Diabetic Foot Ulcer of Neuropathic OriginPhase 3TRANS-NorthNCT01217476
The TRAfermin in Neuropathic Diabetic Foot Ulcer Study - Northern Europe The TRANS-North Study
A Phase 3 study testing Trafermin 0.01% spray in people with Diabetic Foot Ulcer of Neuropathic Origin, run by Olympus Biotech Corporation at 37 sites in 10 countries.
Trial summary
Trafermin is a recombinant human basic fibroblast growth factor (bFGF; original development code, KCB-1), which is manufactured by genetic engineering using Escherichia coli by Kaken Pharmaceutical Co., Ltd. (Tokyo, Japan). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer of Neuropathic Origin
- What is being tested?
- Trafermin 0.01% spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- 37 sitesin 10 countries
- Study dates
- Dec 2010to Mar 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients who fulfill all of the following criteria are eligible for randomization:
- All of the selection criteria and none of the exclusion criteria are met.
- Completed the 2-week placebo run-in period during which they were compliant to off-loading and to daily application of placebo spray, without major protocol violation. Compliance with the placebo run-in treatment regimen must be "excellent" or "acceptable".
- Glycosylated hemoglobin (HbA1c) below or equal 10% (from a blood sample taken during the placebo run-in period).
- Non-infected target foot DFU of confirmed neuropathic origin with:
- ABPI on the target leg (>0.9; below or equal 1.3) or if ABPI is >1.3 or is not assessable, TBPI on target foot above or equal 0.7, OR
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- ABPI on target leg (above or equal 0.7 - below or equal 0.9) or if ABPI is >1.3 or is not assessable, TBPI on target foot <0.7, AND a toe blood pressure >40 mmHg
- Target DFU appropriately debrided (<10% black and at least 50% of red/pink on a colorimetric scale)
- Target DFU of grade A1 or A2 on the University of Texas Wound Classification System or of Grade 1 or 2 of the Wagner classification.
- DFU surface area between above or equal 0.9 cm2 and below or equal 20 cm2 confirmed by the investigator's measurement, and its surface area not decreased by more than 40% compared to the selection value.
Who cannot join
- Patients who fulfill any of the following criteria are not eligible to be enrolled in the study:
- Active Charcot foot, or inactive Charcot foot, if the target DFU cannot be properly offloaded.
- Ulcers of non-neuropathic origin (e.g., rheumatoid, radiation-related, vasculitis-related ulcers).
- Presence of any foot ulcer (whether or not on the target foot) for which local or systemic antibiotic treatment is required.
- Evidence of skin cancer within or adjacent to the target ulcer.
- Any infected ulcers, defined as any problem such as (but not limited to) cellulitis, osteomyelitis, gangrene, or deep tissue infection requiring local or systemic antibiotic therapy.
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- Another wound on the same foot as the target DFU. (i.e. Patients with another wound on the same limb as the target DFU are eligible for the study provided the concomitant wound is not infected and is above the ankle of the target foot).
- Any known active malignancy that requires general, local, surgical or radiation therapy either ongoing or within the previous 6 months; or patients whose treatment has been suspended for compassionate reasons, or who are not considered as cured from any malignancy.
- Morbid obesity, defined as body mass index (BMI) above or equal 45 kg/m2.
- Clinically significant medical conditions, in the investigator's opinion, that could impair wound healing (e.g. hepatic impairment, immunocompromised patients).
- Severe renal failure, defined as requirement for hemodialysis or peritoneal dialysis.
- Females who are pregnant or breastfeeding, or who are of childbearing potential and not practicing a medically approved method of contraception.
- Concomitant treatment with high dose oral or parenteral corticosteroids, defined as a daily dose of at least 7.5 mg prednisone or equivalent.
- Participation in another clinical study within the previous 3 months.
- Current participation in another clinical study with any drug or device.
- History of drug or alcohol abuse within the previous year.
- Concurrent severe psychiatric disease (including severe depressive disorder).
- Known intolerance to the IMP or to any of its excipients.
- Known to be uncooperative or noncompliant.
- Outpatients who are unable to comply with the requirement for daily spray application at home (either application by a family member or by a visiting nurse).
- Any other condition which, in the opinion of the investigator, would render the patient unsuitable for the study.
Trial locations and contacts
37 sites in 10 countries.
37 sites in 10 countries
Poland10 sites
Study site
Kalisz, 62 800
Study site
Lodz, 90 302
Study site
Lodz, 94 238
Study site
Lublin, 20090
Study site
Poznan, 60111
Study site
Szczecin, 70 215
Study site
Warsaw, 00 132
Study site
Wroclaw, 50403
Study site
Wroclaw, 51124
Study site
Zielona Góra, 65 945
Germany6 sites
Study site
Bad Mergentheim, 97980
Study site
Bad Nauheim, 61231
Study site
Cologne, 50733
Study site
Münster, 48145
Study site
Oldenburg, 23758
Study site
Trier, 45292
Netherlands4 sites
Study site
Almelo, 7600
Study site
Amsterdam, 1105
Study site
Apeldoorn, 7334
Study site
Delft, 2625
Slovakia4 sites
Study site
Dunajská Streda, 929 01
Study site
L'ubochna, 034 91
Study site
Nové Zamky, 940 01
Study site
Vráble, 952 01
Belgium3 sites
Study site
Brussels, 1070
Study site
Liège, 4000
Study site
Rumst, 2840
Croatia3 sites
Study site
Crikvenica, 51 260
Study site
Pula, 52 100
Study site
Zagreb, 10 000
About this study
Official title: A Phase III, Double-Blind, Placebo Controlled, Parallel Group, International, Multicenter Study of 12 Weeks Treatment With Trafermin 0.01% Spray in Patients With Diabetic Foot Ulcer of Neuropathic Origin
Trafermin is a recombinant human basic fibroblast growth factor (bFGF; original development code, KCB-1), which is manufactured by genetic engineering using Escherichia coli by Kaken Pharmaceutical Co., Ltd. (Tokyo, Japan). Trafermin 0.01% cutaneous spray product kit consisting of a glass bottle containing lyophilized trafermin, a glass bottle with solvent for solution and a spray part to fit the glass bottle after reconstitution of the final product.
We conduct a multinational, randomized, double-blind, placebo controlled, parallel-group, multicentre study consisting of a placebo run-in phase (2w), a treatment phase (max. 12w) and a follow-up phase (3mo+6mo). The primary objective of the study is to demonstrate a superior wound closure rate of diabetic foot ulcers (DFUs) of neuropathic origin after a maximum of 12 weeks topical daily application of trafermin 0.01% spray compared with placebo, in addition to best local care (off-loading, dressings). Approximately 210 patients will be randomized and it is planned that this study will be conducted at approximately 40 investigational sites in Europe.
- Being tested
- Trafermin 0.01% spray
- Keywords
- Diabetic foot, Neuropathic, Wound, Growth factor
- Medical subject headings
- Diabetic Foot, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trafermin 0.01% sprayDrug
For ulcers with a maximum diameter (longest axis) of less or equal to 6 cm, the daily dose of trafermin 0.01% spray is 5 puffs (30 microgram) sprayed onto the wound surface. If the maximum diameter (longest axis) of the ulcer is >6 cm, the ulcer should be sprayed in two parts, i.e. 5 puffs (30 microgram) sprayed onto each half of the wound surface
| Study group | Role | What they receive |
|---|---|---|
| Trafermin 0.01% spray | Active comparator | Not described Receives: Drug: Trafermin 0.01% spray |
| Matching placebo spray | Placebo comparator | Not described Receives: Drug: Trafermin 0.01% spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wound Closure Rate of Diabetic Foot Ulcers (DFUs) of Neuropathic Origin After a Maximum of 12 Weeks Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition to Best Local Cares
wound closure is defined as 100% reepithelialization of the target DFU, without exudates.
Measured: 12 weeks
Secondary outcomes (1)
Relative Wound Area Regression of 40% or More at 6 Week
The incidence of wound area regression of at least 40% at week 6 was considered as an important exploratory secondary efficacy variable. The wound area regression was calculated as percentage change from inclusion at week 6 using centralized wound area data.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2010 (estimated)
- Study startDec 2010
- Primary completionMay 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic Foot Ulcer of Neuropathic OriginStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Olympus Biotech Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jean-Charles Kerihuel, MD, Study director, VERTICALLuc Téot, MD, Study chair, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01217476
- Sponsor's protocol ID
- TFM-CL3-002
- Other IDs
- 2010-021015-16
- Acronym
- TRANS-North
- Status last verified
- Aug 2014
- First submitted
- 7 Oct 2010
- Last updated
- 5 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Double-Blind, Placebo Controlled, Parallel Group, International, Multicenter Study of 12 Weeks Treatment With Trafermin 0.01% Spray in Patients With Diabetic Foot Ulcer of Neuropathic Origin
- ClinicalTrials.gov ID
- NCT01217476
- Acronym / sponsor ID
- TRANS-North / TFM-CL3-002
- Keywords
- Diabetic foot, Neuropathic, Wound, Growth factor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Olympus Biotech CorporationIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- May 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 8 Oct 2010 (estimated)
- Results
- Posted 5 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Trafermin is a recombinant human basic fibroblast growth factor (bFGF; original development code, KCB-1), which is manufactured by genetic engineering using Escherichia coli by Kaken Pharmaceutical Co., Ltd. (Tokyo, Japan). Trafermin 0.01% cutaneous spray product kit consisting of a glass bottle containing lyophilized trafermin, a glass bottle with solvent for solution and a spray part to fit the glass bottle after reconstitution of the final product.
We conduct a multinational, randomized, double-blind, placebo controlled, parallel-group, multicentre study consisting of a placebo run-in phase (2w), a treatment phase (max. 12w) and a follow-up phase (3mo+6mo). The primary objective of the study is to demonstrate a superior wound closure rate of diabetic foot ulcers (DFUs) of neuropathic origin after a maximum of 12 weeks topical daily application of trafermin 0.01% spray compared with placebo, in addition to best local care (off-loading, dressings). Approximately 210 patients will be randomized and it is planned that this study will be conducted at approximately 40 investigational sites in Europe.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trafermin 0.01% spray | Active comparator | Drug: Trafermin 0.01% spray |
| Matching placebo spray | Placebo comparator | Drug: Trafermin 0.01% spray |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- All of the selection criteria and none of the exclusion criteria are met.
- Completed the 2-week placebo run-in period during which they were compliant to off-loading and to daily application of placebo spray, without major protocol violation. Compliance with the placebo run-in treatment regimen must be "excellent" or "acceptable".
- Glycosylated hemoglobin (HbA1c) below or equal 10% (from a blood sample taken during the placebo run-in period).
- Non-infected target foot DFU of confirmed neuropathic origin with:
- Target DFU appropriately debrided (<10% black and at least 50% of red/pink on a colorimetric scale)
Key exclusion criteria (21 listed)
- Patients who fulfill any of the following criteria are not eligible to be enrolled in the study:
- Active Charcot foot, or inactive Charcot foot, if the target DFU cannot be properly offloaded.
- Ulcers of non-neuropathic origin (e.g., rheumatoid, radiation-related, vasculitis-related ulcers).
- Presence of any foot ulcer (whether or not on the target foot) for which local or systemic antibiotic treatment is required.
- Evidence of skin cancer within or adjacent to the target ulcer.
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 |
|---|---|---|
| Trafermin 0.01% sprayFor ulcers with a maximum diameter (longest axis) of less or equal to 6 cm, the daily dose of trafermin 0.01% spray is 5 puffs (30 microgram) sprayed onto the wound surface. If the maximum diameter (longest axis) of the ulcer is >6 cm, the ulcer should be sprayed in two parts, i.e. 5 puffs (30 microgram) sprayed onto each half of the wound surface | Drug | Matching placebo spray, Trafermin 0.01% spray |
Primary outcome
Wound Closure Rate of Diabetic Foot Ulcers (DFUs) of Neuropathic Origin After a Maximum of 12 Weeks Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition to Best Local Cares
Time frame: 12 weeks
wound closure is defined as 100% reepithelialization of the target DFU, without exudates.
1 secondary outcome
Relative Wound Area Regression of 40% or More at 6 Week
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Jean-Charles Kerihuel, MD study director
VERTICAL
Luc Téot, MD study chair
University Hospital, Montpellier
37 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trafermin 0.01% spray in people with Diabetic Foot Ulcer of Neuropathic Origin, run by Olympus Biotech Corporation at 37 sites in 10 countries.
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 10 inclusion and 21 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 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in Poland, Germany, Netherlands, Slovakia, Belgium and 5 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Wound Closure Rate of Diabetic Foot Ulcers (DFUs) of Neuropathic Origin After a Maximum of 12 Weeks Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition to Best Local Cares (time frame: 12 weeks). 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 5 Aug 2014.