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

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.

Study Overview

• Status: Completed
• Conditions: Scleroderma, Systemic
• Intervention / Treatment: Drug: Placebo; Drug: Avenciguat (BI 685509)

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • C.a.b.a, Argentina, 1056
    • Centro de Investigaciones Metabolicas (CINME)-C.A.B.A-61553
  • CABA, Argentina, 1280AEB
    • Hospital Británico de Buenos Aires
  • CABA, Argentina, C1023AAB
    • Stat Research
  • CABA, Argentina, C1405BFN
    • Instituto de Investigación Clínica TyT
  • CABA, Argentina, C1425DKG
    • Psoriahue Medicina Interdisciplinaria S.R.L
  • La Plata, Argentina, B1900AXI
    • Hospital Italiano de La Plata
  • Mar del Plata, Argentina, 7600
    • Centro de Investigaciones Medicas Mar del Plata
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
• Austria
  • Graz, Austria, 8036
    • Medical University of Graz State Hospital - University Hospital Graz
  • Linz, Austria, 4020
    • Ordensklinikum Linz GmbH
• Belgium
  • Brussels, Belgium, 1070
    • ULB Hopital Erasme
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège
• Brazil
  • Curitiba, Brazil, 80440-210
    • SAPIENS - Instituto de Estudos e Pesquisa Clínica
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clínicas de Porto Alegre
  • São Bernardo do Campo, Brazil, 09780-000
    • CEMEC - Centro Multidisciplinar de Estudos Clínicos
  • São Paulo, Brazil, 04023-062
    • Hospital do RIM - UNIFESP
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V1Y 1S1
      • St. Paul's Hospital (Vancouver)
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Toronto, Ontario, Canada, M5T 3L9
      • Mount Sinai Hospital (Toronto)
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• Chile
  • Comuna de Recoleta, Chile, 8420383
    • Centro Internacional de Estudios Clínicos (CIEC)
  • Vitacura, Chile, 7640881
    • Clinica Dermacross S.A.
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100032
    • Peking Union Medical College Hospital
  • Bengbu, China, 233004
    • The First Affiliated Hospital Of Bengbu Medical College
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Guangzhou, China, 510080
    • Guangdong Provincial People's Hospital
  • Guangzhou, China, 510630
    • The third affiliated hospital of Sun Yat-Sen University
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital Zhejiang University School of Medicine
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
  • Ningbo, China, 315010
    • The First Affiliated Hospital of Ningbo University
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Suzhou, China, 215006
    • The First Affiliated Hospital of Soochow University
  • Tianjin, China, 30052
    • Tianjin Medical University General Hospital
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430022
    • Wuhan Union Hospital
  • Wuhan, China, 430030
    • Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
• Czechia
  • Prague, Czechia, 12800
    • Institute of Rheumathology Prague
  • Uherské Hradiště, Czechia, 686 01
    • Medical Plus s.r.o., Rheumatology Outpatient Clinic
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
• Finland
  • Kuopio, Finland, 70210
    • Kuopio University Hospital
  • Turku, Finland, 20521
    • TYKS
• France
  • Epagny Metz-Tessy, France, 74370
    • HOP Annecy-Genevois
  • Nantes, France, 44093
    • HOP Hôtel-Dieu
  • Paris, France, 75014
    • Hôpital Cochin
  • Rennes, France, 35003
    • HOP Pontchaillou
  • Strasbourg, France, 67091
    • HOP Civil
  • Toulouse, France, 31059
    • Hôpital Rangueil - CHU de Toulouse
  • Vandœuvre-lès-Nancy, France, 54500
    • HOP Brabois
• Germany
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin
  • Cologne, Germany, 50937
    • Universitätsklinikum Köln (AöR)
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
  • München, Germany, 80337
    • Klinikum der Universität München AÖR
  • Münster, Germany, 48149
    • Westfälische Wilhelms-Universität Münster
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Laiko"
  • Athens, Greece, 115 27
    • General Hospital of Athens "Laiko"
• India
  • Bangalore, India, 560 034
    • St John's Medical College
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education and Research
  • Kochi, India, 682018,
    • Sree Sudheendra Medical Mission
  • Kolkata, India, 700020
    • Post Graduate Institute of Medical Education and Research
  • Maharashtra, India, 422005
    • Chopda Medicare and Research Centre Pvt Ltd
  • Maharashtra, India, 400053
    • Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Pune, India, 411001
    • Grant Medical Foundation, Ruby Hall Clinic
  • Secunderabad, India, 500003
    • Krishna Institute of Medical Sciences
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Haifa, Israel, 3339419
    • Bnai Zion Medical Center, Haifa
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Nahariya, Israel, 2210001
    • Western Galilee Hospital
  • Ramat Gan, Israel, 5262000
    • The Chaim Sheba Medical Center Tel HaShomer
• Italy
  • Ancona, Italy, 60126
    • Ospedali Riuniti di Ancona
  • Brescia, Italy, 25123
    • A.O. Spedali Civili di Brescia
  • Florence, Italy, 50139
    • Azienda Ospedaliero Universitaria Careggi
  • Genova, Italy, 16132
    • Azienda Ospedaliera San Martino
  • Milan, Italy, 20132
    • Ospedale San Raffaele S.r.l.
  • Milan, Italy, 20122
    • Istituto Ortopedico G.Pini
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena
  • Roma, Italy, 00161
    • AOU Policlinico Umberto I
  • Roma, Italy, 00128
    • Fondazione Policlinico Universitario Campus Bio-medico
  • Roma, Italy, 00195
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Japan
  • Aichi, Nagoya, Japan, 457-8510
    • Japan Community Healthcare Organization Chukyo Hospital
  • Fukuoka, Kitakyushu, Japan, 807-8555
    • Hospital of the University of Occupational and Environmental Health
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Ishikawa, Kanazawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kyoto, Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Osaka, Suita, Japan, 565-0871
    • The University of Osaka Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8603
    • Nippon Medical School Hospital
  • Wakayama, Wakayama, Japan, 641-8509
    • Wakayama Medical University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
  • Kuala Selangor, Malaysia, 68100
    • Hospital Selayang
• Mexico
  • Chihuahua City, Mexico, 31020
    • Investigacion y Biomedicina de Chihuahua S.C.
  • Guadalajara, Mexico, 44160
    • Centro Integral en Reumatologia, SA. de CV.
  • Mérida, Mexico, 97070
    • Medical Care & Research SA de CV
  • Oaxaca City, Mexico, 68000
    • Oaxaca Site Management Organization, S.C.
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Universitair Medisch Centrum
• New Zealand
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
• Norway
  • Oslo, Norway, N-0372
    • Oslo Universitetssykehus HF, Rikshospitalet
• Philippines
  • Manila, Philippines, 1000
    • Manila Doctors Hospital
  • Quezon City, Philippines, 1112
    • St. Luke's Medical Center-Quezon-59457
• Poland
  • Krakow, Poland, 30-002
    • Malopolska Clinical Research
  • Poznan, Poland, 60-218
    • Medical Center Hetmanska
  • Warsaw, Poland, 02-507
    • National Medical Institute MSWiA
  • Warsaw, Poland, 04 141
    • Military Medical Institute- National Research Institute
  • Warsaw, Poland, 02-637
    • Prof Eleonora Reicher Memorial Institute of Rheumatology
• Portugal
  • Almada, Portugal, 2801-951
    • ULS de Almada -Seixal, E. P. E. - Hospital Garcia de Orta
• Romania
  • Bacau, Romania, 600114
    • Bacau County Hospital
  • Brasov, Romania, 500283
    • C.M.D.T.A. NEOMED, Brasov
  • Bucharest, Romania, 030463
    • S.C. Policlinica CCBR S.R.L.
  • Bucharest, Romania, 11172
    • St. Mary's Clinical Hospital
  • Bucharest, Romania, 020475
    • Dr. Ion Cantacuzino Clinical Hospital
  • Cluj-Napoca, Romania, 400006
    • Cluj Napoca Clinical County Hospital
  • Constanța, Romania, 900622
    • Aqua Clinic (AquaMed Consulting SRL- juridic)
  • Râmnicu Vâlcea, Romania, 240762
    • SC Medaudio Optica SRL
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 04401
    • Soonchunhyang University Hospital Seoul
  • Seoul, South Korea, 04763
    • Hanyang University Medical Center
• Spain
  • Barcelona, Spain, 08026
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico de Santiago
  • Valencia, Spain, 46017
    • Hospital Dr. Peset
• Sweden
  • Gothenburg, Sweden, 413 45
    • Clinical Rheumatology Research Center Sahlgrenska
• Switzerland
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St.Gallen
  • Zurich, Switzerland, 8091
    • University Hospital Zurich
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• Thailand
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakom Chiangmai Hospital
  • Hat Yai, Thailand, 90110
    • Songklanagarind Hospital
  • Muang, Thailand, 40002
    • Srinagarind Hospital
  • Ratchathewi, Thailand, 10400
    • Ramathibodi Hospital
• Turkey (Türkiye)
  • Antalya, Turkey (Türkiye), 07070
    • Akdeniz Universitesi Tip Fakultesi -ANTALYA-33606
  • Elâzığ, Turkey (Türkiye), 23200
    • Firat University Hospital
• United Kingdom
  • Leeds, United Kingdom, LS7 4SA
    • Chapel Allerton Hospital
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital
  • London, United Kingdom, Nw3 2QG
    • Royal Free Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Covina, California, United States, 91722
      • Medvin Clinical Research-Covina-67001
    • Inglewood, California, United States, 90301
      • Southern California Scleroderma and Rheumatology Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Whittier, California, United States, 90602
      • Medvin Clinical Research-Whittier-69033
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Florida
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
   • If none of the four criteria above are met, the patient can be entered if the diagnosis of Interstitial lung disease (ILD) has been confirmed Further inclusion criteria apply.

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.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Avenciguat (BI 685509)	Drug: Avenciguat (BI 685509); Avenciguat (BI 685509)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks	48 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48	HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area.	At baseline and at week 48.
Absolute change from baseline in forced vital capacity (FVC) (% predicted) at Week 48		At baseline and at week 48.
Absolute change from baseline in the Patient Global Assesment (PGA) Visual Analog Scale (VAS) score at Week 48	The PGA is a self-assessment on the patient's overall health in the prior 1 week using a 0-10 ordinal scale, with a higher score indicating a worse outcome.	At baseline and at week 48.
Absolute change from baseline in the Clinician Global Assessment (CGA) Visual Analog Scale (VAS) score at Week 48	Clinician assessment (CGA) on the patient's overall health in the prior 1 week using a 0-10 ordinal scale, with a higher score indicating a worst outcome.	At baseline and at week 48.
Composite measure of Raynaud's phenomenon (RP) activity at Week 48		Week 48.
Absolute change from baseline in Digital ulcer (DU) net burden at Week 48		At baseline and at week 48.
Time to treatment failure	Time to treatment failure, defined as the time to one of the following events (whichever occurs first) occurring over the 48-week and extended treatment period: death,; absolute decline in percent-predicted forced vital capacity (FVC) ≥10% relative to baseline,; ≥25% increase in Modified Rodnan Skin Score (mRSS) and an increase in mRSS of >5 points,; initiation or dose change of immunomodulating/immunosuppressive therapy for clinically significant deterioration of Diffuse cutaneous systemic sclerosis (dcSSc)	48 weeks.
Absolute change from baseline in forced vital capacity (FVC) (mL) at Week 48		At week 48.
Absolute change from baseline in Modified Rodnan Skin Score (mRSS) at Week 48 in study participants with diffuse cutaneous systemic sclerosis (dcSSc)	To measure mRSS, skin thickness of the patient is rated by palpation using a scale of 0-3, with 0 = normal skin; 1= mild thickness; 2= moderate thickness and 3=severe thickness with an inability to pinch the skin into a fold (worst outcome).	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	Revised Composite Response Index in Systemic Sclerosis (CRISS) at Week 48 (Achievement of ≥ 20% improvement from baseline to week 48 in at least 3 of the 5 core set measures, except ≥ 5% in Forced Vital Capacity (FVC) percent predicted). The CRISS is a two-step composite index which includes in Step 2 the mRSS, FVC percent predicted, HAQ-DI, patient's global assessment and clinicians's global assessment. Step 1 in the ACR-CRISS version consists of the absence of significant worsening of interstitial lung disease, a new scleroderma renal crisis, left ventricular failure or pulmonary arterial hypertension. The revised version proposes that the absence of significant gastrointestinal dysmotility requiring parenteral or enteral nutrition and significant digital ischaemia requiring hospitalisation, gangrene or amputation are added to Step 1. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A higher score indicates greater improvement.	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	The CRISS is a two-step composite index which includes in Step 2 the Modified Rodnan Skin Score (mRSS), FVC percent predicted, Health Assessment Questionnaire - Disability Index (HAQ-DI), patient's global assessment and clinicians's global assessment. Step 1 in the ACR-CRISS version consists of the absence of significant worsening of interstitial lung disease, a new scleroderma renal crisis, left ventricular failure or pulmonary arterial hypertension. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A higher score indicates greater improvement.	At week 48.
Time to Modified Rodnan Skin Score (mRSS) progression (≥25% increase in mRSS and an increase in mRSS of >5 points) in study participants with diffuse cutaneous systemic sclerosis (dcSSc)		48 weeks.
Proportion of study participants with diffuse cutaneous systemic sclerosis (dcSSc) with Modified Rodnan Skin Score (mRSS) progression (25% increase in mRSS and an increase in mRSS of >5 points)		48 weeks.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.
• 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;10(1):27-35. doi: 10.1177/23971983241291923. eCollection 2025 Feb.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): October 22, 2025
• Study Completion (Actual): January 30, 2026

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 1366-0031; 2022-500332-11-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No