A Dose Finding Study of Topically Applied I-020201 as an Adjunct to Good Standard-of-care in Patients With Chronic Diabetic Foot Ulcers (DFU)

A Randomized, Multi-center, Controlled, Parallel Group, Dose Finding Study of the Efficacy and Safety of Topically Applied I-020201 as an Adjunct to Good Standard-of-care Versus Good Standard-of-care Alone in Patients With Chronic Diabetic Foot Ulcers

Although major improvements in the management and treatment of diabetic foot ulcers have been made, the clinical and financial burden of such long-term wounds is still high and is likely to increase as the general population ages. The large population affected by diabetic foot ulcers and the high rates of failure ending with amputation even with the best therapeutic regimens have resulted in the development of new therapies. I-020201 is a bioactive therapy intended for topical treatment of hard-to-heal diabetic foot ulcers, stimulating the granulation tissue formation. This study aims to evaluate the safety and efficacy of I-020201 in adjunct to good standard of care in patients with chronic diabetic foot ulcer.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Procedure: Good Standard of Care (GSoC); Biological: Vehicle; Biological: I-020201

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Hradec Králové, Czech Republic, 500 05
    • Diabetologické centrum, I. Interní klinika FN Hradec Králové, Fakultní nemocnice Hradec Králové (21)
  • Praha, Czech Republic, 150 06
    • Interní klinika 2. Lékařské fakulty UK a FN Motol, Fakultní nemocnice Motol (22)
  • Zlín, Czech Republic, 760 01
    • Lékařský dum Ormiga Angiologická a diabetologická ambulance (20)
  • Ústí nad Labem, Czech Republic, 401 13
    • Oddelení diabetologie - Podiatricka ambulance Krajská zdravotní a.s.- Masarykova nemocnice v Ústí nad Labem o.z. (23)
• Germany
  • Böblingen, Germany, 71031
    • Klinikum Sindelfingen-Böblingen (01)
  • Karlsbad, Germany, 76307
    • SRH Klinikum Karlsbad-Langensteinbach (04)
  • Stuttgart, Germany, 70191
    • Klinikum Stuttgart Bürgerhospital (03)
  • Tübingen, Germany, 72076
    • Universitätsklinik Tübingen Chirugische Poliklinik (02)
• Hungary
  • Budapest, Hungary, 1027
    • Budai Irgalmasrendi Közhasznú Non-Profit Kft (35)
  • Budapest, Hungary, 1097
    • Fõvárosi Önkormányzat Egyesített Szent István és Szent László Kórház - Rendelõintézet Sebészeti Osztály (32)
  • Budapest, Hungary, 1115
    • Fővárosi Önkormányzat Szent Imre Kórház Operativ Szakmák Mátrix Szervezete Általános Sebészeti Profil (33)
  • Esztergom, Hungary, 2500
    • Esztergom Város Önkormányzat Vaszary Kolos Kórház Sebészeti Osztály (34)
  • Kaposvar, Hungary, 7400
    • Kaposi Mór Oktató Kórház (38)
  • Kecskemét, Hungary, 6000
    • Bács-Kiskun Megyei Önkormányzat Kórháza Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza, 2. Belgyógyászat (31)
  • Miskolc, Hungary, 3526
    • Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház Érsebészeti Osztály (30)
  • Pécs, Hungary, 7623
    • PTE Klinikai Központ Érsebészeti Klinikai Tanszék (36)
  • Szeged, Hungary, 6720
    • SZTE Szent-Györgyi Albert Klinikai Centrum (37)
• Romania
  • Bucharest, Romania, 020475
    • Institutul Naţional de Diabet, Nutriţie şi Boli Metabolice "Prof. Dr. N. C. Paulescu" (42)
  • Cluj-Napoca, Romania, 400006
    • Spitalul Clinic Judeţean de Urgenţă Cluj (43)
  • Tg Mures, Romania, 540342
    • Spitalul Clinic Judeţean Mureş, Clinica de Dermatologie (40)
  • Tg. Mures,, Romania, 540530
    • Cabinet Medical Individual DermaMed (41)
  • Timisoara, Romania, 300723
    • Spitalul Clinic Judetean de Urgenta Timisoara (45)
• Russian Federation
  • Moscow, Russian Federation, 115280
    • Moscow City Clinical Hospital # 13 (11)
  • Moscow, Russian Federation, 115432
    • Moscow State University of Public Health "City Clinical (17)
  • Moscow, Russian Federation, 117049
    • Department of Endocrinology and Diabetes, Russian State Medical University, Moscow City Clinical Hospital # 1 (15)
  • Moscow, Russian Federation, 119034
    • Department of Diabetic Foot Endocrinology dispensary (12)
  • Moscow, Russian Federation, 119992
    • Endocrinology Clinic of the State Educational Institute of High Professional Education (18)
  • Moscow, Russian Federation, 123448
    • Federal State Institution "Federal Bureau of Medical Social Expertise" (10)
  • Moscow, Russian Federation, 127644
    • Moscow Clinical Hospital # 81 (14)
• Serbia
  • Belgrade, Serbia, 11 000
    • Klinički centar Srbije, Institut za endokrinologiju, dijabetes i bolesti metabolizma (51)
  • Kragujevac, Serbia, 34 000
    • Clinical Centre Kragujevac (54)
  • Nis, Serbia, 18000
    • Clinical Centre Nis (50)
  • Novi Sad, Serbia, 21 000
    • Clinical Centre of Vojvodina (53)
  • Valjevo, Serbia, 14 000
    • Health Centre Valjevo (52)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female, aged ≥ 18 years
• given written informed consent
• female of childbearing potential with a negative result from the pregnancy test at screening who agrees to use an acceptable birth control method (hormonal or IUD) or abstinence throughout the trial
• Type 1 or Type 2 Diabetes mellitus with HbA1c =< 12%
• with only one diabetic foot ulcer on the foot to be treated on or below the ankle

Exclusion Criteria:

• pregnant or breast-feeding
• known or suspected allergies to any of the components of the I-020201
• uncontrolled anemia (Hb < 9 g/dL in females and < 10 g/dL in males)
• hypoalbuminemia (albumin < 3 g/dL)
• overtly infected target ulcer (as judged by investigator)
• highly exuding wounds (wounds that require a daily dressing change)
• osteomyelitis
• systemic infections
• acute Charcot foot and severe chronic Charcot deformity
• ABPI < 0.7 or ankle systolic pressure < 70 mm Hg

• one of the following findings (only 1 out of 3 tests is required):

  • on Doppler waveform analysis on the dorsalis pedis and posterior tibial arteries a monophasic or biphasic flow (with loss of reverse flow) in either foot artery, or
  • a toe: brachial index < 0.7, or
  • transcutaneous oxygen pressure (TcpO2) < 40 mm Hg
• suspicion, presence or history of systemic or local cancer or tumor of any kind

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Good Standard of Care (GSoC); Twice per week	Procedure: Good Standard of Care (GSoC); Procedural treatment twice per week
EXPERIMENTAL: GSoC + vehicle; Twice per week	Procedure: Good Standard of Care (GSoC); Procedural treatment twice per week; Biological: Vehicle; Topical fibrin as an adjunct to GSoC twice per week
EXPERIMENTAL: GSoC + I-020201 (33microg); Twice per week	Procedure: Good Standard of Care (GSoC); Procedural treatment twice per week; Biological: I-020201; Topical treatment with 3 different concentrations as an adjunct to GSoC twice per week
EXPERIMENTAL: GSoC + I-020201 (100microg); Twice per week	Procedure: Good Standard of Care (GSoC); Procedural treatment twice per week; Biological: I-020201; Topical treatment with 3 different concentrations as an adjunct to GSoC twice per week
EXPERIMENTAL: GSoC + I-020201 (300microg); Twice per week	Procedure: Good Standard of Care (GSoC); Procedural treatment twice per week; Biological: I-020201; Topical treatment with 3 different concentrations as an adjunct to GSoC twice per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage reduction in ulcer surface area	4 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards)	At 12 and 16 weeks after treatment start
Incidence of complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards)	Within the whole study period (28 weeks after treatment start)
Time to complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards).	At any time during the study
Incidence of treatment failure defined as <30% decrease in ulcer size	After 8 weeks of treatment
Incidence of patients with ulcer recurrence	Up to 16 and 28 weeks after treatment start
Incidence of treatment-related adverse events (systemic and at the target ulcer) and all AEs/SAEs	During the whole study period
Changes in systemic PDGF-AB and antibody levels against TG-PDGF.AB and aprotinin	At 1, 4, 12, 16 and 20 weeks after treatment start
Changes in vital signs, body weight, physical examination and laboratory parameters	Throughout the study and 28 weeks after treatment start

Collaborators and Investigators

• Sponsor: Kuros Biosurgery AG

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: June 5, 2009
• First Submitted That Met QC Criteria: June 5, 2009
• First Posted (ESTIMATE): June 8, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 16, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Diabetic; topical; ulcer; PDGF; GSoC
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: CS I-020201/01