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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05559580




Registration number
NCT05559580
Ethics application status
Date submitted
26/09/2022
Date registered
29/09/2022
Date last updated
27/06/2024

Titles & IDs
Public title
A Study in People With Systemic Sclerosis to Test Whether Avenciguat (BI 685509) Has an Effect on Lung Function and Other Systemic Sclerosis Symptoms
Scientific 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
Secondary ID [1] 0 0
2022-500332-11-00
Secondary ID [2] 0 0
1366-0031
Universal Trial Number (UTN)
Trial acronym
VITALISScE™
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Scleroderma, Systemic 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avenciguat (BI 685509)
Treatment: Drugs - Placebo

Experimental: Avenciguat (BI 685509) - Avenciguat (BI 685509)

Placebo comparator: Placebo - Placebo


Treatment: Drugs: Avenciguat (BI 685509)
Avenciguat (BI 685509)

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks
Timepoint [1] 0 0
48 weeks.
Secondary outcome [1] 0 0
Absolute change from baseline in Modified Rodnan Skin Score (mRSS) at Week 48 in study participants with diffuse cutaneous systemic sclerosis (dcSSc)
Timepoint [1] 0 0
At baseline and at week 48.
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
At baseline and at week 48.
Secondary outcome [3] 0 0
Absolute change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48
Timepoint [3] 0 0
At baseline and at week 48.
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
At week 48.
Secondary outcome [5] 0 0
Absolute change from baseline in forced vital capacity (FVC) (mL) at Week 48
Timepoint [5] 0 0
At week 48.
Secondary outcome [6] 0 0
Absolute change from baseline in forced vital capacity (FVC) (% predicted) at Week 48
Timepoint [6] 0 0
At baseline and at week 48.
Secondary outcome [7] 0 0
Absolute change from baseline in the Patient Global Assesment (PGA) Visual Analog Scale (VAS) score at Week 48
Timepoint [7] 0 0
At baseline and at week 48.
Secondary outcome [8] 0 0
Absolute change from baseline in the Clinician Global Assessment (CGA) Visual Analog Scale (VAS) score at Week 48
Timepoint [8] 0 0
At baseline and at week 48.
Secondary outcome [9] 0 0
Composite measure of Raynaud's phenomenon (RP) activity at Week 48
Timepoint [9] 0 0
Week 48.
Secondary outcome [10] 0 0
Absolute change from baseline in Digital ulcer (DU) net burden at Week 48
Timepoint [10] 0 0
At baseline and at week 48.
Secondary outcome [11] 0 0
Time to treatment failure
Timepoint [11] 0 0
48 weeks.
Secondary outcome [12] 0 0
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)
Timepoint [12] 0 0
48 weeks.
Secondary outcome [13] 0 0
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)
Timepoint [13] 0 0
48 weeks.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/11/2025
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
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Alabama
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Texas
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Argentina
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Caba
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Roma
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Aichi, Toyoake
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Fukui, Yoshida-gun
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Fukuoka, Kitakyushu
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Gunma, Maebashi
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Hokkaido, Sapporo
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Ishikawa, Kanazawa
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Kyoto, Kyoto
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Miyagi, Sendai
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Nagasaki, Nagasaki
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Osaka, Suita
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Osaka, Takatsuki
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Tokyo, Bunkyo-ku
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Wakayama, Wakayama
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Leiden
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Nijmegen
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Hamilton
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Bucharest
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Bucuresti
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Cluj-Napoca
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Romania
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Constanta
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Romania
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Ramnicu-Valcea
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Singapore
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Singapore
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Spain
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Barcelona
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Madrid
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Valencia
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Sweden
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Göteborg
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Switzerland
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St. Gallen
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Switzerland
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Zürich
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Taiwan
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Taichung
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Taiwan
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Taipei
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Thailand
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Chiang Mai
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Thailand
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Hat Yai
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Muang
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Thailand
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Ratchathewi
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Turkey
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Antalya
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Turkey
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Elazig
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United Kingdom
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Leeds
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United Kingdom
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Liverpool
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London
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United Kingdom
State/province [141] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT05559580
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boehringer Ingelheim
Address 0 0
Country 0 0
Phone 0 0
1-800-243-0127
Fax 0 0
Email 0 0
clintriage.rdg@boehringer-ingelheim.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05559580