Systemic Sclerosis
Conditions
Brief summary
Nerandomilast is being developed to help people with systemic sclerosis by potentially improving symptoms and slowing disease progression. This study is open to adults who are at least 18 years old and have systemic sclerosis (SSc). People can join the study if they have limited or diffuse cutaneous SSc with disease onset within 7 years of the first non-Raynaud's symptom. The purpose of this study is to find out whether a medicine called nerandomilast helps people with systemic sclerosis. This study also aims to find out how well nerandomilast is tolerated in people with systemic sclerosis. Participants are put into 2 groups randomly, which means by chance. One group takes nerandomilast tablets and the other group takes placebo tablets. Placebo tablets look like nerandomilast tablets but do not contain any medicine. Participants take the tablets twice a day. Participants are in the study for 1 to about 4 years. During this time, they visit the study site regularly and get phone calls from the site staff. During study visits participants regularly have blood samples taken and doctors check changes in skin thickening, lung function, and internal organs, overall health and the safety and tolerability of study treatment in people with SSc. The results are compared between the groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGPlacebo matching nerandomilast formulation 1
Film-coated tablets
DRUGPlacebo matching nerandomilast formulation 2
Film-coated tablets
DRUGNerandomilast formulation 1
Film-coated tablets
DRUGNerandomilast formulation 2
Film-coated tablets
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. 2. Patients must be at least 18 years of age and fulfil the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria for SSc. 3. Patients must be diagnosed with limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc), as defined by LeRoy et al. (1988). 4. Disease onset (defined by first non-RP \[Raynaud's phenomenon\] symptom) must be within 7 years of Visit 1. 5. Trial participants with dcSSc must have evidence of active disease during screening. 6. Trial participants with lcSSc must have evidence of active disease during screening. LcSSc patients must be anti-centromere antibody (ACA) negative. 7. FVC % predicted ≥45% at Visit 1. 8. Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) % predicted ≥25% corrected for haemoglobin (Hb) at Visit 1. 9. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control. 10. Patients may be either untreated or on stable treatment with permitted immunosuppressive/immunomodulatory agents and/or nintedanib. All treatments must remain stable prior to Visit 2 and during the screening period
Exclusion criteria
1. Active, unstable, or uncontrolled vasculitis within 8 weeks prior to Visit 1 or during the screening period. 2. Any suicidal behaviour in the past 2 years. 3. Any suicidal ideation of type 4 or 5 on the C-SSRS in the past 3 months. Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to the first occurrence of disease progression or all-cause death | up to 4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in mRSS at Week 52 | At baseline and at Week 52. | The modified Rodnan Skin Score (mRSS) measures skin thickness and is the sum of scores from 17 surface anatomic areas rated on a 0-3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold). The total mRSS ranges from 0 (best possible outcome) to 51 (worst possible outcome). |
| Change from baseline in HAQ-DI score at Week 52 | At baseline and at Week 52. | Health Assessment Questionnaire Disability Index (HAQ-DI) is used frequently in rheumatological disorders including SSc, assessing function/activities of daily living with 20 items in 8 categories, namely dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Each category has at least 2 sub-category questions. Within each category, patients report the amount of difficulty they have in performing the specific sub-category items. There are four response options ranging from "no difficulty" to "unable to do", scored 0 to 3. A global score will be calculated from the category scores with higher scores indicating more severe disability. |
| Change from baseline in FVC [mL] at Week 52 | At baseline and at Week 52. | Forced vital capacity (FVC) |
| Disease improvement as defined by rCRISS-25 at Week 52 | At baseline and at Week 52. | Revised composite response index in systemic sclerosis (rCRISS) is a composite outcome measure developed for SSc that includes PRO and clinician-reported outcome (ClinRO) measures: * mRSS * FVC % * HAQ-DI * Patient Global Assessment (PGA) of overall health status * Clinician Global Assessment (CGA) of overall health status For rCRISS-25 a patient has improvement on at least 2 of the 5 core set measures and without worsening on more than 1 core set measure. The improvement or worsening must be at least 25% relative change from the baseline for 4 core set measures (or ≥5% relative change from baseline for FVC % predicted). |
| Time to first occurrence of confirmed absolute decline from baseline in FVC % predicted ≥5% (for patients with ILD at baseline) or newly diagnosed ILD (for patients without ILD at baseline) or death | up to 4 years | — |
| Time to first occurrence of absolute increase in mRSS ≥5 points and relative increase from baseline in mRSS ≥25% or death | up to 4 years | — |
| Time to first occurrence of adjudicated SSc-related related clinically meaningful disease progression or complication or death | up to 4 years | — |
| Time to all-cause death | up to 4 years | — |
| Change from baseline in Systemic Sclerosis Impact of Disease (ScleroID) score at Week 52 | At baseline and at Week 52. | The Systemic Sclerosis Impact of Disease (ScleroID) is a patient reported outcome (PRO) measure specifically developed to assess how SSc affects a person's life. The ScleroID has 10 items and it covers 10 domains. Every item is rated on a 0-10 numeric rating scale and the individual scores are computed using a weighted sum, resulting in a final score ranging from 0 to 10. A higher score means a higher impact of disease. |
| Change from baseline in digital ulcer total burden at Week 52 | At baseline and at Week 52. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Romania, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States, Vietnam
Contacts
CONTACTBoehringer Ingelheim
Outcome results
None listed