A Phase III, Multicentre, Randomised, Double-Blind Study to Assess the Safety and Efficacy of Emactuzumab vs. Placebo in Subjects With Tenosynovial Giant Cell Tumour
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 128
- 试验地点
- 84
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is a multicenter, Phase 3, randomised, double-blind, placebo-controlled study, which aims to evaluate the efficacy and safety of the investigational drug emactuzumab for the treatment of patients with localized or diffuse TGCT where surgical removal of the tumor is not viewed as an option.
The study consists of two parts. In Part 1, eligible subjects will be assigned in a 2:1 ratio to receive either emactuzumab or matching placebo in a double-blind fashion, that will be administered in total 5 times as an intravenous (i.v.) infusion once every 2 weeks. This will be followed by an observation period of 3 months leading to a total duration of 24 weeks in Part 1. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. Part 2 is a long-term double-blind follow-up phase of the subjects on emactuzumab or placebo. Subjects assigned to placebo in Part 1 have the option, subject to eligibility, to crossover to receive open-label emactuzumab in Part 2. Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment under certain circumstances.
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
- •Age >12 years
- •Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations through surgical joint damage, and/or subject has an anticipated high risk of early recurrence as determined by a multidisciplinary tumour board or equivalent, or any other morbidity associated with the surgery, and/or surgical treatment is not expected to improve the clinical outcomes of the subject.
- •Measurable disease: longest diameter ≥20 mm.
- •Adequate organ and bone marrow function
- •If a woman of childbearing potential (WOCBP), must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception
- •Participants must have given written consent
排除标准
- •If a female, the subject is pregnant or breast feeding.
- •Medical conditions, including auto-immune, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study.
- •Known metastatic TGCT or other active cancer that requires concurrent or planned treatment
- •Received systemic therapy for TGCT (investigational or approved) targeting CSF-1 or CSF-1R or any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) within 3 months prior to screening
- •Any surgery, chemotherapy or radiotherapy within 3 months of screening
- •Unresolved clinically significant toxicity from a previous treatment or any history of serious liver toxicity.
- •Current or chronic history of liver disease.
- •Inadequate renal and liver function
- •Systemic antiretroviral therapy within 3 months of baseline
- •Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994) including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.
研究组 & 干预措施
Group 1 in Part 1/Part 2: Emactuzumab
Group 1: Subjects receiving emactuzumab administered intravenously (i.v) on Day(D)1 and repeated once every two weeks (Q2W) for a total of 5 times, followed by an observation period of 3 months leading to a total period of 24 weeks in Part 1 and continued with a follow-up phase in Part 2. Eligible Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment in Part 2.
干预措施: Emactuzumab (Drug)
Group 2 in Part 1 and Part 2: Placebo
Group 2: Subjects receiving placebo administered intravenously (i.v) on D1 and repeated once every two weeks (Q2W) for 5 times followed by an observation period of 3 months to a total period of 24 weeks in Part 1. In Part 2, Eligible Subjects will have the option to receive open-label emactuzumab, administered by i.v once every 2 weeks (Q2W) for a total of 5 times.
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Day 0 - Day 180 (6 months)
Objective Response Rate (ORR = complete response \[CR\] + partial response \[PR\]) by 6 months from initiation of therapy according to RECIST v1.1 based on independent, blinded central review
次要结局
- Physical Function(up to 24 months)
- Range of Motion (ROM)(up to 24 months)
- Worst Stiffness(up to 24 months)
- Worst Pain(up to 24 months)
- Quality of Life (QoL)(up to 24 months)
- Duration of response (DoR)(up to 24 months)
- Tumour volume score (TVS)(up to 24 months)
- Surgical Intervention Rate(up to 24 months)