A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 16
- 主要终点
- Annualized New Heterotopic Ossification (HO)
研究概览
简要总结
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO) often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with cumulative and irreversible loss of movement and disability.
详细描述
One of the primary objectives was to evaluate the efficacy of palovarotene in decreasing new HO in participants with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, compared to untreated participants from Clementia's FOP natural history study (Study PVO-1A-001, NHS). The other primary objective was to evaluate the safety of palovarotene in participants with FOP.
This study was conducted in three parts. Part A was the main part of the study, Part B, the 2-year (24-month) extension and Part C was an up-to-2-year post last dose of study treatment follow-up for skeletally immature participants.
Participants in Part A and B received a chronic/flare-up dosing regimen of palovarotene for up to 4 years (48 months) as follows:
- Chronic treatment: orally administered 5 mg palovarotene once daily.
- Flare-up treatment: orally administered 20 mg palovarotene once daily for 4 weeks (28 days) followed by orally administered 10 mg palovarotene once daily for 8 weeks (56 days). Flare-up treatment may be extended until the Investigator determines that the flare-up has resolved.
Note that all dosing was weight-adjusted in skeletally immature participants (those under the age of 18 years with less than 90% skeletal maturity on hand/wrist x-rays performed at Screening).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local regulations).
- •Males or females at least 4 years of age.
- •No flare-up symptoms within the past 4 weeks, including at the time of enrollment.
- •Abstinent or using two highly effective forms of birth control.
- •Accessible for treatment and follow-up; able to undergo all study procedures including low-dose WBCT (excluding head) without sedation.
排除标准
- •Weight <10 kg.
- •Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
- •Amylase or lipase >2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
- •Elevated aspartate aminotransferase or alanine aminotransferase >2.5x ULN.
- •Fasting triglycerides >400 mg/dL with or without therapy.
- •Female subjects who are breastfeeding.
- •Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
- •Simultaneous participation in another clinical research study (other than palovarotene studies) within 4 weeks prior to Screening; or within five half-lives of the investigational agent, whichever is longer.
- •Any reason that, in the opinion of the Investigator, would lead to the inability of the subject and/or family to comply with the protocol.
研究组 & 干预措施
Palovarotene Chronic/Flare-Up Regimen
Participants received 5 mg palovarotene once daily for up to 48 months; and 20 mg palovarotene once daily for 28 days, followed by 10 mg for 56 days for flareups. (Dosing was adjusted for weight in skeletally immature subjects.)
干预措施: Palovarotene (Drug)
结局指标
主要结局
Annualized New Heterotopic Ossification (HO)
时间窗: Baseline (within one month of screening/Day 1) and up to 24 months
The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.
次要结局
- Percentage of Participants With Any New HO(From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months))
- Number of Body Regions With New HO(From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months))
- Percentage of Participants With Flare-Ups(Month 12)
- Ratio of Flare-Up Per Participant-Month of Exposure(From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months))