A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease Followed by an Open-Label Extension Phase
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 14
- 主要终点
- Reduction in Primary Joint Contracture to 5° or Less
研究概览
简要总结
This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled phase and a nine-month open-label extension phase. Before treatment, eligible subjects were stratified by the primary joint type (30 metacarpophalangeal [MP] joints and 30 proximal interphalangeal [PIP] joints) and by severity of the primary joint contracture (ie, up to 50° or >50° for MP joints and up to 40° or >40° for PIP joints) and then randomized in a 2:1 ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie, 90-day evaluation after the first injection), all subjects were eligible to enter the open-label extension phase of the study in which they were followed for an additional nine months. Subjects who required further treatment because they either did not achieve reduction in contracture to 5° or less, the cord affecting the primary joint received placebo, another cord received less than three injections of AA4500, or they had untreated cords that were affecting other joints had the option to receive up to five additional injections of AA4500 0.58 mg in the open-label extension phase, with individual cords receiving up to three injections of AA4500.
This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 [NCT00528606] and AUX-CC-859 [NCT00533273]) and 7 non-pivotal studies were evaluated.
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
- •Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100°, for MP (80° for PIP) joints, caused by a palpable cord.
- •Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
- •Were naive to AA4500 treatment
- •Were judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.
排除标准
- •Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
- •Had received a treatment for advanced Dupuytren's disease, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug.
- •Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.
结局指标
主要结局
Reduction in Primary Joint Contracture to 5° or Less
时间窗: Within 30 days after last injection
Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
次要结局
- Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection(Baseline, Day 30 after last injection)
- Time to Reach Clinical Success in Primary Joint(Within 30 days after last injection)
- Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection(Baseline, Day 30 after last injection)
- Clinical Improvement in Non-Primary Joint After the First Injection(Baseline, Within 30 days after first injection)
- Percent Reduction From Baseline Contracture of Primary Joint After the First Injection(Baseline, Day 30 after first injection)
- Clinical Improvement in Non-Primary Joint After the Last Injection(Baseline, Within 30 days after last injection)
- Change From Baseline Range of Motion in Non-Primary Joint After the First Injection(Baseline, Day 30 after first injection)
- Clinical Improvement in Primary Joint After the Last Injection(Baseline, Within 30 days after last injection)
- Clinical Success in Primary Joint After the First Injection(Within 30 days after first injection)
- Clinical Improvement in Primary Joint After the First Injection(Baseline, Within 30 days after first injection)
- Change From Baseline Range of Motion in Primary Joint After the First Injection(Baseline, Day 30 after first injection)
- Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection(Within 30 days after last injection)
- Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection(Baseline, Day 30 after last injection)
- Time to Reach Clinical Success in Non-Primary Joint(Within 30 days after last injection)
- Clinical Success in Non-Primary Joint After the First Injection(Within 30 days after first injection)
- Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection(Baseline, Day 30 after first injection)
- Change From Baseline Range of Motion in Primary Joint After the Last Injection(Baseline, Day 30 after last injection)