WoundPhase 1/2NCT00664352
Juvidex (Mannose-6-Phosphate) in Accelerating the Healing of Split Thickness Skin Graft Donor Sites
A Phase 1/2 study testing Mannose-6-Phosphate (Juvidex) and Mannose-6-Phophate (Juvidex) in people with Wound, run by Renovo at 1 site in United Kingdom.
Trial summary
The objective of this study is to compare the efficacy of two concentrations of Juvidex with placebo on the healing of split thickness skin graft donor sites Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Wound
- What is being tested?
- Mannose-6-Phosphate (Juvidex) and Mannose-6-Phophate (Juvidex)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 195 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2008to Nov 2008
- Phase
- Phase 1/2
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects aged 18-85 years who have given written informed consent.
- A body mass index between 18-35 calculated using Quetelets index-weight (kg)/height² (m).
- Subjects with, in the opinion of the Investigator, clinically acceptable results for the laboratory tests and ECG as specified in the trial protocol (see Protocol Section 6.4.2). All laboratory tests must be performed within 28 days of the first trial dose administration.
- Female patients of child bearing potential who are using a highly effective method(s) of contraception and agree to do so from at least the screening visit until one month after administration of the final study dose. For the purposes of the protocol, highly effective method(s) of contraception will be defined as consistently and correctly used implants, injectables, combined oral contraceptives, sexual abstinence or a vasectomised partner
Who cannot join
- Subjects who on direct questioning and physical examination have history or evidence of hypertrophic or keloid scarring.
- Subjects with tattoos, birthmarks, moles or previous scars within 3cm of the area to be investigated during the trial.
- Afro-Caribbean subjects are excluded because of the increased susceptibility to hypertrophic and keloid scarring.
- Subjects who have had surgery in the area to be investigated within one year of the first dosing day.
- Subjects with a skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
- Subjects with any clinically significant medical condition or history of any condition that would impair wound healing including :
Show all 27Show fewer
- Subjects with renal impairment (creatinine clearance (CLcr) of 80/ml/min or less)
- Significant hepatic impairment (LFTs >3 times upper limit of normal).
- Congestive heart failure with a classification of >2 according to the NYHA Classification (see appendix 5).
- A history of myocardial infarction, ischaemic heart disease (or presenting with symptoms or signs compatible with ischaemic heart disease), coronary vasospasm or peripheral vascular disease.
- Subjects, with significant cerebrovascular disease including a history of stroke, transient ischaemic attacks or haemorrhage.
- Malignancy (unless treated and disease-free for 5 years).
- Autoimmune disease (including active rheumatoid arthritis), immunosuppression (oral corticosteroids) or chemotherapy within the last 12 months.
- Uncontrolled hypertension SBP > 180 mmHg, DBP > 95mmHg.
- Diabetes (except diet controlled)
- Significant respiratory disease.
- Subjects with a history of clinically relevant allergy, hypersensitivity, angioedema, or anaphylaxis.
- Subjects with a progressive neurological condition including Parkinson's disease, Alzheimer's disease and uncontrolled epilepsy.
- Subjects with a known history of chronic viral infection (Hepatitis, HIV) or ongoing active infection.
- Subjects with bleeding disorders including haemophilia, purpura or thrombocytopenia or receiving anticoagulants (e.g. warfarin, coumadin).
- Subjects who have taken any investigational product in the twelve months prior to first trial dose administration.
- Subjects undergoing investigations or changes in management for an existing medical condition.
- Subjects with a history of substance abuse or dependency ( a history of recreational use of cannabis is acceptable assuming a negative urine test for cannabis at screen. Subjects who have had a history of alcohol abuse but have been dependency free for 12 months will still be eligible).
- Subjects with any condition or serious illness which, in the opinion of the Investigator, would interfere with participation in the study.
- Subjects with an ongoing psychiatric condition requiring treatment or psychosis (including depression with psychosis, bipolar disease and schizophrenia).
- Female subjects who are breast feeding, or intending to become pregnant or breast feed during the study period (subjects must be using adequate contraception and have a negative pregnancy test at screening - see Inclusion).
- Female subjects who have had any change in their oral contraceptive medication (if applicable) in the 2 months prior to screening, or anticipate any change during study participation.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
09Clinical Trials Unit, Renovo Limited
Manchester, M13 9XX
About this study
Official title: A Double Blind, Placebo Controlled Trial to Investigate the Efficacy and Safety of Two Concentrations of Juvidex (Mannose-6-Phosphate) in Accelerating the Healing of Split Thickness Skin Graft Donor Sites Using Different Dosing Regimes
The objective of this study is to compare the efficacy of two concentrations of Juvidex with placebo on the healing of split thickness skin graft donor sites
Read the detailed description
Split thickness skin grafting is the transplantation of a patient's own cutaneous tissue harvested from an area of normal skin, to replace an area of skin loss or injury. The split thickness skin graft (SSG) is one of the most commonly performed operations in plastic and reconstructive surgery1. Indications for split skin grafting include: reconstruction after the surgical removal of cutaneous malignancies, to replace tissue lost in full-thickness burns and to cover chronic non-healing cutaneous ulcers. As with all grafting procedures, a donor site wound is created, and, in the case of SSGs, the wound is a partial-thickness wound that heals by re-epithelialisation. Often, the graft donor site is the slowest to heal, and it is the source of most of the postoperative discomfort. In patients who have sustained major burns affecting large percentages of their cutaneous surface area, early closure of burn wounds with autologous skin grafts can be limited by the lack of adequate donor sites. These donor sites may need to be re-harvested to provide further skin cover; however a delay of 2 to 3 weeks is often required to allow these sites to heal prior to re-harvesting.
A treatment to accelerate the healing of SSG donor sites produced after harvest would address an area of high medical need, not only by providing an area available for re-harvest, but also by reducing the potential associated morbidities to the patient including pain and infection. This could also reduce length of hospital stay with associated reduced healthcare costs.
Transforming growth factor betas (TGF-beta), are a naturally occurring protein which plays a central role in the wound healing response. Juvidex is being developed by Renovo as a therapeutic agent administered to accelerate the healing of acute wounds. The proposed mechanism of action is antagonistic and involves inhibiting the activation of TGF-beta 1 and TGF beta 2.
Using healthy volunteers is an ideal way of studying the healing process on split thickness skin graft donor sites since the donor sites can be created so that they are exactly anatomically matched. These matched pairs can then be used to compare drug against placebo.
The trial is being undertaken to assess the effects of intradermally injected and topically applied Juvidex on the healing of small skin graft donor sites in volunteer subjects. The trial will also compare the effects of a placebo treatment with standard care alone in the healing of the donor sites. This will enable any placebo effect to be accurately measured and allow an accurate assessment of actual drug effect.
- Conditions
- Wound
- Being tested
- Mannose-6-Phosphate (Juvidex), Mannose-6-Phophate (Juvidex), Placebo
- Keywords
- Double blind, Placebo controlled, wound healing
- Medical subject headings
- Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mannose-6-Phosphate (Juvidex)Drug
- 100µL of 300mM (8.46 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
- 100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
Mannose-6-Phosphate (Juvidex)Drug
- 100µL of 600mM(16.93 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
- 100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
Mannose-6-Phosphate (Juvidex)Drug
- 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
- 300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
Mannose-6-Phophate (Juvidex)Drug
- 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
- 300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
PlaceboDrug
- 100µL of placebo will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
- Standard Care (moist wound healing dressings alone) will be applied to the other 3cm2 donor site.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Mannose-6-Phosphate (Juvidex) |
| 2 | Experimental | Not described Receives: Drug: Mannose-6-Phosphate (Juvidex) |
| 3 | Experimental | Not described Receives: Drug: Mannose-6-Phosphate (Juvidex) |
| 4 | Experimental | Not described Receives: Drug: Mannose-6-Phophate (Juvidex) |
| 5 | Other | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time to complete wound closure as assessed by the investigating physician
Measured: Measured up to Day 28
Secondary outcomes (1)
Local wound tolerability
Measured: Up to Day 28 after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study startFeb 2008
- Primary completionOct 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for WoundStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 195 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Renovo
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Jim Bush, MBChB. MRCS, Principal investigator, General Medical Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00664352
- Sponsor's protocol ID
- RN1004-0082
- Status last verified
- Jan 2009
- First submitted
- 21 Apr 2008
- Last updated
- 6 Jan 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Placebo Controlled Trial to Investigate the Efficacy and Safety of Two Concentrations of Juvidex (Mannose-6-Phosphate) in Accelerating the Healing of Split Thickness Skin Graft Donor Sites Using Different Dosing Regimes
- ClinicalTrials.gov ID
- NCT00664352
- Acronym / sponsor ID
- RN1004-0082
- Conditions
- Wound
- Keywords
- Double blind, Placebo controlled, wound healing
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 195 participants (estimated)
- Lead sponsor
- RenovoIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Oct 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 22 Apr 2008 (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 objective of this study is to compare the efficacy of two concentrations of Juvidex with placebo on the healing of split thickness skin graft donor sites
Detailed description
Split thickness skin grafting is the transplantation of a patient's own cutaneous tissue harvested from an area of normal skin, to replace an area of skin loss or injury. The split thickness skin graft (SSG) is one of the most commonly performed operations in plastic and reconstructive surgery1. Indications for split skin grafting include: reconstruction after the surgical removal of cutaneous malignancies, to replace tissue lost in full-thickness burns and to cover chronic non-healing cutaneous ulcers. As with all grafting procedures, a donor site wound is created, and, in the case of SSGs, the wound is a partial-thickness wound that heals by re-epithelialisation. Often, the graft donor site is the slowest to heal, and it is the source of most of the postoperative discomfort. In patients who have sustained major burns affecting large percentages of their cutaneous surface area, early closure of burn wounds with autologous skin grafts can be limited by the lack of adequate donor sites. These donor sites may need to be re-harvested to provide further skin cover; however a delay of 2 to 3 weeks is often required to allow these sites to heal prior to re-harvesting.
A treatment to accelerate the healing of SSG donor sites produced after harvest would address an area of high medical need, not only by providing an area available for re-harvest, but also by reducing the potential associated morbidities to the patient including pain and infection. This could also reduce length of hospital stay with associated reduced healthcare costs.
Transforming growth factor betas (TGF-beta), are a naturally occurring protein which plays a central role in the wound healing response. Juvidex is being developed by Renovo as a therapeutic agent administered to accelerate the healing of acute wounds. The proposed mechanism of action is antagonistic and involves inhibiting the activation of TGF-beta 1 and TGF beta 2.
Using healthy volunteers is an ideal way of studying the healing process on split thickness skin graft donor sites since the donor sites can be created so that they are exactly anatomically matched. These matched pairs can then be used to compare drug against placebo.
The trial is being undertaken to assess the effects of intradermally injected and topically applied Juvidex on the healing of small skin graft donor sites in volunteer subjects. The trial will also compare the effects of a placebo treatment with standard care alone in the healing of the donor sites. This will enable any placebo effect to be accurately measured and allow an accurate assessment of actual drug effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Mannose-6-Phosphate (Juvidex) |
| 2 | Experimental | Drug: Mannose-6-Phosphate (Juvidex) |
| 3 | Experimental | Drug: Mannose-6-Phosphate (Juvidex) |
| 4 | Experimental | Drug: Mannose-6-Phophate (Juvidex) |
| 5 | Other | Drug: Placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects aged 18-85 years who have given written informed consent.
- A body mass index between 18-35 calculated using Quetelets index-weight (kg)/height² (m).
- Subjects with, in the opinion of the Investigator, clinically acceptable results for the laboratory tests and ECG as specified in the trial protocol (see Protocol Section 6.4.2). All laboratory tests must be performed within 28 days of the first trial dose administration.
- Female patients of child bearing potential who are using a highly effective method(s) of contraception and agree to do so from at least the screening visit until one month after administration of the final study dose. For the purposes of the protocol, highly effective method(s) of contraception will be defined as consistently and correctly used implants, injectables, combined oral contraceptives, sexual abstinence or a vasectomised partner
Key exclusion criteria (27 listed)
- Subjects who on direct questioning and physical examination have history or evidence of hypertrophic or keloid scarring.
- Subjects with tattoos, birthmarks, moles or previous scars within 3cm of the area to be investigated during the trial.
- Afro-Caribbean subjects are excluded because of the increased susceptibility to hypertrophic and keloid scarring.
- Subjects who have had surgery in the area to be investigated within one year of the first dosing day.
- Subjects with a skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
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 |
|---|---|---|
| Mannose-6-Phosphate (Juvidex)* 100µL of 300mM (8.46 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest. * 100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest. | Drug | 1 |
| Mannose-6-Phosphate (Juvidex)* 100µL of 600mM(16.93 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest. * 100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest. | Drug | 2 |
| Mannose-6-Phosphate (Juvidex)* 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest. * 300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest. | Drug | 3 |
| Mannose-6-Phophate (Juvidex)* 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest. * 300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest. | Drug | 4 |
| Placebo* 100µL of placebo will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest. * Standard Care (moist wound healing dressings alone) will be applied to the other 3cm2 donor site. | Drug | 5 |
Primary outcome
The time to complete wound closure as assessed by the investigating physician
Time frame: Measured up to Day 28
1 secondary outcome
Local wound tolerability
Time frame: Up to Day 28 after surgery
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 6 Jan 2009.
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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.
Jim Bush, MBChB. MRCS principal investigator
General Medical Council
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mannose-6-Phosphate (Juvidex) and Mannose-6-Phophate (Juvidex) in people with Wound, run by Renovo at 1 site in United Kingdom.
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 27 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 6 Jan 2009. 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 Kingdom. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The time to complete wound closure as assessed by the investigating physician (time frame: Measured up to Day 28). 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 6 Jan 2009.