Dose-response Relationship Study of S42909 on Leg Ulcer Healing

A 10-week Randomized, Double-blind, Placebo-controlled, Prospective, International, Multicentre, Phase IIa Study of S42909 on Leg Ulcer Healing.

Dose-response relationship study of S42909 on leg ulcer healing after oral repeated administration in patients with active venous leg ulcer.

Study Overview

• Status: Completed
• Conditions: Venous Leg Ulcer
• Intervention / Treatment: Drug: S42909 100 mg; Drug: S42909 200 mg; Drug: S42909 400 mg; Drug: S42909 800 mg; Drug: S42909 1200 mg; Drug: Placebo Oral Tablet

Detailed Description

S42909 is an inhibitor of β-Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase which also inhibits vascular leukocyte adhesion to endothelial cells, Matrix Metalloproteinase-2 (MMP-2) and Plasminogen Activator Inhibitor-1 (PAI-1) activity. It is proposed for development in the treatment of venous and mixed leg ulcers.

This proof of concept study is a randomized, double-blind, placebo-controlled, multicenter, Phase IIa trial to evaluate the dose response of S42909 for the treatment of venous leg ulcers.

Patients suffering from chronic venous disease and having at least one active venous leg ulcer will be selected at the selection visit (ASSE). One Reference Ulcer (RU) defined as the largest ulcer in size that is fitting the area selection criteria will be established. At ASSE, a first picture will be taken before cleansing and debridement and a second picture will be taken after cleansing and debridement. The investigator will check that the selection RU area is compliant with the selection criteria. Patients will start the selection period and will be switched from their current pharmacological and/or local treatment (if any) for venous leg ulcer to local wound care with sterile saline solution or sterile water, "non-active" dressings and standardized compression (same strength and type of compression). They will be administrated the placebo selection treatment for a period of fourteen days.

Three (or four) working days before the inclusion visit, the participants will come to the site for a RU picture in order to get the RU area central measurement for inclusion visit (W000).

At W000, the investigator will check that the inclusion RU area is compliant with the inclusion criteria. The investigator will also check that the participant is compliant with the selection treatment and stockings wearing.

All participants found to be eligible for inclusion will be randomized to one of the following six groups - S42909: 100, 200, 400, 800 or 1200 mg per day- or placebo.

The participants will enter a 6 weeks ambulatory Investigational Medicinal Product (IMP) treatment period on top of standard of care (standardized compression and local wound care with sterile saline solution or sterile water and "non-active" dressing) followed by a 2 weeks follow-up period of standard of care only. During this period the participants will return to the investigator's site for intermediate visits after one week (W001), two weeks (W002), three weeks (W003), four weeks (W004), six weeks (W006) and eight weeks (W008). Participants will continue receiving standardized compression therapy and local wound care (sterile saline solution or sterile water and "non-active" dressing) until the end of the study (W008).

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aire, Argentina, C1115AAE
    • Centro Dr Bottini de flebologia y estetica
  • La Plata, Argentina, B1900AXI
    • Hospital Italiano de La Plata
  • Ramos Mejía, Argentina, B1704ETD
    • Dim Clinica Privada
  • Rosario, Argentina, 2000
    • Sanatorio Mapaci
• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck Universitaetsklinik für Gefässchirurgie
  • Wien, Austria, 1080
    • VENEX Zentrum fuer minimal invasive Venentherapie
  • Wien, Austria, 1090
    • Medizinische Universitaet Wien AKH- Dermatologie
• Brazil
  • Botucatu, Brazil, 18618-686
    • Faculdade de Medicina de Botucatu
  • Porto Alegre, Brazil, 90035-003
    • Hospital das Clinicas de Porto Alegre
  • Santo André, Brazil, 09060-870
    • Faculdade de Medicina do ABC Cepes
  • São Bernardo Do Campo, Brazil, 09715-090
    • Centro Multidisciplinar de Estudos Clinicos CEMEC
  • São Paulo, Brazil, 04037-002
    • Hospital Sao Paulo
  • Teixeira Soares, Brazil, 99010-080
    • Hospital São Vicente de Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Alberta Health Services
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Parkwood Institute
    • Mississauga, Ontario, Canada, L4Y 1A6
      • Toronto Regional Dermatology & Wound Healing Clinic
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Civic Campus
    • Ottawa, Ontario, Canada, K2G 6E2
      • Centrepoint Medical Center
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • York Dermatology Center
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• Czechia
  • Brno, Czechia, 602 00
    • I. Dermatovenerologicka Klinika
  • Hodonín, Czechia, 69501
    • MATMED s.r.o.
  • Jihlava, Czechia, 586 33
    • Nemocnice Jihlava Chirurgie A
  • Třebíč, Czechia, 674 01
    • Nemocnice Trebic Kozni oddeleni p.o.
  • Zlín, Czechia, 76001
    • Angiocor s.r.o.
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvédség Egészségügyi Központ
  • Budapest, Hungary, 1076
    • Péterfy Sándor utcai Kórház
  • Budapest, Hungary, 1097
    • Egyesitett Szent Istvan es Szent
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinsky Korhaz
  • Budapest, Hungary, 1134
    • Magyar Honvedseg Egeszsegugyi
  • Debrecen, Hungary, 4012
    • Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
  • Kecskemét, Hungary, 6000
    • Bacs-kiskun Megyei Korhaz
  • Nyiregyhaza, Hungary, 4400
    • Jósa András Oktatókórház
  • Pécs, Hungary, 7632
    • Pesi Tudomanyegyetem Klnikai Kozpont
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem Borgyogyaszati es Allergologiai Klinica
• Italy
  • Avellino, Italy, 83100
    • Azienda Ospedaliera San Giuseppe Moscati Medicina interna
  • Bassano Del Grappa, Italy, 36061
    • Ospedale San Bassiano - Azienda ULSS n. 7 Pedemontana - Ambulatorio di Vulnologia
  • Castelfranco Veneto, Italy, 31033
    • Ospedale San Giacomo Apostolo Castelfranco Veneto - U.O. Angiologia
  • Catania, Italy, 95124
    • Policlinico Vittorio Emanuele - Presidio Ospedaliero Vittorio Emanuele
  • Padova, Italy, 35128
    • Azienda Ospedaliero Universitaria di Padova U.O. Angiologia - Medicina Vascolare
  • Pozzilli, Italy, 86077
    • Istituto Neurologico Mediterraneo NEUROMED U.O.C. Chirurgia Vascolare ed Endovascolare
  • Soverato, Italy, 88068
    • Ospedale Basso Ionio ASPCZ U.O.C. Chirurgia Generale, P.O. di Soverato
  • Viterbo, Italy, 01100
    • Ospedale Belcolle - U.O Angiologia
• Poland
  • Białystok, Poland, 15-879
    • Clinicmed Daniluk
  • Bydgoszcz, Poland, 85-094
    • Szpital Uniwersytecki nr 1 im. Antoniego Jurasza
  • Lublin, Poland, 20-081
    • Medical Academy of Lublin
  • Poznań, Poland, 60-848
    • SP Szpital Kliniczny Nr1
  • Warsaw, Poland, 02-034
    • Klinika Flebologii
• Slovakia
  • Bardejov, Slovakia, 085 01
    • ALIAN, s.r.o., Poliklinika ČK plus
  • Bratislava, Slovakia, 84102
    • BeneDerma
  • Bratislava, Slovakia, 85101
    • Derm-Therapy
  • Dunajská Streda, Slovakia, 929 01
    • M.M.-Angio spol. s r.o., Angiologicka ambulancia
  • Košice, Slovakia, 040 01
    • ANGIOCARE, s.r.o.
  • Poprad, Slovakia, 058 01
    • ALIAN, s.r.o., Angiologická ambulancia
  • Svidník, Slovakia, 089 01
    • Dermatovenerologicke oddelenie SANARE, spol. s r.o.
  • Svidník, Slovakia, 08901
    • Nemocnica arm. generala L. Svobodu Svidnik
  • Trnava, Slovakia, 917 01
    • MEDENA s.r.o., Angiologicka ambulancia
  • Žilina, Slovakia, 010 01
    • MEDIVASA, s.r.o.
• Spain
  • Avilés, Spain, 33402
    • Fundacion Hospital de Aviles
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08227
    • Consorci Sanitari de Terrassa - Hospital de Terrassa
  • Getafe, Spain, 280902
    • Hospital Universitario de Getafe
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28003
    • Hospital de la Cruz Roja de Madrid
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario
  • Valencia, Spain, 46940
    • Hospital de Manises
• United States
  • California
    • Carlsbad, California, United States, 92009
      • ILD Research Center
    • Carmichael, California, United States, 95608
      • Center for Clinical Research Inc.
    • Castro Valley, California, United States, 94546
      • Center for Clinical Research Inc.
    • Fresno, California, United States, 93710
      • Limb Preservation Platform, Inc.
    • Los Angeles, California, United States, 90057
      • Foot and Ankle Clinic
    • Redwood City, California, United States, 94063
      • Stanford Hospitals and Clinics
    • San Francisco, California, United States, 94115
      • Center for Clinical Research Inc.
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital Wound Center
  • Idaho
    • Boise, Idaho, United States, 83702
      • St. Luke's Intermountain Research Center
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Podiatry 1st
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Advanced Foot & Ankle Center
  • Pennsylvania
    • Kittanning, Pennsylvania, United States, 16201
      • The Snyder Institute for Vascular Health and Research
    • Pittsburgh, Pennsylvania, United States, 15219
      • D&P Medical Group, LLC
    • Pittsburgh, Pennsylvania, United States, 15219
      • Serena Group Research Foundation

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:

• Caucasian (defined for this study as having 2 Caucasian parents), men or women
• Age ≥ 18 years old
• 18.5 kg/m2 ≤ BMI ≤ 45.0 kg/m2 (= Weight (kg) / height² (m²))
• Patients with chronic venous disease documented by imaging to detect a venous disorder in one or both the sub- and extra-fascial venous systems. The examination performed within 6 months before selection can be used.
• Patients with at least one active venous leg ulcer localised in the gaiter area (CEAP C6) diagnosed or reoccurred for more than 6 weeks and less than 2 years at selection and 3 cm away from other ulcers. Patients with bilateral ulcerations or multiple ulcerations on one or both legs are eligible for selection.
• Size of Reference Ulcer (defined as the largest ulcer in size that is fitting the area selection criteria) should be ≥ 5 cm2 and ≤ 100 cm2 at the selection visit and ≥ 4.5 cm2 and ≤ 100 cm2 at the inclusion visit (measured by transparent sheet and confirmed with the digital 3D imaging device).
• Ankle Brachial Pressure Index (ABPI) ≥ 0.8 and ≤ 1.3 measured by Doppler ultrasound.

Exclusion Criteria:

• Unlikely or unwilling to be compliant to standardized compression recommendation, study medication and visits, previous records of poor compliance to compression stockings.
• Inadequately controlled type 1 and type 2 diabetes with an HbA1c > 8%.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; S42909 dose 100 mg p.o., 50 mg bid	Drug: S42909 100 mg; 50 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.
EXPERIMENTAL: Group B; S42909 dose 200 mg p.o., 100 mg bid	Drug: S42909 200 mg; 50 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.
EXPERIMENTAL: Group C; S42909 dose 400 mg p.o., 200 mg bid	Drug: S42909 400 mg; 200 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.
EXPERIMENTAL: Group D; S42909 dose 800 mg p.o., 400 mg bid	Drug: S42909 800 mg; 200 mg Film-coated tablets per os administration,twice a day taken at the end of the morning and at evening meals.
EXPERIMENTAL: Group E; S42909 dose 1200 mg p.o., 600 mg bid	Drug: S42909 1200 mg; 200 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.
PLACEBO_COMPARATOR: Group F; Placebo p.o. bid	Drug: Placebo Oral Tablet; Matching placebo tablets, per os administration, twice a day taken at the end of the morning and at evening meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Reduction of Reference Ulcer Area After 4 Weeks of Treatment on Top of Standard of Care Compared With Baseline Reference Ulcer Area (W000) Assessed During Study Visits	Change of reference Ulcer area measurement in cm^2 from Baseline to Week 4.	Baseline and Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Occurring during the double-blind period of the study	Up to 8 weeks
Assessment of Laboratory Parameters	Biochemistry, Haematology and Fasting Lipids	Up to 8 weeks

Collaborators and Investigators

• Sponsor: Ilkos Therapeutic Inc.
• Investigators: Principal Investigator: Eberhard Rabe, Professor, Department of Dermatology University of Bonn

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 12, 2017
• Primary Completion (ACTUAL): December 12, 2019
• Study Completion (ACTUAL): January 22, 2020

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: March 6, 2017
• First Posted (ACTUAL): March 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: CL2-42909-016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No