The purpose of this study is to investigate the effectiveness and safety of riociguat (BAY 63-2521) in patients with diffuse cutaneous systemic sclerosis.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Connective tissue disorders (excl congenital)
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary: Change in mRSS from baseline to week 52
Secondary outcome
N/A
Background summary
Diffuse cutaneous SSc is one of the most severely incapacitating and
life-threatening rheumatic diseases. Based on preclinical in vitro and in vivo
data demonstrating that riociguat was safe and efficacious in different models
of fibrotic diseases including scleroderma, the hypothesis is that riociguat
may bring significant clinical benefit to patients with scleroderma. This study
aims to recruit patients with dcSSc. The rationale is: a) there is a better
understanding of the natural history of dcSSc than lcSSc, and b) dcSSc is a
subset of SSc in which more rapid progression in disease occurs with worse
prognosis, and where there is a high unmet need for effective treatment.
Study objective
The purpose of this study is to investigate the effectiveness and safety of
riociguat (BAY 63-2521) in patients with diffuse cutaneous systemic sclerosis.
Study design
Randomized (1:1), double-blind, placebo-controlled, parallel-group,
multicenter, multinational study
Intervention
The optimal dose should be determined during the initial 10-week dose titration
period based on monitoring of the patient*s SBP and well-being. The recommended
starting dose is 0.5 mg TID. The intervals between drug intake should be 6 - 8
hours. The dosage should be increased by 0.5 mg increments no sooner than 2
weeks apart to 1 mg, 1.5 mg, 2 mg, and 2.5 mg TID, resulting in a maximum total
daily dose of 7.5 mg. Patients should be maintained on lower doses if higher
doses are not tolerated (minimum dose of 0.5 mg TID, see Section 5.2.1). After
the dose titration period, riociguat should be continued at the optimal dose
for the duration of the maintenance period.
Study burden and risks
Because riociguat has not been studied in patients with diffuse cutaneous
systemic sclerosis it can`t even say at this point whether you can may benefit
from this treatment.
A disadvantage may be that you have to come more often than you are used to the
hospital and additional blood samples and skin biopsies can be taken.
Furthermore, with placebo you can`t expect the potential effects of the
treatment of riociguat. Potential adverse effects on Riociguat..
The knowledge produced by this drug, could contribute to improved future
treatment of patients with diffuse systemic sclerodemie.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
- Men or women aged 18 years and older
- Systemic sclerosis, as defined by ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) 2013 criteria
- dcSSc (diffuse cutaneous systemic sclerosis) according to the LeRoy criteria, i.e., skin fibrosis proximal to the elbows and knees in addition to acral fibrosis.
- Disease duration of * 18 months (defined as time from the first non*Raynaud*s phenomenon manifestation)
- * 10 and * 22 mRSS (modified Rodnan skin score) units at the screening visit
- FVC (forced vital capacity) * 45% of predicted at screening
- DLCO (diffusion capacity of the lung for carbon monoxide) * 40% of predicted (hemoglobin-corrected) at screening
-Negative serum pregnancy test in a woman of childbearing potential at the screening
Exclusion criteria
- Limited cutaneous SSc (systemic sclerosis) at screening
- Major surgery within 8 weeks prior to screening
- 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
- Estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m2 or on dialysis at the screening visit. Patients entering the trial with eGFR 15-29mL/min/1.73m2 will be undergo additional monitoring of renal function
- Any prior history of renal crisis
- Sitting SBP (systolic blood pressure) < 95 mmHg at the screening visit
- Sitting heart rate < 50 beats per minute (BPM) at the screening visit
- Left ventricular ejection fraction < 40% prior to screening
- Any form of pulmonary hypertension as determined by right heart catheterization
- Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
- Not permitted prior and concomitant medication (updated)
- Pregnant or breast feeding women
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001353-16-NL |
| ClinicalTrials.gov | NCT02283762 |
| CCMO | NL50735.091.14 |