Rollover Study; Multicentre, Phase III, Open-label Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed Study PVO-1A-301 or PVO-1A-202/PVO-1A-204 and May Benefit From Palovarotene Therapy.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 61
- 试验地点
- 13
- 主要终点
- Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
研究概览
简要总结
The main objective of this study is to further evaluate the safety and efficacy of palovarotene in adult and paediatric participants with FOP.
The aim of the study is also to ensure treatment continuity to participants who have completed one of the parent studies (Study PVO-1A-301, Study PVO-1A-202 and Study PVO-1A-204) and who, in the investigator's judgement, may benefit from palovarotene therapy.
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
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did not previously withdraw consent from any of the parent studies to be eligible for Study CLIN-60120-
- •Participant must be ≥14 years of age (aligned with the age of treated participants in the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100% skeletally mature (if <18 years, based on assessments carried out at parent EOS Visit; if ≥18 years, automatically considered 100% skeletally mature) or have reached final adult height based on investigator's assessment, at the time the Study CLIN- 60120-452 informed consent is signed.
排除标准
- •History of allergy or hypersensitivity to retinoids, gelatin, lactose (note that lactose intolerance is not exclusionary) or palovarotene, or unresponsiveness to prior treatment with palovarotene.
- •Uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
- •Symptomatic vertebral fracture.
- •Intercurrent known or suspected non-healed fracture at any location;
- •Any other medical condition/clinically significant abnormalities that would expose the participant to undue risk or interfere with study assessments.
- •Amylase or lipase >2× above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
- •Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5× ULN.
- •Fasting triglycerides >400 mg/dL with or without therapy.
- •Suicidal ideation (type 4 or 5) or any suicidal behaviour at the Inclusion Visit as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Current use of vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
- •Exposure to synthetic oral retinoids other than palovarotene within 4 weeks of the Inclusion Visit.
- •Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
- •Use of concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
- •Palovarotene is reimbursed in the country where the study is being conducted.
- •Any reason that, in the opinion of the investigator, would lead to the inability of the participant and/or family to comply with the protocol.
研究组 & 干预措施
Palovarotene Chronic/Flare-Up Regimen
Chronic treatment: participants will receive 5 mg palovarotene or the dose received during participation in the parent study at the time of transition to Study CLIN-60120-452 or prior to interrupting/stopping palovarotene treatment.
Flare-up treatment: at the time of a flare-up (or substantial high-risk traumatic event likely to lead to a flare-up) participants will receive 20 mg palovarotene for 28 days, followed by 10 mg palovarotene for 56 days.
干预措施: Palovarotene (Drug)
结局指标
主要结局
Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events
时间窗: From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, 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 or significant medical event. A TEAE was defined as any AE that occurred after signing the informed consent form of this study or an ongoing AE from the parent study with a worsening in severity or relationship to the study treatment following transition to this study.
次要结局
- Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva(Up to approximately 32 months)
- Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30(Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30)
- Number of Participants With Flare-ups and Flare-up Outcomes(Months 6, 12, 18 and 24)
- Number of Participants With Flare-ups by Body Location(Months 6, 12, 18 and 24)
- Duration of Flare-up at Months 6, 12, 18 and 24(Months 6, 12, 18 and 24)
- Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24(Months 6, 12, 18 and 24)