Venous UlcerPhase 4NCT01327937
A Post Marketing Study of Apligraf in Non-healing Wounds of Subjects With Venous Leg Ulcers
A Phase 4 study testing Apligraf in people with Venous Ulcer, run by Organogenesis at 1 site in United States.
Trial summary
The overall study objective is to use microarray technology to identify and characterize the gene expression of multiple relevant genes in biopsies of non-healing venous ulcers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Ulcer
- What is being tested?
- Apligraf
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Dec 2013
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has at least 1 clinically non-infected full-thickness venous leg ulcer (VLU) at least 5 cm2 in size.
- Subject is at least 18 years of age or older.
- Subject must have read, understood and signed an institutional review board (IRB) approved Informed Consent Form.
- Subject must be able and willing to follow study procedures and instructions.
Who cannot join
- Subjects who require VAC® (Vacuum Assisted Closure™) therapy on or after Day 0 Study visit.
- Subject has arterial disease as determined by an Ankle Brachial Index (ABI) measurement of <0.65.
- Subject with any systemic or congenital condition like uncontrolled diabetes mellitus, positive HIV test, or any disorder(s) that may compromise wound healing.
- Subjects with carcinomas located at the target ulcer with biopsy confirmed active malignancy. (Subjects with other carcinoma locations would not be excluded from entry into the study.)
- Subjects who are currently receiving, or have received at any time within 30 days prior to Screening visit, non-inhaled corticosteroids except topical steroids not at the target ulcer (Inhaled steroid therapy is acceptable on study.), immunosuppressive agents, radiation therapy, hemodialysis, peritoneal dialysis or chemotherapy. (Anticipated use of the above agents or therapies would exclude subject from entry into the study.)
- Clinical vasculitis, severe rheumatoid arthritis, and other collagen vascular diseases.
Show all 17Show fewer
- Signs and symptoms of cellulitis or osteomyelitis at the target ulcer.
- Avascular target ulcer beds. (Ulcers of mixed etiology such as arterial disease with VLU will be excluded.)
- Target ulcer with exposed bone, tendon or fascia.
- Known hypersensitivity to bovine collagen or to the components of the Apligraf agarose shipping medium.
- Subject enrolled in any wound or investigational study (drug, biologic or device) for any disease within 30 days of the Screening visit.
- Subject previously treated with Apligraf, Dermagraft® or any other cell therapy at the target ulcer site within 30 days of the Screening visit.
- Subject with a history of alcohol or substance abuse within the previous year, which could interfere with study compliance such as inability to attend scheduled study visits.
- Subject who is a current smoker or has not ceased smoking 6 months prior to the Screening visit, or in the opinion of the Investigator, has a smoking history that may compromise wound healing.
- Subject who, in the opinion of the Investigator, for any reason other than those listed above, will not be able to complete the study per protocol.
- Target ulcer has not decreased in size by > 40% from Screening to Day 0.
- Confirmed gene expression overlap between the subject's cells (buccal swab) and the cells contained in Apligraf.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Randomized, Controlled, Single-Site Post Marketing Study to Identify & Characterize the Molecular Mechanisms of Apligraf in Non-healing Wounds of Subjects With Venous Leg Ulcers
The overall study objective is to use microarray technology to identify and characterize the gene expression of multiple relevant genes in biopsies of non-healing venous ulcers.
Read the detailed description
Subjects with a ≥5 cm2, non-infected target ulcer that has not reduced in area by ≥ 40% since the Screening visit will be randomized at Day 0 to either Apligraf or Control. After enrollment of 25 subjects, randomization will be discontinued and all remaining subjects will receive Apligraf.
Once the target ulcer is assessed by the Investigator as healed at a study visit, the subject's participation in the study is completed (eg, assessed as healed at Week 3, subject would not be required to complete any subsequent study visits).
Apligraf Group (Day 0 to Week 4) Prior to all applications, Apligraf will be fenestrated (perforated) in a standardized manner using a #11 blade with 6 fenestrations per 44 cm2.
For those subjects randomized to the Apligraf group, after Apligraf application, the dressing regimen will include a foam dressing (eg. Mepilex) and a 4 layered compression bandage system (eg. Profore) which will be changed weekly by the Investigator.
After the initial Apligraf application at study Day 0, Apligraf may be applied weekly thereafter for an additional 4 weeks at study Weeks 1, 2, 3, and 4, if, upon visual inspection, adherent Apligraf wound coverage is < 100%.
At Week 4, the area of the target ulcer will be compared to the area of the target ulcer at Day 0 to determine if the target ulcer is PTH or NPTH.
Apligraf subjects that do not achieve CWC by Week 5 will enter the Follow-Up Phase at that time.
Control Group (Day 0 to Week 4 [PTH] or Day 0 to Week 8 [NPTH] Beginning at Day 0, subjects randomized to the Control group will receive the standard dressing regimen which includes a foam dressing (e.g. Mepilex®) and a four layered compression bandage system (e.g. Profore™) which will be changed weekly by the Investigator.
At study Week 4, the size of the ulcer will be compared to the size at study Day 0 to determine if the ulcer is demonstrating "Predicted to Heal" (PTH), defined as >40% reduction in ulcer surface area compared with study Day 0, or "Not Predicted to Heal (NPTH), defined as <40% reduction in ulcer surface area compared with study Day 0.
Control PTH subjects that do not achieve CWC by Week 4 will continue to receive Control treatment and will enter the Follow-Up Phase at Week 5.
Control NPTH subjects will receive Apligraf beginning at Week 4. Prior to all applications, Apligraf will be fenestrated (perforated) in a standardized manner using a #11 blade with 6 fenestrations per 44 cm2. After the initial Apligraf application at Week 4, Apligraf may be applied weekly thereafter for an additional 4 weeks at study Weeks 5, 6, 7, and 8 if upon visual inspection, adherent Apligraf wound coverage is < 100%. After Apligraf application, the standard dressing regimen will be applied over the target ulcer. The dressing will be changed weekly by the Investigator. At Week 8, the area of the target ulcer will be compared to the area of the target ulcer at Week 4 to determine if the target ulcer is PTH or NPTH.
Control NPTH subjects that do not achieve CWC by Week 9 will enter the Follow-up Phase at that time.
- Conditions
- Venous Ulcer
- Being tested
- Apligraf, Standard of Care Dressing Group
- Medical subject headings
- Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApligrafDevice
Apligraf group - Applied at Day 0, Weeks 1-4 (maximum of 5 applications) Also cross-over at Week 4 for Control NPTH group - Apligraf applied at Week 4, Weeks 5-8 (maximum of 5 applications)
Standard of Care Dressing GroupOther
Standard dressing regimen - Foam dressing (eg, Mepilex) and 4 layered compression system (eg, Profore)
| Study group | Role | What they receive |
|---|---|---|
| Apligraf Group | Active comparator | Apligraf group - Applied at Day 0, Weeks 1-4 (maximum of 5 applications) Also cross-over at Week 4 for Control NPTH group - Apligraf applied at Week 4, Weeks 5-8 (maximum of 5 applications) Receives: Device: Apligraf |
| Standard of Care Dressing Group | Placebo comparator | Standard of care dressing regimen - Foam dressing (eg, Mepilex) and 4 layered compression system (eg, Profore) Receives: Other: Standard of Care Dressing Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine changes in gene expression in subjects receiving Apligraf (includes Apligraf & Control NPTH) compared to 1 week post treatment
Not Predicted to Heal (NPTH) defined as <40% reduction in ulcer surface area from Day 0 to Week 4
Measured: Apligraf group - Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
Secondary outcomes (2)
Determine changes in gene expression in subjects receiving Apligraf (includes Apligraf & Control NPTH)compared to subjects not receiving Apligraf at time of initial treatment and at 1 week post treatment
NPTH defined as above
Measured: Apligraf group-Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
Determine differences in gene expression in following groups (see description section)
- Apligraf (APG) subjects Predicted to Heal (PTH) compared to Apligraf subjects Not Predicted to Heal (NPTH)
- APG subjects PTH compared to Control subjects PTH
- APG subjects NPTH compared to Control subjects NPTH
- Control subjects PTH compared to Control subjects NPTH
- All subjects (Apligraf and Control) PTH compared to all subjects NPTH
Also evaluate validity of surrogate endpoint (ulcer decrease of>/= 40% from Day 0 to Week 4) for complete wound closure (CWC*) by Week 24
- CWC defined as 100% epithelialization with absence of drainage
Measured: Apligraf group-Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2011 (estimated)
- Study startMar 2011
- Primary completionNov 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Venous UlcerStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organogenesis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Evangelos Badiavas, MD, PhD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01327937
- Sponsor's protocol ID
- 09-MOA-002-AG
- Status last verified
- Sep 2015
- First submitted
- 31 Mar 2011
- Last updated
- 24 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Stone RC, Stojadinovic O, Sawaya AP, Glinos GD, Lindley LE, Pastar I, Badiavas E, Tomic-Canic M. A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFbeta to stimulate remodeling of fibrotic venous leg ulcers. Wound Repair Regen. 2020 Mar;28(2):164-176. doi: 10.1111/wrr.12778. Epub 2019 Dec 4.
PubMed 31674093Stone RC, Stojadinovic O, Rosa AM, Ramirez HA, Badiavas E, Blumenberg M, Tomic-Canic M. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci Transl Med. 2017 Jan 4;9(371):eaaf8611. doi: 10.1126/scitranslmed.aaf8611.
PubMed 28053158
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Controlled, Single-Site Post Marketing Study to Identify & Characterize the Molecular Mechanisms of Apligraf in Non-healing Wounds of Subjects With Venous Leg Ulcers
- ClinicalTrials.gov ID
- NCT01327937
- Acronym / sponsor ID
- 09-MOA-002-AG
- Conditions
- Venous Ulcer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- OrganogenesisIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 4 Apr 2011 (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.
The overall study objective is to use microarray technology to identify and characterize the gene expression of multiple relevant genes in biopsies of non-healing venous ulcers.
Detailed description
Subjects with a ≥5 cm2, non-infected target ulcer that has not reduced in area by ≥ 40% since the Screening visit will be randomized at Day 0 to either Apligraf or Control. After enrollment of 25 subjects, randomization will be discontinued and all remaining subjects will receive Apligraf.
Once the target ulcer is assessed by the Investigator as healed at a study visit, the subject's participation in the study is completed (eg, assessed as healed at Week 3, subject would not be required to complete any subsequent study visits).
Apligraf Group (Day 0 to Week 4) Prior to all applications, Apligraf will be fenestrated (perforated) in a standardized manner using a #11 blade with 6 fenestrations per 44 cm2.
For those subjects randomized to the Apligraf group, after Apligraf application, the dressing regimen will include a foam dressing (eg. Mepilex) and a 4 layered compression bandage system (eg. Profore) which will be changed weekly by the Investigator.
After the initial Apligraf application at study Day 0, Apligraf may be applied weekly thereafter for an additional 4 weeks at study Weeks 1, 2, 3, and 4, if, upon visual inspection, adherent Apligraf wound coverage is < 100%.
At Week 4, the area of the target ulcer will be compared to the area of the target ulcer at Day 0 to determine if the target ulcer is PTH or NPTH.
Apligraf subjects that do not achieve CWC by Week 5 will enter the Follow-Up Phase at that time.
Control Group (Day 0 to Week 4 [PTH] or Day 0 to Week 8 [NPTH] Beginning at Day 0, subjects randomized to the Control group will receive the standard dressing regimen which includes a foam dressing (e.g. Mepilex®) and a four layered compression bandage system (e.g. Profore™) which will be changed weekly by the Investigator.
At study Week 4, the size of the ulcer will be compared to the size at study Day 0 to determine if the ulcer is demonstrating "Predicted to Heal" (PTH), defined as >40% reduction in ulcer surface area compared with study Day 0, or "Not Predicted to Heal (NPTH), defined as <40% reduction in ulcer surface area compared with study Day 0.
Control PTH subjects that do not achieve CWC by Week 4 will continue to receive Control treatment and will enter the Follow-Up Phase at Week 5.
Control NPTH subjects will receive Apligraf beginning at Week 4. Prior to all applications, Apligraf will be fenestrated (perforated) in a standardized manner using a #11 blade with 6 fenestrations per 44 cm2. After the initial Apligraf application at Week 4, Apligraf may be applied weekly thereafter for an additional 4 weeks at study Weeks 5, 6, 7, and 8 if upon visual inspection, adherent Apligraf wound coverage is < 100%. After Apligraf application, the standard dressing regimen will be applied over the target ulcer. The dressing will be changed weekly by the Investigator. At Week 8, the area of the target ulcer will be compared to the area of the target ulcer at Week 4 to determine if the target ulcer is PTH or NPTH.
Control NPTH subjects that do not achieve CWC by Week 9 will enter the Follow-up Phase at that time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apligraf Group | Active comparator | Device: ApligrafApligraf group - Applied at Day 0, Weeks 1-4 (maximum of 5 applications) Also cross-over at Week 4 for Control NPTH group - Apligraf applied at Week 4, Weeks 5-8 (maximum of 5 applications) |
| Standard of Care Dressing Group | Placebo comparator | Other: Standard of Care Dressing GroupStandard of care dressing regimen - Foam dressing (eg, Mepilex) and 4 layered compression system (eg, Profore) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subject has at least 1 clinically non-infected full-thickness venous leg ulcer (VLU) at least 5 cm2 in size.
- Subject is at least 18 years of age or older.
- Subject must have read, understood and signed an institutional review board (IRB) approved Informed Consent Form.
- Subject must be able and willing to follow study procedures and instructions.
Key exclusion criteria (17 listed)
- Subjects who require VAC® (Vacuum Assisted Closure™) therapy on or after Day 0 Study visit.
- Subject has arterial disease as determined by an Ankle Brachial Index (ABI) measurement of <0.65.
- Subject with any systemic or congenital condition like uncontrolled diabetes mellitus, positive HIV test, or any disorder(s) that may compromise wound healing.
- Subjects with carcinomas located at the target ulcer with biopsy confirmed active malignancy. (Subjects with other carcinoma locations would not be excluded from entry into the study.)
- Subjects who are currently receiving, or have received at any time within 30 days prior to Screening visit, non-inhaled corticosteroids except topical steroids not at the target ulcer (Inhaled steroid therapy is acceptable on study.), immunosuppressive agents, radiation therapy, hemodialysis, peritoneal dialysis or chemotherapy. (Anticipated use of the above agents or therapies would exclude subject from entry into the study.)
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 |
|---|---|---|
| ApligrafApligraf group - Applied at Day 0, Weeks 1-4 (maximum of 5 applications) Also cross-over at Week 4 for Control NPTH group - Apligraf applied at Week 4, Weeks 5-8 (maximum of 5 applications) | Device | Apligraf Group |
| Standard of Care Dressing GroupStandard dressing regimen - Foam dressing (eg, Mepilex) and 4 layered compression system (eg, Profore) | Other | Standard of Care Dressing Group |
Primary outcome
Determine changes in gene expression in subjects receiving Apligraf (includes Apligraf & Control NPTH) compared to 1 week post treatment
Time frame: Apligraf group - Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
Not Predicted to Heal (NPTH) defined as <40% reduction in ulcer surface area from Day 0 to Week 4
2 secondary outcomes
Determine changes in gene expression in subjects receiving Apligraf (includes Apligraf & Control NPTH)compared to subjects not receiving Apligraf at time of initial treatment and at 1 week post treatment
Time frame: Apligraf group-Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
Determine differences in gene expression in following groups (see description section)
Time frame: Apligraf group-Day 0 & Week 1; Control NPTH group-Weeks 4 & 5
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 24 Sep 2015.
- Derived from this study: PubMed 31674093Stone RC, Stojadinovic O, Sawaya AP, Glinos GD, Lindley LE, Pastar I, Badiavas E, Tomic-Canic M. A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFbeta to stimulate remodeling of fibrotic venous leg ulcers. Wound Repair Regen. 2020 Mar;28(2):164-176. doi: 10.1111/wrr.12778. Epub 2019 Dec 4.
- Derived from this study: PubMed 28053158Stone RC, Stojadinovic O, Rosa AM, Ramirez HA, Badiavas E, Blumenberg M, Tomic-Canic M. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci Transl Med. 2017 Jan 4;9(371):eaaf8611. doi: 10.1126/scitranslmed.aaf8611.
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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.
Evangelos Badiavas, MD, PhD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Apligraf in people with Venous Ulcer, run by Organogenesis 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 4 inclusion and 17 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 24 Sep 2015. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Determine changes in gene expression in subjects receiving Apligraf (includes Apligraf & Control NPTH) compared to 1 week post treatment (time frame: Apligraf group - Day 0 & Week 1; Control NPTH group-Weeks 4 & 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01327937, which also lists 2 linked publications.
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 24 Sep 2015; AzTrials last refreshed its copy on 7 Nov 2026.