Effectiveness and safety of riociguat in patients with sclerosis of the ski
- Conditions
- diffuse cutaneous systemic sclerosis (dcSSc)MedDRA version: 20.0Level: LLTClassification code 10012977Term: Diffuse systemic sclerosisSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2014-001353-16-GB
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 121
1.Written informed consent
2. Men or women aged 18 years and older
3. Systemic sclerosis, as defined by ACR/EULAR 2013 criteria
4. dcSSc according to the LeRoy criteria, i.e. skin fibrosis proximal to the elbows and knees in addition to acral fibrosis
5. Disease duration of = 18 months (defined as time from the first non-Raynaud’s phenomenon manifestation)
6. = 10 and = 22 mRSS units at the screening visit
7. FVC = 45% of predicted at screening
8. DLCO = 40% of predicted (hemoglobin-corrected) at screening
9. Negative serum pregnancy test in a woman of childbearing potential at the screening visit
10. Women of childbearing potential must agree to use adequate contraception when sexually active. Adequate contraception” is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies since signing of the informed consent form until 30 (+5) days after the last study drug administration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45
1. Limited cutaneous SSc at screening
2. Major surgery (including joint surgery) within 8 weeks prior to screening
3. Hepatic insufficiency classified as Child-Pugh C
• Patients with isolated AST or ALT >3xULN or bilirubin >2xULN can be included in the trial under the condition of additional monitoring during the trial
4. Estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m2 (Modification of Diet in Renal Disease formula) or on dialysis at the screening visit. Patients entering the trial with eGFR 15-29 mL/min/1.73m2 will be undergo additional monitoring of renal function
- Because the MDRD formula is thought to cause significant bias for Japanese patients, the equation for Japanese patients is: 194 x serum creatinine (mg/dL) -1.094 x Age -0.287 x 0.739 (if female).
5. Any prior history of renal crisis
6. Sitting SBP < 95 mmHg at the screening visit
7. Sitting heart rate < 50 beats per minute (BPM) at the screening visit
8. Left ventricular ejection fraction < 40% prior to screening
9. Any form of pulmonary hypertension as determined by right heart catheterisation
10. Pulmonary disease with FVC < 45% of predicted or DLCO (hemoglobin-corrected) < 40% of predicted at screening
11. Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
12. Any history of bronchial artery embolisation or massive haemoptysis is defined as acute bleeding >240 mL in a 24 hour period or recurrent bleeding >100 mL/day over consecutive days)
13. Not permitted prior and concomitant medication (updated)
14. pregnant or breast feeding women
15. Women of childbearing potential not willing to use adequate contraception and not willing to agree to 4-weekly pregnancy testing from Visit 1 (first administration of study drug) onwards until 30 (+5) days after last study drug intake.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: Key secondary objective:<br>• CRISS at Week 52, consisting of five variables: mRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score (from SHAQ patient reported outcome)<br>Further secondary objective:<br>• HAQ-DI domain (separately from the SHAQ as part of the calculation of the CRISS algorithm). <br>• Patient's global assessment<br>• Physician's global assessment<br>• Change in FVC (forced vital capacity) % predicted ;Primary end point(s): Change in mRSS from baseline to Week 52 ;Timepoint(s) of evaluation of this end point: week 52;Main Objective: The primary objective of this study is to assess the efficacy of riociguat administered 3 times a day (TID) as compared with placebo in terms of change in the mRSS from baseline to Week 52.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Key secondary endpoint:<br>• CRISS, consisting of five variables: mRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score (from SHAQ patient reported outcome)<br>Further secondary endpoints:<br>• HAQ-DI domain (separately from the SHAQ as part of the calculation of the CRISS algorithm). <br>• Patient's global assessment<br>• Physician's global assessment<br>• Change in FVC (forced vital capacity) % predicted ;Timepoint(s) of evaluation of this end point: week 52