Clinical trial NCT05559580: A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Scleroderma, Systemic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-09-29
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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