Varicose UlcerPhase 1NCT00000431
Preliminary Testing of New Treatment for Chronic Leg Wounds
A Phase 1 study testing PDGF-B/Ad5 in people with Varicose Ulcer, run by University of Pennsylvania at 1 site in United States.
Trial summary
Most chronic (long-lasting) wounds of the leg (also known as venous ulcers) fail to heal in a reasonable period of time. Although researchers have made great progress in understanding how the body repairs wounds, attempts to develop new treatments have been disappointing. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Varicose Ulcer
- What is being tested?
- PDGF-B/Ad5
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Mar 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase I Trial to Evaluate the Safety of Platelet Derived Growth Factor B (PDGF-B) and a Limb Compression Bandage in Venous Leg Ulcers
Most chronic (long-lasting) wounds of the leg (also known as venous ulcers) fail to heal in a reasonable period of time. Although researchers have made great progress in understanding how the body repairs wounds, attempts to develop new treatments have been disappointing. In general, treatments based on recent findings about the details of wound repair have not greatly reduced the number of people who have chronic wounds. The long-term goal of this study is to evaluate a new approach for healing a chronic wound. Current methods of directly applying substances that are involved in wound healing to a chronic wound do not cause enough healing. PDGF-B (platelet-derived growth factor B), a factor associated with wound healing, might dramatically enhance healing if a genetically engineered virus is injected into the wound that causes cells in the wound to produce PDGF-B in large quantities.
Read the 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.
- Conditions
- Varicose Ulcer
- Being tested
- PDGF-B/Ad5
- Keywords
- Venous leg ulcer, Wound healing, Somatic gene therapy, PDGF-B
- Medical subject headings
- Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDGF-B/Ad5Drug
This is a dose finding study to evaluate the safety of a single injection of PDGF dna in an adenoviral vector.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Drug: PDGF-B/Ad5 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of treatment
Measured: Wtihin 28 days of administration
Secondary outcomes (1)
Proof of concept
Measured: Within 28 days of administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2000 (estimated)
- Study startJan 2005
- Primary completionJul 2008
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Varicose UlcerStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Gene Vector Laboratory
- Responsible party
- Sponsor
- Investigators
- David J. Margolis, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000431
- Sponsor's protocol ID
- N01 AR92238
- Other IDs
- N01AR092238-000, NIAMS-044
- Status last verified
- Mar 2009
- First submitted
- 18 Jan 2000
- Last updated
- 13 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial to Evaluate the Safety of Platelet Derived Growth Factor B (PDGF-B) and a Limb Compression Bandage in Venous Leg Ulcers
- ClinicalTrials.gov ID
- NCT00000431
- Acronym / sponsor ID
- N01 AR92238
- Conditions
- Varicose Ulcer
- Keywords
- Venous leg ulcer, Wound healing, Somatic gene therapy, PDGF-B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Gene Vector Laboratory
- Study start
- Jan 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 19 Jan 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Most chronic (long-lasting) wounds of the leg (also known as venous ulcers) fail to heal in a reasonable period of time. Although researchers have made great progress in understanding how the body repairs wounds, attempts to develop new treatments have been disappointing. In general, treatments based on recent findings about the details of wound repair have not greatly reduced the number of people who have chronic wounds. The long-term goal of this study is to evaluate a new approach for healing a chronic wound. Current methods of directly applying substances that are involved in wound healing to a chronic wound do not cause enough healing. PDGF-B (platelet-derived growth factor B), a factor associated with wound healing, might dramatically enhance healing if a genetically engineered virus is injected into the wound that causes cells in the wound to produce PDGF-B in large quantities.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PDGF-B/Ad5Upon 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PDGF-B/Ad5This is a dose finding study to evaluate the safety of a single injection of PDGF dna in an adenoviral vector. | Drug | 1 |
Primary outcome
Safety of treatment
Time frame: Wtihin 28 days of administration
1 secondary outcome
Proof of concept
Time frame: Within 28 days of administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David J. Margolis, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PDGF-B/Ad5 in people with Varicose Ulcer, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of treatment (time frame: Wtihin 28 days of administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2013.