A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms

NCT ID: NCT05559580

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-13

Study Completion Date

2026-02-27

Brief Summary

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This study is open to adults aged 18 and older or above legal age who have systemic sclerosis. People can participate if they have a specific subtype called diffuse cutaneous systemic sclerosis. People with another subtype called limited cutaneous systemic sclerosis can also participate if they are anti Scl-70 antibody positive. Systemic sclerosis is also called scleroderma.

The purpose of this study is to find out whether a medicine called Avenciguat (BI 685509) helps people with scleroderma who have symptoms due to lung fibrosis or vascular problems.

Participants are put into 2 groups by chance. One group takes Avenciguat (BI 685509) tablets 3 times a day and the other group takes placebo tablets 3 times a day. Placebo tablets look like BI 685509 tablets but do not contain any medicine. Participants take the tablets for at least 11 months. Afterwards, participants can continue to take the tablets until the last participant has completed the 11-months treatment period. This means that the time in the study and duration of treatment is different for each participant, depending on when they start the study. At the beginning of the study, participants visit the study site every 2 weeks. The time between the visits to the study site gets longer over the course of the study. After the 11-months treatment period, participants visit the study site every 3 months.

During the study, participants regularly do lung function tests. The results are compared between the 2 groups to see whether the treatment works. The participants also regularly fill in questionnaires about their scleroderma symptoms. The doctors regularly check participants' skin condition and general health and take note of any unwanted effects.

Detailed Description

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Conditions

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Scleroderma, Systemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Patients, investigators, central reviewers, and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial will remain blinded regarding the randomised treatment assignments until the database is declared ready for analysis according to the sponsor's Standard Operating Procedures (SOPs).

Study Groups

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Avenciguat (BI 685509)

Avenciguat (BI 685509)

Group Type EXPERIMENTAL

Avenciguat (BI 685509)

Intervention Type DRUG

Avenciguat (BI 685509)

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

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Avenciguat (BI 685509)

Avenciguat (BI 685509)

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
2. Male or female patients aged ≥18 years at time of consent (or above legal age, e.g. United Kingdom (UK) ≥16 years).
3. Patients must fulfill the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for Systemic sclerosis (SSc).
4. Patients must be diagnosed with limited or with diffuse cutaneous SSc as defined by LeRoy et al. (R17 0149). Patients diagnosed with limited cutaneous SSc may be included if they are anti Scl-70 antibody positive.
5. Diffuse cutaneous SSc disease onset (defined by first non-RP symptom) in patients with diffuse cutaneous SSc must be within 7 years of Visit 1. Limited cutaneous SSc onset must be within 2 years of Visit 1.
6. Evidence of active disease, defined as having at least one of the following:

* New onset of SSc within the last 2 years of Visit 1 OR
* New skin involvement or worsening of two new body areas within 6 months of Visit 1 (out of the possible 17 body areas defined by Modified Rodnan Skin Score (mRSS) assessment, documented in clinical files) OR
* New involvement or worsening of one new body area if either chest or abdomen within 6 months of Visit 1 OR
* Worsening of skin thickening (e.g. ≥2 mRSS points) within 6 months of Visit 1 OR
* ≥1 tendon friction rub
7. Elevated biomarkers on Visit 1 (screening) defined as at least one of the following:

* C-reactive protein (CRP) ≥6 mg/L (≥0.6 mg/dL), OR
* Erythrocyte sedimentation rate (ESR) ≥28 mm/h, OR
* Krebs von den Lungen 6 (KL-6) ≥1000 U/mL If none of the three criteria are met or respective test results should not be available, the patient can be entered if the modified Disease Activity Index (mDAI) is ≥ 2.5.
8. Evidence of significant vasculopathy, defined as:

* Active Digital ulcer (DU(s)) on Visit 1 OR
* Documented history of DU(s), OR
* Previous treatment of RP with prostacyclin analogues or ≥ 1 other medications, including calcium channel blockers, nitrates,, NO donors in any form, including topical; phosphodiesterase 5 (PDE5) inhibitors (e.g. sildenafil, tadalafil, vardenafil); nonspecific PDE5 inhibitors (theophylline, dipyridamole) OR
* RP with elevated CRP ≥6 mg/L

Exclusion Criteria

1. Any known form of pulmonary hypertension.
2. Pulmonary disease with FVC \<50% of predicted. at screening.
3. Other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren syndrome.
4. Diffusing capacity for carbon monoxide (DLCO) (haemoglobin corrected) \<40% of predicted at screening.
5. Any history of scleroderma renal crisis within the last 6 months.
6. Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology (CKD-EPI) formula) or on dialysis at screening.
7. Cirrhosis of any Child-Pugh class (A, B or C).
8. Cholestasis at present, or Alkaline phosphatase (ALP) \> 4 x Upper limit of normal (ULN), or ALP \> 2 x ULN and Gamma-glutamyl transferase (GGT) \> 3 x ULN at Screening.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

Medvin Clinical Research-Covina-67001

Covina, California, United States

Site Status

Southern California Scleroderma and Rheumatology Center

Inglewood, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

Medvin Clinical Research-Whittier-69033

Whittier, California, United States

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Yale University School of Medicine

New Haven, Connecticut, United States

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University of Florida

Gainesville, Florida, United States

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Mayo Clinic - Florida

Jacksonville, Florida, United States

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Iris Research and Development

Plantation, Florida, United States

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The Emory Clinic

Atlanta, Georgia, United States

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Augusta University

Augusta, Georgia, United States

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University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

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Tufts Medical Center

Boston, Massachusetts, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

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University of Michigan Health System

Ann Arbor, Michigan, United States

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Mayo Clinic, Rochester

Rochester, Minnesota, United States

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University of Cincinnati Medical Center

Cincinnati, Ohio, United States

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Thomas Jefferson University

Philadelphia, Pennsylvania, United States

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The University of Texas Health Science Center at Houston

Houston, Texas, United States

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Centro de Investigaciones Metabolicas (CINME)-C.A.B.A-61553

C.a.b.a, , Argentina

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Hospital Britanico de Buenos Aires

CABA, , Argentina

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STAT Research

CABA, , Argentina

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Instituto de Investigación Clínica TyT

CABA, , Argentina

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Psoriahue Medicina Interdisciplinaria S.R.L

CABA, , Argentina

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Hospital Italiano de La Plata

La Plata, , Argentina

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Centro de Investigaciones Medicas Mar del Plata

Mar del Plata, , Argentina

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Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

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Liverpool Hospital

Liverpool, New South Wales, Australia

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Westmead Hospital

Westmead, New South Wales, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

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St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

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Medical University of Graz State Hospital - University Hospital Graz

Graz, , Austria

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Ordensklinikum Linz GmbH

Linz, , Austria

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ULB Hopital Erasme

Brussels, , Belgium

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Universitair Ziekenhuis Gent

Ghent, , Belgium

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UZ Leuven

Leuven, , Belgium

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Centre Hospitalier Universitaire de Liège

Liège, , Belgium

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Edumed - Educacao e Saude SA

Curitiba, , Brazil

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Hospital de Clínicas de Porto Alegre

Porto Alegre, , Brazil

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CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, , Brazil

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Hospital do RIM - UNIFESP

São Paulo, , Brazil

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St. Paul's Hospital (Vancouver)

Vancouver, British Columbia, Canada

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St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

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Mount Sinai Hospital-Toronto-18157

Toronto, Ontario, Canada

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Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

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Centro Internacional de Estudios Clínicos (CIEC)

Comuna de Recoleta, , Chile

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Clínica Dermacross S.A.

Vitacura, , Chile

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Peking Union Medical College Hospital

Beijing, , China

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Peking University Third Hospital

Beijing, , China

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The First Affiliated Hospital Of Bengbu Medical College

Bengbu, , China

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The First Hospital of Jilin University

Changchun, , China

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West China Hospital of Sichuan University

Chengdu, , China

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Guangdong Provincial People's Hospital

Guangzhou, , China

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The third affiliated hospital of Sun Yat-Sen University

Guangzhou, , China

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The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, , China

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Nanjing Drum Tower Hospital

Nanjing, , China

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The First Affiliated Hospital of Ningbo University

Ningbo, , China

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Huashan Hospital, Fudan University

Shanghai, , China

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The First Affiliated Hospital of Soochow University

Suzhou, , China

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Tianjin Medical University General Hospital

Tianjin, , China

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The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, , China

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Wuhan Union Hospital

Wuhan, , China

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Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T

Wuhan, , China

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Institute of Rheumathology Prague

Prague, , Czechia

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Medical Plus s.r.o., Rheumatology Outpatient Clinic

Uherské Hradiště, , Czechia

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Aarhus University Hospital

Aarhus N, , Denmark

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Kuopio University Hospital

Kuopio, , Finland

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TYKS

Turku, , Finland

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HOP Annecy-Genevois

Epagny Metz-Tessy, , France

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HOP Hôtel-Dieu

Nantes, , France

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Hôpital Cochin

Paris, , France

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HOP Pontchaillou

Rennes, , France

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HOP Civil

Strasbourg, , France

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HOP Rangueil

Toulouse, , France

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HOP Brabois

Vandœuvre-lès-Nancy, , France

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Charite Universitätsmedizin Berlin KöR

Berlin, , Germany

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Universitätsklinikum Köln (AöR)

Cologne, , Germany

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Universitätsklinikum Erlangen

Erlangen, , Germany

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Universitätsklinikum Heidelberg

Heidelberg, , Germany

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Klinikum der Universität München AÖR

München, , Germany

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Westfälische Wilhelms-Universität Münster

Münster, , Germany

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General Hospital of Athens "Laiko"

Athens, , Greece

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General Hospital of Athens "Laiko"

Athens, , Greece

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St John's Medical College

Bangalore, , India

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Post Graduate Institute of Medical Education and Research

Chandigarh, , India

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Sree Sudheendra Medical Mission

Kochi, , India

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Post Graduate Institute of Medical Education and Research

Kolkata, , India

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Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute

Maharashtra, , India

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Chopda Medicare and Research Centre Pvt Ltd

Maharashtra, , India

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All India Institute of Medical Sciences

New Delhi, , India

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Grant Medical Foundation, Ruby Hall Clinic

Pune, , India

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Krishna Institute of Medical Sciences

Secunderabad, , India

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Rambam Medical Center

Haifa, , Israel

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Bnai Zion Medical Center, Haifa

Haifa, , Israel

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Meir Medical Center

Kfar Saba, , Israel

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Western Galilee Hospital

Nahariya, , Israel

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The Chaim Sheba Medical Center Tel HaShomer

Ramat Gan, , Israel

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Ospedali Riuniti di Ancona

Ancona, , Italy

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A.O. Spedali Civili di Brescia

Brescia, , Italy

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Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

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Azienda Ospedaliera San Martino

Genova, , Italy

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Istituto Ortopedico G.Pini

Milan, , Italy

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Ospedale San Raffaele S.r.l.

Milan, , Italy

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Azienda Ospedaliera Policlinico di Modena

Modena, , Italy

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Fondazione Policlinico Universitario Campus Bio-medico

Roma, , Italy

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AOU Policlinico Umberto I

Roma, , Italy

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Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, , Italy

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Japan Community Healthcare Organization Chukyo Hospital

Aichi, Nagoya, , Japan

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Hospital of the University of Occupational and Environmental Health

Fukuoka, Kitakyushu, , Japan

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Hokkaido University Hospital

Hokkaido, Sapporo, , Japan

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Kanazawa University Hospital

Ishikawa, Kanazawa, , Japan

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Kyoto University Hospital

Kyoto, Kyoto, , Japan

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The University of Osaka Hospital

Osaka, Suita, , Japan

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Nippon Medical School Hospital

Tokyo, Bunkyo-ku, , Japan

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Wakayama Medical University Hospital

Wakayama, Wakayama, , Japan

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University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

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Hospital Selayang

Kuala Selangor, , Malaysia

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Investigacion y Biomedicina de Chihuahua S.C.

Chihuahua City, , Mexico

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Centro Integral en Reumatologia, SA. de CV.

Guadalajara, , Mexico

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Medical Care & Research SA de CV

Mérida, , Mexico

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Oaxaca Site Management Organization, S.C.

Oaxaca City, , Mexico

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Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

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Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

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Waikato Hospital

Hamilton, , New Zealand

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Oslo Universitetssykehus HF, Rikshospitalet

Oslo, , Norway

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Manila Doctors Hospital

Manila, , Philippines

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St. Luke's Medical Center-Quezon-59457

Quezon City, , Philippines

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Malopolska Clinical Research

Krakow, , Poland

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Medical Center Hetmanska

Poznan, , Poland

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National Medical Institute MSWiA

Warsaw, , Poland

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Prof Eleonora Reicher Memorial Institute of Rheumatology

Warsaw, , Poland

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Military Medical Institute- National Research Institute

Warsaw, , Poland

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ULS de Almada -Seixal, E. P. E. - Hospital Garcia de Orta

Almada, , Portugal

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Bacau County Hospital

Bacau, , Romania

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C.M.D.T.A. NEOMED, Brasov

Brasov, , Romania

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Dr. Ion Cantacuzino Clinical Hospital

Bucharest, , Romania

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S.C. Policlinica CCBR S.R.L.

Bucharest, , Romania

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St. Mary's Clinical Hospital

Bucharest, , Romania

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Cluj Napoca Clinical County Hospital

Cluj-Napoca, , Romania

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Aqua Clinic (AquaMed Consulting SRL- juridic)

Constanța, , Romania

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SC Medaudio Optica SRL

Râmnicu Vâlcea, , Romania

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Singapore General Hospital

Singapore, , Singapore

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Tan Tock Seng Hospital

Singapore, , Singapore

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Seoul National University Hospital

Seoul, , South Korea

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Soonchunhyang University Hospital Seoul

Seoul, , South Korea

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Hanyang University Medical Center

Seoul, , South Korea

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Hospital Santa Creu i Sant Pau

Barcelona, , Spain

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Hospital Universitari Vall D Hebron

Barcelona, , Spain

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Hospital Universitario Ramon Y Cajal

Madrid, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Clínico de Santiago

Santiago de Compostela, , Spain

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Hospital Dr. Peset

Valencia, , Spain

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Clinical Rheumatology Research Center Sahlgrenska

Gothenburg, , Sweden

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Kantonsspital St.Gallen

Sankt Gallen, , Switzerland

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University Hospital Zurich

Zurich, , Switzerland

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National Taiwan University Hospital

Taipei, , Taiwan

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Maharaj Nakom Chiangmai Hospital

Chiang Mai, , Thailand

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Songklanagarind Hospital

Hat Yai, , Thailand

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Srinagarind Hospital

Muang, , Thailand

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Ramathibodi Hospital

Ratchathewi, , Thailand

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Akdeniz Universitesi Tip Fakultesi -ANTALYA-33606

Antalya, , Turkey (Türkiye)

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Firat University Hospital

Elâzığ, , Turkey (Türkiye)

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Chapel Allerton Hospital

Leeds, , United Kingdom

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Aintree University Hospital

Liverpool, , United Kingdom

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Royal Free Hospital

London, , United Kingdom

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Salford Royal

Salford, , United Kingdom

Site Status

Countries

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Ireland United States Argentina Australia Austria Belgium Brazil Canada Chile China Czechia Denmark Finland France Germany Greece India Israel Italy Japan Malaysia Mexico Netherlands New Zealand Norway Philippines Poland Portugal Romania Singapore South Korea Spain Sweden Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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Kaufman J, Nabozny G, Tran-Manh C, Liebel C, Zhou X, Daley LA, Wang CT, Ebenezer DL, Delic D, Wohnhaas CT, Trinh-Minh T, Distler JHW. Avenciguat: a novel soluble guanylate cyclase activator that affects multiple cell types to inhibit IFN-1 signalling and fibrosis. Rheumatology (Oxford). 2025 Aug 1;64(8):4738-4743. doi: 10.1093/rheumatology/keaf109.

Reference Type DERIVED
PMID: 39985455 (View on PubMed)

Khanna D, de Vries-Bouwstra J, Hoffmann-Vold AM, Kuwana M, Low AHL, Proudman S, Flack M, Kukreja A, Fagan N, Distler O. A Phase II study of avenciguat, a novel soluble guanylate cyclase activator, in patients with systemic sclerosis: Study design and rationale of the VITALISScE study. J Scleroderma Relat Disord. 2024 Nov 7:23971983241291923. doi: 10.1177/23971983241291923. Online ahead of print.

Reference Type DERIVED
PMID: 39544899 (View on PubMed)

Related Links

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Other Identifiers

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2022-500332-11-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

1366-0031

Identifier Type: -

Identifier Source: org_study_id