A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms
- Conditions
- Scleroderma, Systemic
- Interventions
- Drug: Avenciguat (BI 685509)Drug: Placebo
- Registration Number
- NCT05559580
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 188
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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.
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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.
-
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.
- 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.
Further exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Avenciguat (BI 685509) Avenciguat (BI 685509) Avenciguat (BI 685509) Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks 48 weeks.
- Secondary Outcome Measures
Name Time Method 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. 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.
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) At baseline and at week 48. 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).
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. 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.
Absolute change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48 At baseline and 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.
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 At baseline and 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.
Absolute change from baseline in the Clinician Global Assessment (CGA) Visual Analog Scale (VAS) score at Week 48 At baseline and 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.
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 48 weeks. 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)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.
Trial Locations
- Locations (165)
Nippon Medical School Hospital
🇯🇵Tokyo, Bunkyo-ku, Japan
St. Mary's Clinical Hospital
🇷🇴Bucharest, Romania
Dr. Ion Cantacuzino Clinical Hospital, Bucharest
🇷🇴Bucharest, Romania
S.C. Policlinica CCBR S.R.L.
🇷🇴Bucharest, Romania
Cluj Napoca Clinical County Hospital
🇷🇴Cluj-Napoca, Romania
Azienda Ospedaliera Policlinico di Modena
🇮🇹Modena, Italy
Università degli Studi Campus Bio-Medico
🇮🇹Roma, Italy
AOU Policlinico Umberto I
🇮🇹Roma, Italy
Poli Univ A. Gemelli
🇮🇹Roma, Italy
Japan Community Healthcare Organization Chukyo Hospital
🇯🇵Aichi, Nagoya, Japan
Hospital of the University of Occupational and Environmental Health
🇯🇵Fukuoka, Kitakyushu, Japan
Gunma University Hospital
🇯🇵Gunma, Maebashi, Japan
Sapporo Medical University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Instituto de Investigación Clínica TyT
🇦🇷Caba, Argentina
Psoriahue Medicina Interdisciplinaria S.R.L
🇦🇷Caba, Argentina
KH der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
ULB Hopital Erasme
🇧🇪Bruxelles, Belgium
UNIV UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Kanazawa University Hospital
🇯🇵Ishikawa, Kanazawa, Japan
HOP Pontchaillou
🇫🇷Rennes, France
HOP Civil
🇫🇷Strasbourg, France
HOP Rangueil
🇫🇷Toulouse, France
HOP Brabois
🇫🇷Vandoeuvre-lès-Nancy, France
Universitätsklinikum Jena
🇩🇪Jena, Germany
Universitätsklinikum Köln (AöR)
🇩🇪Köln, Germany
Klinikum der Universität München AÖR
🇩🇪München, Germany
Tohoku University Hospital
🇯🇵Miyagi, Sendai, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Nagasaki, Japan
Osaka University Hospital
🇯🇵Osaka, Suita, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Osaka, Takatsuki, Japan
Grant Medical Foundation, Ruby Hall Clinic
🇮🇳Pune, India
Rambam Medical Center
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar-Saba, Israel
Western Galilee Hospital
🇮🇱Nahariya, Israel
Bnei Zion Medical Center, Haifa
🇮🇱Haifa, Israel
Istituto Ortopedico G.Pini
🇮🇹Milano, Italy
IRCCS San Raffaele
🇮🇹Milano, Italy
Wakayama Medical University Hospital
🇯🇵Wakayama, Wakayama, Japan
Soonchunhyang University Hospital Seoul
🇰🇷Seoul, Korea, Republic of
Hospital Selayang
🇲🇾Selangor, Malaysia
Oslo Universitetssykehus HF, Rikshospitalet
🇳🇴Oslo, Norway
Manila Doctors Hospital
🇵🇭Ermita, Philippines
National Medical Institute MSWiA
🇵🇱Warsaw, Poland
Prof Eleonora Reicher Memorial Institute of Rheumatology
🇵🇱Warsaw, Poland
C.M.D.T.A. NEOMED, Brasov
🇷🇴Brasov, Romania
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron-Barcelona-47683
🇪🇸Barcelona, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
University Hospital Zurich
🇨🇭Zürich, Switzerland
Maharaj Nakom Chiangmai Hospital
🇹🇭Chiangmai, Thailand
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Firat University Hospital
🇹🇷Elazig, Turkey
Chopda Medicare and Research Centre Pvt Ltd
🇮🇳Nashik, India
Centro de Investigaciones Metabolicas (CINME)-C.A.B.A-61553
🇦🇷C.a.b.a, Argentina
STAT Research
🇦🇷Caba, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Hospital Italiano de La Plata
🇦🇷La Plata, Argentina
Centro de Investigaciones Medicas Mar del Plata
🇦🇷Mar del Plata, Argentina
Royal Prince Alfred Hospital
🇦🇺Camperdown, Sydney, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
Edumed - Educacao e Saude SA
🇧🇷Curitiba, Brazil
Hospital do RIM - UNIFESP
🇧🇷São Paulo, Brazil
St. Paul's Hospital (Vancouver)
🇨🇦Vancouver, British Columbia, Canada
Mount Sinai Hospital-Toronto-18157
🇨🇦Toronto, Ontario, Canada
Centro Internacional de Estudios Clínicos (CIEC)
🇨🇱Comuna De Recoleta, Chile
Clínica Dermacross S.A.
🇨🇱Vitacura, Chile
Peking Union Medical College Hospital
🇨🇳Beijing, China
Peking University Third Hospital
🇨🇳Beijing, China
The First Affiliated Hospital Of Bengbu Medical College
🇨🇳Bengbu, China
The First Hospital of Jilin University
🇨🇳Changchun, China
West China Hospital
🇨🇳Chengdu, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
The third affiliated hospital of Sun Yat-Sen University
🇨🇳Guangzhou, China
Bacau County Hospital
🇷🇴Bacau, Romania
The Second Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, China
The First Affiliated Hospital of Ningbo University
🇨🇳Ningbo, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Wenzhou Med College
🇨🇳Wenzhou, China
Wuhan Union Hospital
🇨🇳Wuhan, China
Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T
🇨🇳Wuhan, China
Institute of Rheumathology Prague
🇨🇿Prague 2, Czechia
Aarhus University Hospital
🇩🇰Aarhus N, Denmark
Kuopio University Hospital
🇫🇮Kuopio, Finland
TYKS
🇫🇮Turku, Finland
HOP Annecy-Genevois
🇫🇷Epagny Metz-Tessy, France
HOP Hôtel-Dieu
🇫🇷Nantes, France
HOP Cochin
🇫🇷Paris, France
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
🇩🇪Frankfurt, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Westfälische Wilhelms-Universität Münster
🇩🇪Münster, Germany
General Hospital of Athens "Laiko"
🇬🇷Athens, Greece
St John's Medical College
🇮🇳Bangalore, India
Post Graduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Sree Sudheendra Medical Mission
🇮🇳Ernakulam, India
Institute of Post Graduate Medical Education and Research
🇮🇳Kolkata, India
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
🇮🇳Maharashtra, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Krishna Institute of Medical Sciences
🇮🇳Secunderabad, India
Connolly Hospital Blanchardstown
🇮🇪Dublin 15, Ireland
The Chaim Sheba Medical Center Tel HaShomer
🇮🇱Ramat Gan, Israel
Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
A.O. Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera Careggi
🇮🇹Firenze, Italy
Azienda Ospedaliera San Martino
🇮🇹Genova, Italy
Fujita Health University Hospital
🇯🇵Aichi, Toyoake, Japan
University of Fukui Hospital
🇯🇵Fukui, Yoshida-gun, Japan
Kyoto University Hospital
🇯🇵Kyoto, Kyoto, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hanyang University Medical Center
🇰🇷Seoul, Korea, Republic of
University of Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Investigacion y Biomedicina de Chihuahua S.C.
🇲🇽Chihuahua, Mexico
Centro Integral en Reumatologia, SA. de CV.
🇲🇽Guadalajara, Mexico
Medical Care & Research SA de CV
🇲🇽Merida, Mexico
Leids Universitair Medisch Centrum (LUMC)
🇳🇱Leiden, Netherlands
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
Waikato Hospital
🇳🇿Hamilton, Waikato, New Zealand
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Medvin Clinical Research-Covina-67001
🇺🇸Covina, California, United States
Southern California Scleroderma and Rheumatology Center
🇺🇸Inglewood, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Medvin Clinical Research-Whittier-69033
🇺🇸Whittier, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Mayo Clinic - Florida
🇺🇸Jacksonville, Florida, United States
Iris Research and Development
🇺🇸Plantation, Florida, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
St. Luke's Medical Center-Quezon-59457
🇵🇭Quezon City, Philippines
Malopolska Clinical Research
🇵🇱Krakow, Poland
Medical Center Hetmanska
🇵🇱Poznan, Poland
ULS de Almada -Seixal, E. P. E. - Hospital Garcia de Orta
🇵🇹Almada, Portugal
Military Medical Institute- National Research Institute
🇵🇱Warsaw, Poland
Aqua Clinic (AquaMed Consulting SRL- juridic)
🇷🇴Constanta, Romania
Singapore General Hospital
🇸🇬Singapore, Singapore
Hospital Clínico de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Dr. Peset
🇪🇸Valencia, Spain
Clinical Rheumatology Research Center Sahlgrenska
🇸🇪Gothenburg, Sweden
Kantonsspital St.Gallen
🇨🇭St. Gallen, Switzerland
China Medical University Hospital
🇨🇳Taichung, Taiwan
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
Ramathibodi Hospital
🇹🇭Ratchathewi, Thailand
Akdeniz Universitesi Tip Fakultesi -ANTALYA-33606
🇹🇷Antalya, Turkey
Chapel Allerton Hospital
🇬🇧Leeds, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Salford Royal
🇬🇧Salford, United Kingdom