A Phase 3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Omaveloxolone (BIIB141) in Participants With Friedreich's Ataxia Aged 2 to < 16 Years
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Biogen
- 入组人数
- 255
- 试验地点
- 56
- 主要终点
- Part 2 OLE: Change From Baseline in Body Mass Index (BMI)
研究概览
简要总结
In this study, researchers will learn more about omaveloxolone, also known as BIIB141 or SKYCLARYS®. Omaveloxolone is already approved for people with Friedreich's Ataxia (FA) who are 16 years of age or older. However, it is not yet available for younger teens and children. The main goal of this study is to learn how omaveloxolone affects symptoms of FA and its safety in younger participants between the ages of 2 and 15 years old.
The main questions researchers want to answer in this study are:
- How does omaveloxolone affect the participants' FA symptoms?
- How many participants have adverse events during the study?
- Are there any changes in the participants' overall health or heart health? Adverse events are health problems that may or may not be caused by the study drug.
Researchers will use the modified Friedreich's Ataxia Rating Scale (mFARS) to test nerve function. The mFARS tests movement ability, balance, coordination, speech, and arm and leg functions.
They will also use a number of questionnaires to learn more about participants' quality of life, muscle strength, and ability to perform daily tasks. Researchers will also note any changes as participants go through puberty.
Finally, researchers will learn more about how the body processes omaveloxolone in children and teenagers.
This study will be done in 2 parts as follows:
- Participants will be screened for up to 4 weeks to check if they can join the study.
- In Part 1, participants will be randomly assigned to take either omaveloxolone or a placebo by mouth once a day for about 1 year. A placebo looks like the study drug but contains no real medicine.
- Part 1 will be double blind. This means that the participants, study doctor, and site staff will not know if the participants are receiving omaveloxolone or a placebo.
- Including screening, participants will have up to 9 clinic visits and 1 phone call during Part 1. If a participant does not join Part 2, they will have another safety follow-up phone call a month after their last dose of omaveloxolone.
- Participants who complete Part 1 will move onto Part 2 where everyone will receive omaveloxolone for about 2 years.
- During Part 2, participants will have up to 8 clinic visits and 1 phone call. Participants will also have a follow-up phone call about a month after they stop taking omaveloxolone.
- In total, participants will have up to 17 clinic visits and 3 phone calls. Each participant will be in the study for up to 3 years.
详细描述
The primary objective of Part 1 is to evaluate the efficacy of omaveloxolone as measured by upright stability score (USS) and the secondary objectives are to evaluate the efficacy of omaveloxolone as measured by additional secondary efficacy outcomes, safety of omaveloxolone and the plasma concentration of omaveloxolone after single and multiple dose administration.
The primary objective of Part 2A is to evaluate the efficacy of omaveloxolone and the secondary objectives are to characterize the efficacy of omaveloxolone as measured by additional secondary outcomes, evaluate the safety and tolerability of omaveloxolone and plasma concentration of omaveloxolone after single and multiple dose administration.
The primary objective for Part 2B is to evaluate the safety and tolerability of long-term omaveloxolone use and the secondary objective is to evaluate the efficacy of omaveloxolone following long-term use.
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)
盲法说明
Part 1 of the study is placebo-controlled and Part 2 is open-label.
入排标准
- 年龄范围
- 2 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1: Key inclusion criteria:
- •Diagnosed with genetically confirmed Friedreich's Ataxia (FA), i.e., homozygous for guanine-adenine-adenine (GAA) repeat expansion in intron-1 of the frataxin gene, or GAA repeat expansion in 1 allele and with point mutations or deletions, or other non-GAA expansion mutations in the other allele.
- •Symptomatic for FA as confirmed by clinician assessment. a. Children 7 to < 16 years must also have an upright stability score (USS) score of 10 to ≤ 34 at baseline
- •Part 1: Key
排除标准
- •Glycosylated hemoglobin A1C (HbA1c) > 11%
- •B-type natriuretic peptide (BNP) > 200 picograms per milliliter (pg/mL) at screening
- •Ejection fraction (EF) < 40% [based on echocardiogram (ECHO) performed at screening visit]
- •Clinically significant cardiac disease except mild to moderate cardiomyopathy
- •Part 2A: Eligibility criteria:
- •They have completed Part 1 of the study and no discontinuation criteria have been met.
- •Safety and tolerability data from Part 1 are supportive of continuation in the judgement of the investigator.
- •Part 2B: Eligibility criteria:
- •Participants have completed Part 1 of the study and no discontinuation criteria have been met.
- •Safety and tolerability data from Part 1 are supportive of continuation in the judgement of the Investigator.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 1: Placebo
Participants will receive placebo, orally, QD for up to 52 weeks in Part 1 of the study.
干预措施: Placebo (Drug)
Part 2A Continued Efficacy Evaluation: Omaveloxolone
Participants will receive a single oral dose of omaveloxolone, QD for up to 104 weeks in Part 2A of the study.
干预措施: Omaveloxolone (Drug)
Part 2B Safety: Omaveloxolone
Participants will receive a single oral dose of open-label omaveloxolone, QD for up to 104 weeks in Part 2B of the study.
干预措施: Omaveloxolone (Drug)
Part 1: Omaveloxolone
Participants will receive a single oral dose of omaveloxolone once a day (QD) for up to 52 weeks in Part 1 of the study.
干预措施: Omaveloxolone (Drug)
结局指标
主要结局
Part 2 OLE: Change From Baseline in Body Mass Index (BMI)
时间窗: Baseline (Week 52) up to Week 104
Part 2 OLE: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO)
时间窗: Baseline (Week 52) up to Week 104
Part 2 OLE: Change From Baseline in Height
时间窗: Baseline (Week 52) up to Week 104
Part 2 OLE: Change From Baseline in Weight
时间窗: Baseline (Week 52) up to Week 104
Part 1 RCT: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS)
时间窗: Baseline, Week 52
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
Part 2 OLE: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE)
时间窗: From the first dose of the study drug in Part 2 up to the end of follow-up period in Part 2 (up to Week 105)
Part 2 OLE: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: Baseline (Week 52) up to Week 104
The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment of individuals ≥ 6 years of age. The C-SSRS is a clinical interview providing a summary of both ideation and behavior that can be administered by the clinician during any evaluation or risk assessment to identify the level and type of suicidality present. The assessment includes "yes" or "no" responses for 5 questions each, related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation, from 1 to 5, with 5 being the most severe.
Part 2 OLE: Percentage of Participants at Each Tanner Stage
时间窗: Baseline (Week 52) up to Week 104
Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.
Part 2 OLE: Number of Participants at Each Tanner Stage
时间窗: Baseline (Week 52) up to Week 104
Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.
次要结局
- Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI)(Baseline, Week 52)
- Part 1 RCT: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS)(Baseline, Week 52)
- Part 1 RCT: Change From Baseline in Patient Global Impressions-Severity (PGI-S)(Baseline, Week 52)
- Part 1 RCT: Change From Baseline in Clinical Global Impressions-Severity (CGI-S)(Baseline, Week 52)
- Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL)(Baseline, Week 52)
- Part 1 RCT: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE)(From first dose of study drug up to end of follow up period in Part 1 RCT (up to Week 54))
- Part 1 RCT: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO)(Baseline, Weeks 26 and 52)
- Part 1 RCT: Change From Baseline in Height(Baseline up to Week 52)
- Part 1 RCT: Change From Baseline in Weight(Baseline up to Week 52)
- Part 1 RCT: Change From Baseline in Body Mass Index (BMI)(Baseline up to Week 52)
- Part 1 RCT: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline up to week 52)
- Part 1 RCT: Percentage of Participants at Each Tanner Stage(Screening and Week 52)
- Part 1 RCT: Number of Participants at Each Tanner Stage(Screening and Week 52)
- Part 1 RCT: Plasma Concentrations of Omaveloxolone(Pre-dose and post-dose on Day 1, Weeks 4, 12 and 26)
- Part 2 OLE: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS), Including Upright Stability Score (USS)(Baseline (Week 52) up to Week 104)
- Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL)(Baseline (Week 52) up to Week 104)
- Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI)(Baseline (Week 52) up to Week 104)
- Part 2 OLE: Change From Baseline in Patient Global Impressions-Severity (PGI-S)(Baseline (Week 52) up to Week 104)
- Part 2 OLE: Change From Baseline in Clinical Global Impressions-Severity (CGI-S)(Baseline (Week 52) up to Week 104)