A Phase 2, Proof-Of-Concept, Multicenter, Randomized, Double-Blind, Placebo- Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) in Subjects With Systemic Sclerosis With Interstitial Lung Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 23
- 试验地点
- 56
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of pomalidomide in the treatment of patients with systemic sclerosis with interstitial lung disease.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Pomalidomide
Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase and for up to 2 years during the open-label extension phase.
干预措施: Pomalidomide (CC-4047) (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From the start of study drug to 28 days after last dose; Treatment Phase median duration of treatment was 358 and 320 days for Placebo and Pomalidomide; Extension phase median duration of treatment was 161 days and 194 days for Placebo and pomalidomide.
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE is any AE that began or worsened on or after the start of study drug through 28 days after the last dose. A treatment-related TEAE is a TEAE which was considered by the investigator to be related to study drug. The severity/intensity of AEs was assessed by the investigator as Mild (asymptomatic or mild symptoms; intervention not indicated), Moderate (symptoms cause moderate discomfort, intervention may be required), or Severe (symptoms cause severe discomfort/pain, requiring medical intervention, inability to perform daily activities). A serious AE is any AE that: - Resulted in death; - Was life-threatening; - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Constituted an important medical event.
Change From Baseline in University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Total Score at Week 52/Early Termination
时间窗: Baseline and Week 52 (or Treatment Phase Early Termination visit)
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets gastrointestinal (GI) activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health (except for Questions 15 and 31 which are scored as 0 (better health) or 1 (worse health). The total score is calculated as the average of the first 6 scale scores (excluding constipation) which captures overall burden (severity) of SSc-associated GIT. The overall score ranges from 0 to 3, where higher scores indicate more severe symptoms.
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
时间窗: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 52
Forced vital capacity (FVC) is a pulmonary function test and is the volume of air in the lungs that can forcibly be blown out after a full inhalation. Percent predicted values are based comparison between the participant's measured value with expected FVC for someone of the same sex, age and height (reference value). For the analysis of FVC, the baseline value was defined as the average of all values between Screening and Baseline (inclusive), and the average of Weeks 48 and 52 was treated as the Week 52 value, to reduce the total data variability at the key time points.
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination
时间窗: Baseline and Week 52 (or the Treatment Phase Early Termination visit)
Improvement in skin thickening is associated with improved survival and may be useful as a surrogate measurement in clinical studies. The mRSS is an assessment tool which is used to evaluate the extent and severity of the skin thickening associated with systemic sclerosis (SSc). Seventeen body areas were evaluated on a 4-point scale (0 \[normal\], 1 \[mild\], 2 \[moderate\]), or 3 \[severe\]). The total score, which is the sum of the 17 individual body assessments, can range from 0 to 51.
次要结局
- Change From Baseline in Percent Predicted Forced Vital Capacity Over Time(Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156)
- Change From Baseline in Modified Rodnan Skin Score Over Time(Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time(Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination(Week 156 or the Extension Phase Early Termination visit)
- Change From Baseline in Dyspnea Magnitude of Task at Week 12(Week 12)
- Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination(Week 52 or at the Treatment Phase Early Termination visit)
- Change From Baseline in Dyspnea Functional Impairment at Week 64(Week 64)
- Change From Baseline in Dyspnea Functional Impairment at Week 12(Week 12)
- Change From Baseline in Dyspnea Functional Impairment at Week 24(Week 24)
- Change From Baseline in Dyspnea Functional Impairment at Week 76(Week 76)
- Change From Baseline in Dyspnea Magnitude of Task at Week 24(Week 24)
- Change From Baseline in Dyspnea Magnitude of Task at Week 76(Week 76)
- Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination(Week 52 or at the Treatment Phase Early Termination visit)
- Change From Baseline in Dyspnea Magnitude of Task at Week 64(Week 64)
- Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination(Week 156 or the Extension Phase Early Termination visit)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 12(Week 12)
- Oxygen Saturation Over Time(Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).)
- Pharmacokinetic Parameters of Pomalidomide in Plasma(Day 1 and week 4 pre-dose and up to 24 hours post-dose.)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 24(Week 24)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination(Week 52 or at the Treatment Phase Early Termination visit)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 76(Week 76)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 64(Week 64)
- Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination(Week 156 or at the Extension Phase Early Termination visit)