A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 121
- 试验地点
- 59
- 主要终点
- Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52
研究概览
简要总结
To investigate if Riociguat is effective in the treatment of systemic sclerosis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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, ie, 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 visit
- •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.
排除标准
- •Limited cutaneous SSc (systemic sclerosis) at screening
- •Major surgery (including joint 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/1.73 m^2 (Modification of Diet in Renal Disease formula) or on dialysis at the screening visit. Patients entering the trial with eGFR 15-29 mL/min/1.73 m^2 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
- •Pulmonary disease with FVC < 45% of predicted or DLCO (hemoglobin-corrected) < 40% of predicted at screening
- •Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
- •Not permitted prior and concomitant medication
- •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.
研究组 & 干预措施
Riociguat
Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.
干预措施: Riociguat (Adempas, BAY63-2521) (Drug)
Placebo
Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52
时间窗: Baseline to week 52
The mRSS is a validated physical examination method for estimating skin thickness. It correlates with biopsy measures of collagen in the dermis and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 (higher score means worse situation) and is used to categorize severity of SSc. A decrease in the mean change of mRSS shows mRSS improved.
次要结局
- CRISS (American College of Rheumatology Composite Response Index for Clinical Trials) at Week 52 Reported as Number of Participants With a CRISS Probability >=0.60 or <0.60 From Baseline to Week 52(Week 52)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 52(Baseline to week 52)
- Change From Baseline in Patient's Global Assessment Score to Week 52(Baseline to week 52)
- Change From Baseline in Physician's Global Assessment Score to Week 52(Baseline to week 52)
- Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52(Baseline to week 52)