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

Scleroderma, Systemic Clinical Trial

— VITALISScE™  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05559580
• Other study ID #: 1366-0031
• Secondary ID: 2022-500332-11-0
• Status: Recruiting
• Phase: Phase 2
• Start date: November 24, 2022
• Est. completion date: November 28, 2025

Study information

• Verified date: June 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 28, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Drug:
• Avenciguat (BI 685509)
Avenciguat (BI 685509)
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Centro de Investigaciones Metabólicas (CINME)	C.a.b.a
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Instituto de Investigación Clínica TyT	Caba
Argentina	Psoriahue Medicina Interdisciplinaria S.R.L	Caba
Argentina	STAT Research	Caba
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Centro de Investigaciones Médicas Mar del Plata	Mar del Plata
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Medical University of Graz State Hospital - University Hospital Graz	Graz
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	UNIV UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Brazil	Edumed - Educacao e Saude SA	Curitiba
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo
Brazil	Hospital do RIM - UNIFESP	São Paulo
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	St. Paul's Hospital	Vancouver	British Columbia
Chile	Centro Internacional de Estudios Clínicos (CIEC)	Comuna De Recoleta
Chile	Clínica Dermacross S.A.	Vitacura
China	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	3rd Affiliated Hosp of Sun yet-sen University	Guangzhou
China	Guangdong Provincial People's Hospital	Guangzhou
China	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	Tongji Hospital Affiliated Tongji Medical College Huazhong University of S & T	Wuhan
China	Wuhan Union Hospital	Wuhan
Czechia	Institute of Rheumathology Prague	Prague
Czechia	Medical Plus s.r.o., Rheumatology Outpatient Clinic	Uherske Hradiste
Denmark	Aarhus University Hospital	Aarhus N
Finland	Kuopio University Hospital	Kuopio
Finland	TYKS	Turku
France	HOP Annecy-Genevois	Epagny Metz-Tessy
France	HOP Hôtel-Dieu	Nantes
France	HOP Cochin	Paris
France	HOP Pontchaillou	Rennes
France	HOP Civil	Strasbourg
France	HOP Rangueil	Toulouse
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP	Frankfurt
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Köln (AöR)	Köln
Germany	Klinikum der Universität München AÖR	München
Germany	Westfälische Wilhelms-Universität Münster	Münster
Greece	General Hospital of Athens "Laiko"	Athens
Greece	General Hospital of Athens "Laiko"	Athens
India	St John's Medical College	Bangalore
India	Post Graduate Institute of Medical Education and Research	Chandigarh
India	Sree Sudheendra Medical Mission	Kochi
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	Grant Medical Foundation, Ruby Hall Clinic	Pune
India	Krishna Institute of Medical Sciences	Secunderabad
Israel	Bnei Zion Medical Center, Haifa	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar-Saba
Israel	Western Galilee Hospital	Nahariya
Israel	The Chaim Sheba Medical Center Tel HaShomer	Ramat Gan
Italy	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	IRCCS San Raffaele	Milano
Italy	Istituto Ortopedico G.Pini	Milano
Italy	Azienda Ospedaliera Policlinico di Modena	Modena
Italy	AOU Policlinico Umberto I	Roma
Italy	Poli Univ A. Gemelli	Roma
Italy	Università degli Studi Campus Bio-Medico	Roma
Japan	Japan Community Healthcare Organization Chukyo Hospital	Aichi, Nagoya
Japan	Fujita Health University Hospital	Aichi, Toyoake
Japan	University of Fukui Hospital	Fukui, Yoshida-gun
Japan	Hospital of the University of Occupational and Environmental Health	Fukuoka, Kitakyushu
Japan	Gunma University Hospital	Gunma, Maebashi
Japan	Hokkaido University Hospital	Hokkaido, Sapporo
Japan	Sapporo Medical University Hospital	Hokkaido, Sapporo
Japan	Kanazawa University Hospital	Ishikawa, Kanazawa
Japan	Kyoto University Hospital	Kyoto, Kyoto
Japan	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	Nippon Medical School Hospital	Tokyo, Bunkyo-ku
Japan	Wakayama Medical University Hospital	Wakayama, Wakayama
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Soonchunhyang University Hospital Seoul	Seoul
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Selayang	Selangor
Mexico	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	Oaxaca Site Management Organization, S.C.	Oaxaca
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
New Zealand	Waikato Hospital	Hamilton
Philippines	Manila Doctors Hospital	Manila
Philippines	St. Luke's Medical Center	Quezon City
Poland	Malopolska Clinical Research	Krakow
Poland	Medical Center Hetmanska	Poznan
Poland	Military Medical Institute- National Research Institute	Warsaw
Poland	National Medical Institute MSWiA	Warsaw
Romania	C.M.D.T.A. NEOMED, Brasov	Brasov
Romania	Dr. Ion Cantacuzino Clinical Hospital, Bucharest	Bucharest
Romania	St. Mary's Clinical Hospital	Bucharest
Romania	S.C. Policlinica CCBR SRL, Bucuresti	Bucuresti
Romania	Cluj Napoca Clinical County Hospital	Cluj-Napoca
Romania	Aqua Clinic (AquaMed Consulting SRL- juridic)	Constanta
Romania	SC Medaudio Optica SRL	Ramnicu-Valcea
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Spain	Hospital Dr. Peset	Valencia
Sweden	Clinical Rheumatology Research Center Sahlgrenska	Göteborg
Switzerland	Kantonsspital St.Gallen	St. Gallen
Switzerland	University Hospital Zurich	Zürich
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Maharaj Nakom Chiangmai Hospital	Chiang Mai
Thailand	Songklanagarind Hospital	Hat Yai
Thailand	Srinagarind Hospital	Muang
Thailand	Ramathibodi Hospital	Ratchathewi
Turkey	Akdeniz Universitesi Tip Fakultesi	Antalya
Turkey	Firat University Hospital	Elazig
United Kingdom	Chapel Allerton Hospital	Leeds
United Kingdom	Aintree University Hospital	Liverpool
United Kingdom	Royal Free Hospital	London
United Kingdom	Salford Royal Hospital	Salford
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	The Emory Clinic	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	New York City Health and Hospitals/Kings County	Brooklyn	New York
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Medvin Clinical Research	Covina	California
United States	University of Florida	Gainesville	Florida
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Southern California Scleroderma and Rheumatology Center	Inglewood	California
United States	Mayo Clinic - Florida	Jacksonville	Florida
United States	University of California Los Angeles	Los Angeles	California
United States	Vanderbilt University Medical Center - Vanderbilt Lung Institute at 100 Oaks	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Iris Research and Development	Plantation	Florida
United States	Mayo Clinic	Scottsdale	Arizona
United States	Medvin Clinical Research	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Philippines,  Poland,  Romania,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks		48 weeks.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Absolute change from baseline in forced vital capacity (FVC) (mL) at Week 48		At week 48.
Secondary	Absolute change from baseline in forced vital capacity (FVC) (% predicted) at Week 48		At baseline and at week 48.
Secondary	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.
Secondary	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.
Secondary	Composite measure of Raynaud's phenomenon (RP) activity at Week 48		Week 48.
Secondary	Absolute change from baseline in Digital ulcer (DU) net burden at Week 48		At baseline and at week 48.
Secondary	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.
Secondary	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.
Secondary	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.

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