The TRAfermin in Neuropathic Diabetic Foot Ulcer Study - Southern Europe The TRANS-South Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Olympus Biotech Corporation
ClinicalTrials.gov Identifier:
NCT01217463
First received: October 7, 2010
Last updated: April 22, 2013
Last verified: April 2013
  Purpose

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,).


Condition Intervention Phase
Diabetic Foot Ulcer of Neuropathic Origin
Drug: Trafermin 0.01% spray
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Olympus Biotech Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    closure is defined as 100% reepithelialization of the target DFU, without exudate.


Secondary Outcome Measures:
  • Time to reach complete wound closure [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Absolute and relative wound area regression and wound edge migration based on planimetry tracing [ Time Frame: 12 weeks and 24 weeks ] [ Designated as safety issue: No ]
  • Occurrence rate of clinical infection on the target DFU [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Safety of trafermin 0.01% spray [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Rate of amputations on the target DFU [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Maintenance of wound closure/time to re-opening up to 3 months after observed reepithelialization [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • DFU new occurrence/recurrence up to 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • high sensitivity C-Reactive Protein (hs CRP) level variations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To explore biomarkers from target wound fluid (selected centers only) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • To explore the correlation of absolute and relative wound area regression and wound edge migration based on photography in comparison with planimetry tracing [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Frequency of local surgical procedures [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • New wound occurrence [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Reopening rate of closed wounds up to 1, 2, 3 months after reepithelization [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Immunogenicity anti-bFGF antibody [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 201
Study Start Date: November 2010
Study Completion Date: February 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Trafermin 0.01% spray Drug: Trafermin 0.01% spray
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
Placebo Comparator: Matching placebo spray Drug: Trafermin 0.01% spray
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Selection Criteria

Patients who fulfill all of the following criteria (and none of the exclusion criteria described below) are eligible to enter the placebo run-in phase of the study:

  1. Provide written informed consent to participate.
  2. Male or female patients age 18 years or older.
  3. Type 1 or 2 diabetes.
  4. A single full-thickness DFU that has been present for at least 2 weeks.
  5. DFU wound surface area below or equal 34 cm2 on the target foot.
  6. No exposure of bone in the target DFU.
  7. Neuropathy confirmed by loss of protective sensation to monofilament test (Semmes-Weinstein 5.07 monofilament).
  8. No predominant ischemia requiring further exploration or treatment, and confirmed by either:

    • 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
    • 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

Inclusion Criteria

Patients who fulfill all of the following criteria are eligible for randomization:

  1. All of the selection criteria and none of the exclusion criteria are met.
  2. 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"
  3. Glycosylated hemoglobin (HbA1c) below or equal 10% (from a blood sample taken during the placebo run-in period).
  4. 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
    • 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
  5. Target DFU appropriately debrided (<10% black and at least 50% of red/pink on a colorimetric scale)
  6. 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
  7. 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.

Exclusion Criteria

Patients who fulfill any of the following criteria are not eligible to be enrolled in the study:

  1. Active Charcot foot, or inactive Charcot foot, if the target DFU cannot be properly offloaded.
  2. Ulcers of non-neuropathic origin (e.g., rheumatoid, radiation-related, vasculitis-related ulcers).
  3. Presence of any foot ulcer (whether or not on the target foot) for which local or systemic antibiotic treatment is required.
  4. Evidence of skin cancer within or adjacent to the target ulcer.
  5. 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.
  6. 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).
  7. 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.
  8. Morbid obesity, defined as body mass index (BMI) above or equal 45kg/m2.
  9. Clinically significant medical conditions, in the investigator's opinion, that could impair wound healing (e.g. hepatic impairment, immunocompromised patients).
  10. Severe renal failure, defined as requirement for hemodialysis or peritoneal dialysis.
  11. Females who are pregnant or breastfeeding, or who are of childbearing potential and not practicing a medically approved method of contraception.
  12. Concomitant treatment with high dose oral or parenteral corticosteroids, defined as a daily dose of at least 7.5 mg prednisone or equivalent.
  13. Participation in another clinical study within the previous 3 months.
  14. Current participation in another clinical study with any drug or device.
  15. History of drug or alcohol abuse within the previous year.
  16. Concurrent severe psychiatric disease (including severe depressive disorder).
  17. Known intolerance to the IMP or to any of its excipients.
  18. Known to be uncooperative or noncompliant.
  19. 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).
  20. Any other condition which, in the opinion of the investigator, would render the patient unsuitable for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217463

Locations
Czech Republic
Ostrava- Vitkovice, Czech Republic, 70300
Prague, Czech Republic, 14021
Prague, Czech Republic, 10034
Prague, Czech Republic, 15006
Prague, Czech Republic, 18200
France
Bron, France
Lisieux, France
Montpellier, France
Hungary
Budapest, Hungary, 1097
Budapest, Hungary, 1036
Budapest, Hungary, 1095
Kisvárda, Hungary
Szeged, Hungary
Szekszárd, Hungary
Sátoraljaújhely, Hungary
Italy
Abbiategrasso, Italy
Campobasso, Italy
Milan, Italy
Montfalcone, Italy
Padua, Italy
Paola, Italy
Pisa, Italy
Pistoia, Italy
Rome, Italy
Sponsors and Collaborators
Olympus Biotech Corporation
Investigators
Study Director: Jean-Charles Kerihuel, MD VERTICAL
Study Chair: Luc Téot, MD Montpellier University Hospital
  More Information

No publications provided

Responsible Party: Olympus Biotech Corporation
ClinicalTrials.gov Identifier: NCT01217463     History of Changes
Other Study ID Numbers: TFM-CL3-001, 2010-021014-33
Study First Received: October 7, 2010
Last Updated: April 22, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Olympus Biotech Corporation:
Diabetic foot
Neuropathic
Wound
Growth factor

Additional relevant MeSH terms:
Ulcer
Foot Ulcer
Diabetic Foot
Pathologic Processes
Foot Diseases
Skin Diseases
Leg Ulcer
Skin Ulcer
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies

ClinicalTrials.gov processed this record on July 28, 2014