A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Diffuse Cutaneous Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 9
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of JBT-101 in adult subjects with diffuse cutaneous systemic sclerosis.
详细描述
Part A of the study is an interventional, double-blind, randomized, placebo-control design will be used to test safety, tolerability, pharmacokinetics, and efficacy of JBT-101 in subjects ≥ 18 and ≤ 70 years of age with active diffuse cutaneous systemic sclerosis. The screening period is up to 28 days, with 84 days treatment period and 28 days follow-up off active treatment.
Part B of the study is an interventional, open-label design will be used. All subjects who complete dosing in Part A without permanent discontinuation of study drug and who pass repeat safety screening will be eligible for enrollment. The screening period is up to 28 days, with a 364 day treatment period and 28 day follow up after last dose of JBT-101.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diffuse cutaneous systemic sclerosis
- •Have skin thickening from SSc in a body area suitable for repeat biopsy
- •Disease duration ≤ 3 years from the first non-Raynaud's phenomenon or >3 years and ≤ 6 years from the first non-Raynaud's phenomenon and high sensitivity C-reactive protein > 3 mg/L, high sensitivity interleukin-6 > 5 pg/mL, or increase in mRSS ≥ 5 points over the last 6 months with total RSS ≥
- •Stable treatment for SSc for at least 28 days before Visit 1
- •Completion of dosing in Part A without permanent discontinuation of study product because of safety or tolerability reasons.
- •Exclusion Criteria (Part A and B):
- •Severe or unstable systemic sclerosis
- •Significant diseases or conditions other than systemic sclerosis that may influence response to the study product or safety;
- •Any one of the following values for laboratory tests at Screening:
- •A positive pregnancy test (or at Visit 1);
- •Hemoglobin < 10 g/dL
- •Neutrophils < 1.0 x 10^9/L
- •Platelets < 75 x 10^9/L
- •Creatinine clearance < 50 ml/min according to modified Cockcroft-Gault equation
- •Serum transaminases > 2.0 x upper normal limit
- •Total bilirubin ≥ 1.5 x upper limit of normal
- •Any other condition that, in the opinion of the Principal Investigator, is clinically significant and may put the subject at greater safety risk, influence response to study product, or interfere with study assessments.
排除标准
- 未提供
研究组 & 干预措施
Placebo
Placebo bid on Days 1-84.
干预措施: Placebo (Drug)
JBT-101 5 mg/20 mg bid
JBT-101 5 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg twice a day (bid) on Days 29-84.
干预措施: JBT-101 (Drug)
JBT-101 5 mg/20 mg bid
JBT-101 5 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg twice a day (bid) on Days 29-84.
干预措施: Placebo (Drug)
JBT-101 20 mg/20 mg bid
JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.
干预措施: JBT-101 (Drug)
JBT-101 20 mg/20 mg bid
JBT-101 20 mg q am and placebo q pm on Days 1-28, then JBT-101 20 mg bid on Days 29-84.
干预措施: Placebo (Drug)
JBT-101 20 mg bid/20 mg bid
JBT-101 20 mg bid on Days 1-84.
干预措施: JBT-101 (Drug)
Part B Open-label
JBT-101 20 mg bid on Days 1-364
干预措施: Part B Open-Label Extension (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events From Baseline at Day 113
时间窗: Part A: Day 113
The overall number of subjects with TEAE's per treatment group during active dosing (Days 1-84) plus the 28 day follow-up.
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Day 85 and 113
时间窗: Day 85 and Day 113
CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction \< 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.
次要结局
- CRISS Individual Component (Patient Global Assessment Score) Change From Baseline(Day 85 and 113)
- CRISS Individual Components (mRSS Total Score) Change From Baseline.(Day 85 and 113)
- CRISS Individual Component (Physician Global Assessment Score) Change From Baseline(Day 85 and 113)
- CRISS Individual Component (HAQ-DI Score) Change From Baseline.(Day 85 and 113)
- CRISS Individual Component (FVC Percent Predicted) Change From Baseline(Day 85 and 113)