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™)

• ClinicalTrials.gov Identifier: NCT05559580
• Recruitment Status: Recruiting
• First Posted: September 29, 2022
• Last Update Posted: May 14, 2024
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: September 26, 2022
• First Posted Date: September 29, 2022
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: November 24, 2022
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 26, 2022): Rate of decline in forced vital capacity (FVC) (mL) over 48 weeks [ Time Frame: 48 weeks. ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 11, 2023)

• Absolute change from baseline in Modified Rodnan Skin Score (mRSS) at Week 48 in study participants with diffuse cutaneous systemic sclerosis (dcSSc) [ Time Frame: 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).
• 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 [ Time Frame: 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 Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48 [ Time Frame: 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.
• 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 [ Time Frame: 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 forced vital capacity (FVC) (mL) at Week 48 [ Time Frame: At week 48. ]
• Absolute change from baseline in forced vital capacity (FVC) (% predicted) at Week 48 [ Time Frame: At baseline and at week 48. ]
• Absolute change from baseline in the Patient Global Assesment (PGA) Visual Analog Scale (VAS) score at Week 48 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 48. ]
• Absolute change from baseline in Digital ulcer (DU) net burden at Week 48 [ Time Frame: At baseline and at week 48. ]
• Time to treatment failure [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 48 weeks. ]

Original Secondary Outcome Measures (submitted: September 26, 2022)

• American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) score at Week 48 [ Time Frame: 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.
• Revised Composite Response Index in Systemic Sclerosis (CRISS) score at Week 48 [ Time Frame: At week 48. ]
  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 Modified Rodnan Skin Score (mRSS) at Week 48 [ Time Frame: 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).
• Absolute change from baseline in forced vital capacity (FVC) (% predicted) at Week 48 [ Time Frame: At baseline and at week 48. ]
• Absolute change from baseline in the Patient Global Assesment (PGA) Visual Analog Scale (VAS) score at Week 48 [ Time Frame: 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 [ Time Frame: 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.
• Absolute change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Week 48 [ Time Frame: 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.
• Composite measure of Raynaud's phenomenon (RP) activity at Week 48 [ Time Frame: Week 48. ]
• Absolute change from baseline in Digital ulcer (DU) net burden at Week 48 [ Time Frame: At baseline and at week 48. ]
• Time to treatment failure [ Time Frame: 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Patients, investigators, central reviewers, and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial will remain blinded regarding the randomised treatment assignments until the database is declared ready for analysis according to the sponsor's Standard Operating Procedures (SOPs).

Primary Purpose: Treatment

• Condition: Scleroderma, Systemic

Intervention

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

Study Arms

• Experimental: Avenciguat (BI 685509)
  Avenciguat (BI 685509)
  Intervention: Drug: Avenciguat (BI 685509)
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 26, 2022): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 28, 2025
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

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

Administrative Information

• NCT Number: NCT05559580
• Other Study ID Numbers: 1366-0031; 2022-500332-11-00 ( Registry Identifier: CTIS )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.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.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: May 2024