF-B/Ad5, thereby determining the recommended dose. Upon evaluating patients, they will be treated with a single intra-ulcer injection of PDGF-B/Ad5 in the wound. Patients will receive only one dose, which will be administered during a 72-hour inpatient stay in a research unit at the Hospital of the University of Pennsylvania.
This study will use a standard three-six dose-escalation scheme. The MTD is defined as the highest dose for which fewer than two of six subjects experience a severe adverse reaction. Each patient will be closely monitored for clinical adverse reactions resulting from treatment with PDGF-B/Ad5. Toxicity will be graded according to the National Cancer Institute's Common Toxicity Criteria Scale.
The primary objective of Trial B is to evaluate the safety and biologic feasibility of the MTD of PDGF-B/Ad5 reported in Trial A in a standard 24-week trial for treatment of a venous leg ulcer. For this study, 15 consecutive patients will be treated using the MTD. All patients will receive a single intra-ulcer injection of PDGF-B/Ad5 and a limb compression bandage to be changed weekly.Study participants will be followed for 24 weeks, which is the length of most FDA-approved venous leg ulcer trials.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient must have a venous leg ulcer.
- Patient must have failed at least 6 weeks of limb compression.
- Wound must be free of necrotic debris.
- Wound must be greater than 5 cm2 and less than 20 cm2.
- Wound must be more than 6 months old.
- Affected limb must have an ankle-brachial index (ABI) > 0.85.
- Patient must be more than 18 years old.
Exclusion Criteria:
- Any active cancer or cancer in remission for less than 10 years.
- Patients with life expectancy of less than 6 months.
- Liver function tests (Alanine Transaminase(ALT) Aspartate Amino Transfer (AST) Alkaline Phosphatase (ALK PHOS) and bilirubin) greater than 1.5x upper limit of normal for the reference lab.
- Patients with intercurrent organ damage or medical problems.
- Pregnant or lactating females.
- Any requirement for systemic corticosteroids or immunosuppressives, or history of corticosteroid or immunosuppressive use in the 4 weeks previous to study entry.
- Seropositive for hepatitis B surface antigen or hepatitis C antibody.
- Any concurrent medical illness that may be exacerbated by PDGF-B/Ad5 administration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Upon evaluation, participant will be treated with a single intra-ulcer injection of PDGF-B/Ad5 in the wound.
Patients will receive only one dose, which will be administered during a 72-hour inpatient stay in a research unit at the Hospital of the University of Pennsylvania.
This study will use a standard three-six dose-escalation scheme.
|
This is a dose finding study to evaluate the safety of a single injection of PDGF dna in an adenoviral vector.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety of treatment
Time Frame: Wtihin 28 days of administration
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Wtihin 28 days of administration
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proof of concept
Time Frame: Within 28 days of administration
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Within 28 days of administration
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David J. Margolis, MD, University of Pennsylvania
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- N01 AR92238
- N01AR092238-000 (U.S. NIH Grant/Contract)
- NIAMS-044
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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