A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms
VITALISScE™
A Phase II, Randomised, Placebo-controlled, Double-blind, Parallel Group, Efficacy and Safety Study of at Least 48 Weeks of Oral BI 685509 Treatment in Adults With Progressive Systemic Sclerosis
2 other identifiers
interventional
214
36 countries
163
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2022
Typical duration for phase_2
163 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2022
CompletedFirst Posted
Study publicly available on registry
September 29, 2022
CompletedStudy Start
First participant enrolled
December 13, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 22, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2026
CompletedMarch 17, 2026
March 1, 2026
2.9 years
September 26, 2022
March 16, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks
48 weeks.
Secondary Outcomes (13)
Absolute change from baseline in Modified Rodnan Skin Score (mRSS) at Week 48 in study participants with diffuse cutaneous systemic sclerosis (dcSSc)
At baseline and at week 48.
Proportion of responders in study participants with diffuse cutaneous systemic sclerosis (dcSSc) based on the revised Composite Response Index in Systemic Sclerosis (CRISS) at Week 48
At baseline and at week 48.
Absolute change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48
At baseline and at week 48.
American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) score in study participants with diffuse cutaneous systemic sclerosis (dcSSc) at Week 48
At week 48.
Absolute change from baseline in forced vital capacity (FVC) (mL) at Week 48
At week 48.
- +8 more secondary outcomes
Study Arms (2)
Avenciguat (BI 685509)
EXPERIMENTALAvenciguat (BI 685509)
Placebo
PLACEBO COMPARATORPlacebo
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- Male or female patients aged ≥18 years at time of consent (or above legal age, e.g. United Kingdom (UK) ≥16 years).
- Patients must fulfill the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for Systemic sclerosis (SSc).
- 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.
- 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.
- 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
- 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.
- +5 more criteria
You may not qualify if:
- Any known form of pulmonary hypertension.
- Pulmonary disease with FVC \<50% of predicted. at screening.
- Other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren syndrome.
- Diffusing capacity for carbon monoxide (DLCO) (haemoglobin corrected) \<40% of predicted at screening.
- Any history of scleroderma renal crisis within the last 6 months.
- Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology (CKD-EPI) formula) or on dialysis at screening.
- Cirrhosis of any Child-Pugh class (A, B or C).
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (168)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Mayo Clinic
Scottsdale, Arizona, 85259, United States
Medvin Clinical Research-Covina-67001
Covina, California, 91722, United States
Southern California Scleroderma and Rheumatology Center
Inglewood, California, 90301, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
Medvin Clinical Research-Whittier-69033
Whittier, California, 90602, United States
Yale University School of Medicine
New Haven, Connecticut, 06519, United States
University of Florida
Gainesville, Florida, 32610, United States
Mayo Clinic - Florida
Jacksonville, Florida, 32224, United States
Iris Research and Development
Plantation, Florida, 33324, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Augusta University
Augusta, Georgia, 30912, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic, Rochester
Rochester, Minnesota, 55905, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
The University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
Centro de Investigaciones Metabolicas (CINME)-C.A.B.A-61553
C.a.b.a, 1056, Argentina
Hospital Britanico de Buenos Aires
CABA, 1280AEB, Argentina
STAT Research
CABA, C1023AAB, Argentina
Instituto de Investigación Clínica TyT
CABA, C1405BFN, Argentina
Psoriahue Medicina Interdisciplinaria S.R.L
CABA, C1425DKG, Argentina
Hospital Italiano de La Plata
La Plata, B1900AXI, Argentina
Centro de Investigaciones Medicas Mar del Plata
Mar del Plata, 7600, Argentina
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
St Vincent's Hospital Melbourne
Fitzroy, Victoria, 3065, Australia
Medical University of Graz State Hospital - University Hospital Graz
Graz, 8036, Austria
Ordensklinikum Linz GmbH
Linz, 4020, Austria
ULB Hopital Erasme
Brussels, 1070, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
UZ Leuven
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
SAPIENS - Instituto de Estudos e Pesquisa Clínica
Curitiba, 80440-210, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
São Bernardo do Campo, 09780-000, Brazil
Hospital do RIM - UNIFESP
São Paulo, 04023-062, Brazil
St. Paul's Hospital (Vancouver)
Vancouver, British Columbia, V1Y 1S1, Canada
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6, Canada
Mount Sinai Hospital (Toronto)
Toronto, Ontario, M5T 3L9, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 0A9, Canada
Centro Internacional de Estudios Clínicos (CIEC)
Comuna de Recoleta, 8420383, Chile
Clínica Dermacross S.A.
Vitacura, 7640881, Chile
Peking Union Medical College Hospital
Beijing, 100032, China
Peking University Third Hospital
Beijing, 100191, China
The First Affiliated Hospital Of Bengbu Medical College
Bengbu, 233004, China
The First Hospital of Jilin University
Changchun, 130021, China
West China Hospital, Sichuan University
Chengdu, 610041, China
Guangdong Provincial People's Hospital
Guangzhou, 510080, China
The third affiliated hospital of Sun Yat-Sen University
Guangzhou, 510630, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, 310009, China
Nanjing Drum Tower Hospital
Nanjing, 210008, China
The First Affiliated Hospital of Ningbo University
Ningbo, 315010, China
Huashan Hospital, Fudan University
Shanghai, 200040, China
The First Affiliated Hospital of Soochow University
Suzhou, 215006, China
Tianjin Medical University General Hospital
Tianjin, 30052, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, 325000, China
Wuhan Union Hospital
Wuhan, 430022, China
Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
Wuhan, 430030, China
Institute of Rheumathology Prague
Prague, 12800, Czechia
Medical Plus s.r.o., Rheumatology Outpatient Clinic
Uherské Hradiště, 686 01, Czechia
Aarhus University Hospital
Aarhus N, 8200, Denmark
Kuopio University Hospital
Kuopio, 70210, Finland
TYKS
Turku, 20521, Finland
HOP Annecy-Genevois
Epagny Metz-Tessy, 74370, France
HOP Hôtel-Dieu
Nantes, 44093, France
Hôpital Cochin
Paris, 75014, France
HOP Pontchaillou
Rennes, 35003, France
HOP Civil
Strasbourg, 67091, France
Hôpital Rangueil - CHU de Toulouse
Toulouse, 31059, France
HOP Brabois
Vandœuvre-lès-Nancy, 54500, France
Charité - Universitätsmedizin Berlin
Berlin, 10117, Germany
Universitätsklinikum Köln (AöR)
Cologne, 50937, Germany
Universitätsklinikum Erlangen
Erlangen, 91054, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Klinikum der Universität München AÖR
München, 80337, Germany
Westfälische Wilhelms-Universität Münster
Münster, 48149, Germany
General Hospital of Athens "Laiko"
Athens, 115 27, Greece
General Hospital of Athens "Laiko"
Athens, 11527, Greece
St John's Medical College
Bangalore, 560 034, India
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012, India
Sree Sudheendra Medical Mission
Kochi, 682018,, India
Post Graduate Institute of Medical Education and Research
Kolkata, 700020, India
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Maharashtra, 400053, India
Chopda Medicare and Research Centre Pvt Ltd
Maharashtra, 422005, India
All India Institute of Medical Sciences
New Delhi, 110029, India
Grant Medical Foundation, Ruby Hall Clinic
Pune, 411001, India
Krishna Institute of Medical Sciences
Secunderabad, 500003, India
Rambam Medical Center
Haifa, 3109601, Israel
Bnai Zion Medical Center, Haifa
Haifa, 3339419, Israel
Meir Medical Center
Kfar Saba, 4428164, Israel
Western Galilee Hospital
Nahariya, 2210001, Israel
The Chaim Sheba Medical Center Tel HaShomer
Ramat Gan, 5262000, Israel
Ospedali Riuniti di Ancona
Ancona, 60126, Italy
A.O. Spedali Civili di Brescia
Brescia, 25123, Italy
Azienda Ospedaliero Universitaria Careggi
Florence, 50139, Italy
Azienda Ospedaliera San Martino
Genova, 16132, Italy
Istituto Ortopedico G.Pini
Milan, 20122, Italy
Ospedale San Raffaele S.r.l.
Milan, 20132, Italy
Azienda Ospedaliero-Universitaria di Modena
Modena, 41124, Italy
Fondazione Policlinico Universitario Campus Bio-medico
Roma, 00128, Italy
AOU Policlinico Umberto I
Roma, 00161, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00195, Italy
Japan Community Healthcare Organization Chukyo Hospital
Aichi, Nagoya, 457-8510, Japan
Hospital of the University of Occupational and Environmental Health
Fukuoka, Kitakyushu, 807-8555, Japan
Hokkaido University Hospital
Hokkaido, Sapporo, 060-8648, Japan
Kanazawa University Hospital
Ishikawa, Kanazawa, 920-8641, Japan
Kyoto University Hospital
Kyoto, Kyoto, 606-8507, Japan
The University of Osaka Hospital
Osaka, Suita, 565-0871, Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603, Japan
Wakayama Medical University Hospital
Wakayama, Wakayama, 641-8509, Japan
University of Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Hospital Selayang
Kuala Selangor, 68100, Malaysia
Investigacion y Biomedicina de Chihuahua S.C.
Chihuahua City, 31020, Mexico
Centro Integral en Reumatologia, SA. de CV.
Guadalajara, 44160, Mexico
Medical Care & Research SA de CV
Mérida, 97070, Mexico
Oaxaca Site Management Organization, S.C.
Oaxaca City, 68000, Mexico
Leids Universitair Medisch Centrum (LUMC)
Leiden, 2333 ZA, Netherlands
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA, Netherlands
Waikato Hospital
Hamilton, 3204, New Zealand
Oslo Universitetssykehus HF, Rikshospitalet
Oslo, N-0372, Norway
Manila Doctors Hospital
Manila, 1000, Philippines
St. Luke's Medical Center-Quezon-59457
Quezon City, 1112, Philippines
Malopolska Clinical Research
Krakow, 30-002, Poland
Medical Center Hetmanska
Poznan, 60-218, Poland
National Medical Institute MSWiA
Warsaw, 02-507, Poland
Prof Eleonora Reicher Memorial Institute of Rheumatology
Warsaw, 02-637, Poland
Military Medical Institute- National Research Institute
Warsaw, 04 141, Poland
ULS de Almada -Seixal, E. P. E. - Hospital Garcia de Orta
Almada, 2801-951, Portugal
Bacau County Hospital
Bacau, 600114, Romania
C.M.D.T.A. NEOMED, Brasov
Brasov, 500283, Romania
Dr. Ion Cantacuzino Clinical Hospital
Bucharest, 020475, Romania
S.C. Policlinica CCBR S.R.L.
Bucharest, 030463, Romania
St. Mary's Clinical Hospital
Bucharest, 11172, Romania
Cluj Napoca Clinical County Hospital
Cluj-Napoca, 400006, Romania
Aqua Clinic (AquaMed Consulting SRL- juridic)
Constanța, 900622, Romania
SC Medaudio Optica SRL
Râmnicu Vâlcea, 240762, Romania
Singapore General Hospital
Singapore, 169608, Singapore
Tan Tock Seng Hospital
Singapore, 308433, Singapore
Seoul National University Hospital
Seoul, 03080, South Korea
Soonchunhyang University Hospital Seoul
Seoul, 04401, South Korea
Hanyang University Medical Center
Seoul, 04763, South Korea
Hospital Santa Creu i Sant Pau
Barcelona, 08026, Spain
Hospital Universitari Vall D Hebron
Barcelona, 08035, Spain
Hospital Universitario Ramon Y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Clínico de Santiago
Santiago de Compostela, 15706, Spain
Hospital Dr. Peset
Valencia, 46017, Spain
Clinical Rheumatology Research Center Sahlgrenska
Gothenburg, 413 45, Sweden
Kantonsspital St.Gallen
Sankt Gallen, 9007, Switzerland
University Hospital Zurich
Zurich, 8091, Switzerland
China Medical University Hospital
Taichung, 40447, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Maharaj Nakom Chiangmai Hospital
Chiang Mai, 50200, Thailand
Songklanagarind Hospital
Hat Yai, 90110, Thailand
Srinagarind Hospital
Muang, 40002, Thailand
Ramathibodi Hospital
Ratchathewi, 10400, Thailand
Akdeniz Universitesi Tip Fakultesi -ANTALYA-33606
Antalya, 07070, Turkey (Türkiye)
Firat University Hospital
Elâzığ, 23200, Turkey (Türkiye)
Chapel Allerton Hospital
Leeds, LS7 4SA, United Kingdom
Aintree University Hospital
Liverpool, L9 7AL, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
Salford Royal
Salford, M6 8HD, United Kingdom
Related Publications (2)
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.
PMID: 39985455DERIVEDKhanna 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;10(1):27-35. doi: 10.1177/23971983241291923. eCollection 2025 Feb.
PMID: 39544899DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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).
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2022
First Posted
September 29, 2022
Study Start
December 13, 2022
Primary Completion
October 22, 2025
Study Completion
January 30, 2026
Last Updated
March 17, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
- Access Criteria
- For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.