Trial Outcomes & Findings for The TRAfermin in Neuropathic Diabetic Foot Ulcer Study - Southern Europe The TRANS-South Study (NCT NCT01217463)

NCT ID: NCT01217463

Last Updated: 2014-08-05

Results Overview

Wound closure is defined as 100% reepithelialization of the target DFU, without exudate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

12 weeks

Results posted on

2014-08-05

Participant Flow

Participant milestones

Participant milestones
Measure	Trafermin 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 Matching placebo 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
Overall Study STARTED	99	102
Overall Study COMPLETED	86	94
Overall Study NOT COMPLETED	13	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Trafermin 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 Matching placebo 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
Overall Study Adverse Event	8	5
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	3	0
Overall Study Surgery on the Target Limb	0	1
Overall Study Patient Non-compliant	1	0
Overall Study Other	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trafermin n=99 Participants Trafermin 0.01% spray	Placebo n=102 Participants Matching placebo spray	Total n=201 Participants Total of all reporting groups
Age, Continuous	62.0 years STANDARD_DEVIATION 10.0 • n=5 Participants	61.7 years STANDARD_DEVIATION 9.4 • n=7 Participants	61.9 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	86 Participants n=7 Participants	170 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=5 Participants	100 Participants n=7 Participants	199 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Wound size ≤5cm^2	77 participants n=5 Participants	80 participants n=7 Participants	157 participants n=5 Participants
Wound size >5cm^2	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Peripheral blood perfusion Impaired	36 participants n=5 Participants	38 participants n=7 Participants	74 participants n=5 Participants
Peripheral blood perfusion Normal	63 participants n=5 Participants	64 participants n=7 Participants	127 participants n=5 Participants
BMI	30.91 Kg/m2 STANDARD_DEVIATION 4.42 • n=5 Participants	30.65 Kg/m2 STANDARD_DEVIATION 5.00 • n=7 Participants	30.78 Kg/m2 STANDARD_DEVIATION 4.71 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

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

Wound closure is defined as 100% reepithelialization of the target DFU, without exudate.

Outcome measures

Outcome measures
Measure	Trafermin n=99 Participants Trafermin 0.01% spray	Placebo n=102 Participants Matching placebo spray
Wound Closure Rate of Diabetic Foot Ulcers (DFUs) of Neuropathic Topical Daily Application of Trafermin 0.01% Spray Compared With Placebo, in Addition	14.1 percentage of participants	10.8 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks

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

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.

Outcome measures

Outcome measures
Measure	Trafermin n=99 Participants Trafermin 0.01% spray	Placebo n=102 Participants Matching placebo spray
Relative Wound Area Regression of 40% or More at 6 Week	60.9 percentage of participants	52.9 percentage of participants

Adverse Events

Trafermin

Serious events: 23 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 17 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Trafermin n=99 participants at risk Trafermin 0.01% spray	Placebo n=102 participants at risk Matching placebo spray
Infections and infestations Diabetic foot infection	9.1% 9/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	9.8% 10/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Metabolism and nutrition disorders Diabetic foot	11.1% 11/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	10.8% 11/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.

Additional Information

Mr. Akira Kondo, Manager, Clinical R&D

Olympus France S.A.S

Phone: +33-1-4560-6849

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI have no implicit or explicit rights to publish study data and results of their services.
Publication restrictions are in place

Restriction type: OTHER

Measure	Trafermin n=99 participants at risk Trafermin 0.01% spray	Placebo n=102 participants at risk Matching placebo spray
Blood and lymphatic system disorders Anemia	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Cardiac disorders Angina pectoris	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Cardiac disorders Cardiac failure acute	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Cardiac disorders Cardiac failure chronic	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Cardiac disorders Coronary artery stenosis	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Eye disorders Blindness	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Eye disorders Retinal hemorrhage	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Gastrointestinal disorders Edema peripheral	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Abscess	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Diabetic foot infection	3.0% 3/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	2.9% 3/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Erysipelas	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	2.0% 2/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Gangrene	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Osteomyelitis	4.0% 4/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	3.9% 4/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Pneumonia	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Postoperative wound infection	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Infections and infestations Sepsis	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Injury, poisoning and procedural complications Wrist fracture	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Surgical and medical procedures Leg amputation	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Surgical and medical procedures Skin graft	0.00% 0/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	2.0% 2/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Surgical and medical procedures Toe amputation	3.0% 3/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Vascular disorders Peripheral arterial occlusive disease	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Vascular disorders Peripheral embolism	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.00% 0/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.
Vascular disorders Peripheral ischemia	1.0% 1/99 • 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. The safety population included all patients who were randomized and exposed to the study treatment.	0.98% 1/102 • 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. The safety population included all patients who were randomized and exposed to the study treatment.