A Phase II Randomized, Double -Blind, Placebo Controlled Study to Assess Safety, Tolerability and Effect on Tumor Size of MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This study, designed as a proof of concept study of MCS110 in pigmented villonodular synovitis, assessed the clinical response to MCS110 treatment in Pigmented Villonodular Synovitis (PVNS) patients, after a single or multiple intravenous doses of MCS110, using magnetic resonance imaging to assess tumor volume, and evaluated the pharmacokinetics/pharmacodynamics, safety and tolerability in this population.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, 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
MCS110
Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion.
干预措施: MCS110 (Drug)
Placebo
Part A: single-dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion) Part B: single dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion administered i.v. at Day 1, followed by 6 doses of placebo to match MCS110 (10 mg/kg)
干预措施: Placebo (Drug)
MCS110 3 mg/kg
Part C: MCS110 3 mg/kg (i.v. infusion)
干预措施: MCS110 (Drug)
MCS110 5 mg/kg
Part C: MCS110 5 mg/kg (i.v. infusion)
干预措施: MCS110 (Drug)
MCS110 10 mg/kg
Part C: MCS110 10 mg/kg (i.v. infusion)
干预措施: MCS110 (Drug)
MCS110 3 mg/kg & MCS110 10mg/kg
Part C: MCS110 3 mg/kg (i.v. infusion) & MCS110 10 mg/kg (i.v. infusion)
干预措施: MCS110 (Drug)
MCS110 5 mg/kg & MCS110 10mg/kg
Part C: MCS110 5 mg/kg (i.v. infusion) & MCS110 10 mg/kg (i.v. infusion)
干预措施: MCS110 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Approximately 2 years
Overall incidence of Adverse Events
Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
时间窗: Week 4
To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
时间窗: Up to 8 weeks post last dose
To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\].
Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
时间窗: Up to 8 weeks post last dose
Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 \& 10 mg/kg or 5 \& 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\]
Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
时间窗: Week 4
To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
次要结局
- Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).(Baseline, Week 4, Week 24, Week 104)
- Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes(Baseline Up to Week 104)
- Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)(Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr))
- Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)(Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr))
- Pharmacokinetics of MCS110 Maximum Concentration (Cmax)(Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr))
- Time to Relapse(Up to Week 104)
- Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study))
- Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study))
- Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire(Week 4, Week 24, up to 104 weeks)
- Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time(Baseline, Day 1, Day 85, Day 169)
- Number of Participants With Negative Anti-MCS110 Antibody(Baseline, throughout the study up to Day 505)
- Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion(Week 24/28, Week 104)
- Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)(Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104)
- Time to Surgery(Up to Week 104)
- Average of Health-Related Quality of Life Questionnaire Score for mHAQ(up to 104 weeks)
- Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study))
- Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study))
- Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)(Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study))