Diabetic Foot Ulcer of Neuropathic OriginPhase 3TRANS-SouthNCT01217463

The TRAfermin in Neuropathic Diabetic Foot Ulcer Study - Southern Europe The TRANS-South 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 24 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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: 201 participants
Where: 24 sitesin 4 countries
Study dates: Nov 2010to Feb 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 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 45kg/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

24 sites in 4 countries.

Country

City, postcode or hospital

24 sites in 4 countries

Italy9 sites

Study site
Abbiategrasso
Study site
Campobasso
Study site
Milan
Study site
Montfalcone
Study site
Padua
Study site
Paola
Study site
Pisa
Study site
Pistoia
Study site
Rome

Other trials in Italy

Hungary7 sites

Study site
Budapest, 1036
Study site
Budapest, 1095
Study site
Budapest, 1097
Study site
Kisvárda
Study site
Sátoraljaújhely
Study site
Szeged
Study site
Szekszárd

Other trials in Hungary

Czechia5 sites

Study site
Ostrava- Vitkovice, 70300
Study site
Prague, 10034
Study site
Prague, 14021
Study site
Prague, 15006
Study site
Prague, 18200

Other trials in Czechia

France3 sites

Study site
Bron
Study site
Lisieux
Study site
Montpellier

Other trials in France

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.

The investigators 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 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 30 investigational sites in an estimated 4 countries in Europe (Czech Republic,France,Hungary,Italy,).

Conditions: Diabetic Foot Ulcer of Neuropathic Origin
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 groups in NCT01217463
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 Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition
Wound closure is defined as 100% reepithelialization of the target DFU, without exudate.
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.

Nov 2010Feb 2013

First posted8 Oct 2010 (estimated)
Study startNov 2010
Primary completionMar 2012
Study completionFeb 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: 201 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01217463
Sponsor's protocol ID: TFM-CL3-001
Other IDs: 2010-021014-33
Acronym: TRANS-South
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: NCT01217463
Acronym / sponsor ID: TRANS-South / TFM-CL3-001
Conditions: Diabetic Foot Ulcer of Neuropathic Origin
Keywords: Diabetic foot, Neuropathic, Wound, Growth factor
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 201 participants (actual)
Lead sponsor: Olympus Biotech CorporationIndustry (pharma, biotech, devices)
Study start: Nov 2010
Primary completion: Mar 2012 (actual)
Study completion: Feb 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.

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 Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition
Time frame: 12 weeks
Wound closure is defined as 100% reepithelialization of the target DFU, without exudate.

1 secondary outcome

Relative Wound Area Regression of 40% or More at 6 Week
Time frame: 6 weeks

Results and safety

Results posted to the registry on 5 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Trafermin	99	86
Placebo	102	94

Primary outcome: Wound Closure Rate of Diabetic Foot Ulcers (DFUs) of Neuropathic Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition

Time frame: 12 weeks. Number. Unit: percentage of participants

Measure	Trafermin n = 99	Placebo n = 102
Value	14.1	10.8

Trafermin vs Placebo: Odds Ratio (OR): 1.44 (95% CI 0.60 to 3.43), p = 0.4109, Regression, Logistic

Population analysed: The primary analysis of the efficacy criteria was conducted on the ITT population.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Primary Treatment Emergent Adverse Event: adverse events that occurred after starting the treatment with the study medication until the end of primary follow up period up to 24 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Trafermin	23 of 99 (23.2%)	20 of 99 (20.2%)	Not reported
Placebo	17 of 102 (16.7%)	21 of 102 (20.6%)	Not reported

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

24 sites in 4 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 24 sites in 4 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 24 sites in Italy, Hungary, Czechia, France. 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 Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition (time frame: 12 weeks). 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 NCT01217463.

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.