Dose-response Relationship Study of S42909 on Leg Ulcer Healing

Venous Leg Ulcer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03077165
• Other study ID #: CL2-42909-016
• Status: Completed
• Phase: Phase 2
• Start date: September 12, 2017
• Est. completion date: January 22, 2020

Study information

• Verified date: September 2020
• Source: Ilkos Therapeutic Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: January 22, 2020
• Est. primary completion date: December 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%.

Related Conditions & MeSH terms

• Leg Ulcer
• Ulcer
• Varicose Ulcer
• Venous Leg Ulcer

Intervention

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.
• 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.
• 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.
• 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.
• 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 Oral Tablet
Matching placebo tablets, per os administration, twice a day taken at the end of the morning and at evening meals.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ilkos Therapeutic Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Canada,  Czechia,  Hungary,  Italy,  Poland,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse Events	Occurring during the double-blind period of the study	Up to 8 weeks
Secondary	Assessment of Laboratory Parameters	Biochemistry, Haematology and Fasting Lipids	Up to 8 weeks