Clinical trial NCT03077165: Dose-response Relationship Study of S42909 on Leg Ulcer Healing
Official title: A 10-week Randomized, Double-blind, Placebo-controlled, Prospective, International, Multicentre, Phase IIa Study of S42909 on Leg Ulcer Healing.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Leg Ulcer
Lead sponsor: Ilkos Therapeutic Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-10
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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%.

Primary outcomes:
measure: 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
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Adverse Events
timeFrame: Up to 8 weeks
measure: Assessment of Laboratory Parameters
timeFrame: Up to 8 weeks
Other outcomes:
Locations:
city: Carlsbad
country: United States
facility: ILD Research Center
state: California
city: Carmichael
country: United States
facility: Center for Clinical Research Inc.
state: California
city: Castro Valley
country: United States
facility: Center for Clinical Research Inc.
state: California
city: Fresno
country: United States
facility: Limb Preservation Platform, Inc.
state: California
city: Los Angeles
country: United States
facility: Foot and Ankle Clinic
state: California
city: Redwood City
country: United States
facility: Stanford Hospitals and Clinics
state: California
city: San Francisco
country: United States
facility: Center for Clinical Research Inc.
state: California
city: Miami
country: United States
facility: University of Miami Hospital Wound Center
state: Florida
city: Boise
country: United States
facility: St. Luke's Intermountain Research Center
state: Idaho
city: Belleville
country: United States
facility: Podiatry 1st
state: Illinois
city: Las Vegas
country: United States
facility: Advanced Foot & Ankle Center
state: Nevada
city: Kittanning
country: United States
facility: The Snyder Institute for Vascular Health and Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: D&P Medical Group, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Serena Group Research Foundation
state: Pennsylvania
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Dr Bottini de flebologia y estetica
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: Ramos Mejía
country: Argentina
facility: DIM Clinica Privada
city: Rosario
country: Argentina
facility: Sanatorio Mapaci
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck Universitaetsklinik für Gefässchirurgie
city: Wien
country: Austria
facility: VENEX Zentrum fuer minimal invasive Venentherapie
city: Wien
country: Austria
facility: Medizinische Universitaet Wien AKH- Dermatologie
city: Botucatu
country: Brazil
facility: Faculdade de Medicina de Botucatu
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC Cepes
city: São Bernardo Do Campo
country: Brazil
facility: Centro Multidisciplinar de Estudos Clinicos CEMEC
city: São Paulo
country: Brazil
facility: Hospital Sao Paulo
city: Teixeira Soares
country: Brazil
facility: Hospital Sao Vicente de Paulo
city: Calgary
country: Canada
facility: Alberta Health Services
state: Alberta
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Mississauga
country: Canada
facility: Toronto Regional Dermatology & Wound Healing Clinic
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Civic Campus
state: Ontario
city: Ottawa
country: Canada
facility: Centrepoint Medical Center
state: Ontario
city: Richmond Hill
country: Canada
facility: York Dermatology Center
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Brno
country: Czechia
facility: I. Dermatovenerologicka Klinika
city: Hodonín
country: Czechia
facility: MATMED s.r.o.
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava Chirurgie A
city: Třebíč
country: Czechia
facility: Nemocnice Trebic Kozni oddeleni p.o.
city: Zlín
country: Czechia
facility: Angiocor s.r.o.
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Budapest
country: Hungary
facility: Peterfy Sandor Utcai Korhaz
city: Budapest
country: Hungary
facility: Egyesitett Szent Istvan es Szent
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinsky Korhaz
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Oktatokorhaz
city: Pécs
country: Hungary
facility: Pesi Tudomanyegyetem Klnikai Kozpont
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Borgyogyaszati es Allergologiai Klinica
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati Medicina interna
city: Bassano Del Grappa
country: Italy
facility: Ospedale San Bassiano - Azienda ULSS n. 7 Pedemontana - Ambulatorio di Vulnologia
city: Castelfranco Veneto
country: Italy
facility: Ospedale San Giacomo Apostolo Castelfranco Veneto - U.O. Angiologia
city: Catania
country: Italy
facility: Policlinico Vittorio Emanuele - Presidio Ospedaliero Vittorio Emanuele
city: Padova
country: Italy
facility: Azienda Ospedaliero Universitaria di Padova U.O. Angiologia - Medicina Vascolare
city: Pozzilli
country: Italy
facility: Istituto Neurologico Mediterraneo NEUROMED U.O.C. Chirurgia Vascolare ed Endovascolare
city: Soverato
country: Italy
facility: Ospedale Basso Ionio ASPCZ U.O.C. Chirurgia Generale, P.O. di Soverato
city: Viterbo
country: Italy
facility: Ospedale Belcolle - U.O Angiologia
city: Białystok
country: Poland
facility: ClinicMed Daniluk
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. Antoniego Jurasza
city: Lublin
country: Poland
facility: Medical Academy of Lublin
city: Poznań
country: Poland
facility: SP Szpital Kliniczny Nr1
city: Warsaw
country: Poland
facility: Klinika Flebologii
city: Bardejov
country: Slovakia
facility: ALIAN, s.r.o., Poliklinika ČK plus
city: Bratislava
country: Slovakia
facility: BeneDerma
city: Bratislava
country: Slovakia
facility: Derm-Therapy
city: Dunajská Streda
country: Slovakia
facility: M.M.-Angio spol. s r.o., Angiologicka ambulancia
city: Košice
country: Slovakia
facility: ANGIOCARE, s.r.o.
city: Poprad
country: Slovakia
facility: ALIAN, s.r.o., Angiologická ambulancia
city: Svidník
country: Slovakia
facility: Dermatovenerologicke oddelenie SANARE, spol. s r.o.
city: Svidník
country: Slovakia
facility: Nemocnica arm. generala L. Svobodu Svidnik
city: Trnava
country: Slovakia
facility: MEDENA s.r.o., Angiologicka ambulancia
city: Žilina
country: Slovakia
facility: MEDIVASA, s.r.o.
city: Avilés
country: Spain
facility: Fundacion Hospital de Aviles
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Consorci Sanitari de Terrassa - Hospital de Terrassa
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
city: Madrid
country: Spain
facility: Hospital de la Cruz Roja de Madrid
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario
city: Valencia
country: Spain
facility: Hospital de Manises
Study officials:
affiliation: Department of Dermatology University of Bonn
name: Eberhard Rabe, Professor
role: PRINCIPAL_INVESTIGATOR
References: