Dose-response Relationship Study of S42909 on Leg Ulcer Healing

NCT ID: NCT03077165

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-12
• Study Completion Date: 2020-01-22

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).

Conditions

Venous Leg Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A

S42909 dose 100 mg p.o., 50 mg bid

Group Type: EXPERIMENTAL

S42909 100 mg

Intervention Type: DRUG

50 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.

Group B

S42909 dose 200 mg p.o., 100 mg bid

Group Type: EXPERIMENTAL

S42909 200 mg

Intervention Type: DRUG

50 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.

Group C

S42909 dose 400 mg p.o., 200 mg bid

Group Type: EXPERIMENTAL

S42909 400 mg

Intervention Type: DRUG

200 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.

Group D

S42909 dose 800 mg p.o., 400 mg bid

Group Type: EXPERIMENTAL

S42909 800 mg

Intervention Type: DRUG

200 mg Film-coated tablets per os administration,twice a day taken at the end of the morning and at evening meals.

Group E

S42909 dose 1200 mg p.o., 600 mg bid

Group Type: EXPERIMENTAL

S42909 1200 mg

Intervention Type: DRUG

200 mg Film-coated tablets per os administration, twice a day taken at the end of the morning and at evening meals.

Group F

Placebo p.o. bid

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Placebo Oral Tablet

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

Intervention Type: DRUG

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%.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ilkos Therapeutic Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eberhard Rabe, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Dermatology University of Bonn

Locations

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

Foot and Ankle Clinic

Los Angeles, California, United States

Stanford Hospitals and Clinics

Redwood City, California, United States

Center for Clinical Research Inc.

San Francisco, California, United States

University of Miami Hospital Wound Center

Miami, Florida, United States

St. Luke's Intermountain Research Center

Boise, Idaho, United States

Podiatry 1st

Belleville, Illinois, United States

Advanced Foot & Ankle Center

Las Vegas, Nevada, United States

The Snyder Institute for Vascular Health and Research

Kittanning, Pennsylvania, United States

D&P Medical Group, LLC

Pittsburgh, Pennsylvania, United States

Serena Group Research Foundation

Pittsburgh, Pennsylvania, United States

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, , Argentina

Medizinische Universitaet Innsbruck Universitaetsklinik für Gefässchirurgie

Innsbruck, , Austria

VENEX Zentrum fuer minimal invasive Venentherapie

Vienna, , Austria

Medizinische Universitaet Wien AKH- Dermatologie

Vienna, , Austria

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, , Brazil

Alberta Health Services

Calgary, Alberta, Canada

Parkwood Institute

London, Ontario, Canada

Toronto Regional Dermatology & Wound Healing Clinic

Mississauga, Ontario, Canada

Ottawa Hospital Civic Campus

Ottawa, Ontario, Canada

Centrepoint Medical Center

Ottawa, Ontario, Canada

York Dermatology Center

Richmond Hill, Ontario, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

I. Dermatovenerologicka Klinika

Brno, , Czechia

MATMED s.r.o.

Hodonín, , Czechia

Nemocnice Jihlava Chirurgie A

Jihlava, , Czechia

Nemocnice Trebic Kozni oddeleni p.o.

Třebíč, , Czechia

Angiocor s.r.o.

Zlín, , Czechia

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Peterfy Sandor Utcai Korhaz

Budapest, , Hungary

Egyesitett Szent Istvan es Szent

Budapest, , Hungary

Bajcsy-Zsilinsky Korhaz

Budapest, , Hungary

Magyar Honvedseg Egeszsegugyi

Budapest, , Hungary

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum

Debrecen, , Hungary

Bacs-Kiskun Megyei Korhaz

Kecskemét, , Hungary

Josa Andras Oktatokorhaz

Nyíregyháza, , Hungary

Pesi Tudomanyegyetem Klnikai Kozpont

Pécs, , Hungary

Szegedi Tudomanyegyetem Borgyogyaszati es Allergologiai Klinica

Szeged, , Hungary

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

Padua, , 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 Marina, , Italy

Ospedale Belcolle - U.O Angiologia

Viterbo, , Italy

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, , Poland

ALIAN, s.r.o., Poliklinika ČK 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, , Slovakia

MEDIVASA, s.r.o.

Žilina, , Slovakia

Fundacion Hospital de Aviles

Avilés, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Consorci Sanitari de Terrassa - Hospital de Terrassa

Barcelona, , Spain

Hospital Universitario de Getafe

Getafe, , Spain

Hospital de la Cruz Roja de Madrid

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Complejo Asistencial Universitario

Salamanca, , Spain

Hospital de Manises

Valencia, , Spain

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CL2-42909-016

Identifier Type: -

Identifier Source: org_study_id