A Study to Learn More About the Effects and Long-Term Safety of Omaveloxolone (BIIB141) in Children and Teens With Friedreich's Ataxia
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 does the body process omaveloxolone? * How many participants have adverse events during the study? Adverse events are health problems that may or may not be caused by the study drug. * Are there any changes in the participants' overall health or heart health? 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. More specifically, researchers will check participants' balance, coordination, movement, and ability to perform daily tasks using the Upright Stability Score (USS). The USS is part of the mFARS questionnaire.
Researchers will also use other questionnaires to learn more about participants' symptoms, quality of life, ability to perform daily living activities, and how severe participants think their disease is. Researchers will also note any changes as participants go through puberty. Some participants may also be invited to take part in interviews about their experiences during the study or wear devices that measure movement and physical activity during daily life.
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 doctors, and study 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 finish Part 1 may move onto Part 2. During Part 2, participants who are at least 7 years old will be randomly assigned to receive either 150 mg or 250 mg of omaveloxolone once a day for about 104 weeks.
Participants younger than 7 years old will receive 150 mg of omaveloxolone once a day for about 104 weeks. * 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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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 reported by the participant and/or the parent/caregiver a. Children 7 to < 16 years must also have an upright stability score (USS) score of 10 to ≤ 34 at baseline
Exclusion criteria
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06953583
Intervention or treatment
DRUG: Omaveloxolone
DRUG: Placebo
Conditions
- Friedreich Ataxia
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Research sites nearby
Closest Location:
Murdoch Childrens Research Institute (MCRI)
Select from list below to view details:
Murdoch Childrens Research Institute (MCRI)
Parkville, Victoria, Australia
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Who is running the clinical trial?
Biogen
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part 1: Omaveloxolone
| Drug: Omaveloxolone |
PLACEBO_COMPARATOR: Part 1: Placebo
| Drug: Placebo |
EXPERIMENTAL: Part 2A Continued Efficacy Evaluation: Omaveloxolone
| Drug: Omaveloxolone |
EXPERIMENTAL: Part 2B Safety: Omaveloxolone
| Drug: Omaveloxolone |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 RCT: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS) | 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). | Baseline, Week 52 |
| Part 2 OLE: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE) | Not Specified | 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: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO) | Not Specified | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Height | Not Specified | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Weight | Not Specified | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Body Mass Index (BMI) | Not Specified | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) | 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. | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Percentage of Participants at Each Tanner Stage | 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. | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Number of Participants at Each Tanner Stage | 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. | Baseline (Week 52) up to Week 104 |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI) | The FA-HI is a participant reported survey that assesses overall disease burden on a 100-point scale, with 0 representing no disease burden and 100 representing the maximum level of disease burden containing 113 symptoms questions representing 18 symptomatic subscales. | Baseline, Week 52 |
| Part 1 RCT: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS) | 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). | Baseline, Week 52 |
| Part 1 RCT: Change From Baseline in Patient Global Impressions-Severity (PGI-S) | PGI-S will be conducted for participants 7 to \< 16 years of age. These are clinically meaningful outcome measures that are participant-relevant across all age groups and disease severities for this population. PGI -S is a 1-item questionnaire where the response is recorded on a 4-point scale scored as: 1-normal, 2-mild, 3-moderate, or 4-severe. | Baseline, Week 52 |
| Part 1 RCT: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) | The CGI-S will be conducted for all enrolled participants, 2 to \< 16 years of age. The CGI-S rating evaluates the severity of individual symptoms and treatment response in participants with mental disorders. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. | Baseline, Week 52 |
| Part 1 RCT: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL) | Participants will answer the 9 questions of the FA-ADL survey in an interview style conducted by any site staff. The FA-ADL survey assesses 9 concepts: (1) speech; (2) swallowing; (3) cutting food and handling utensils; (4) dressing; (5) personal hygiene; (6) falling; (7) walking; (8) quality of sitting position; and (9) bladder function. | Baseline, Week 52 |
| Part 1 RCT: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE) | Not Specified | 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) | Not Specified | Baseline, Weeks 26 and 52 |
| Part 1 RCT: Change From Baseline in Height | Not Specified | Baseline up to Week 52 |
| Part 1 RCT: Change From Baseline in Weight | Not Specified | Baseline up to Week 52 |
| Part 1 RCT: Change From Baseline in Body Mass Index (BMI) | Not Specified | Baseline up to Week 52 |
| Part 1 RCT: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) | 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. | Baseline up to week 52 |
| Part 1 RCT: Percentage of Participants at Each Tanner Stage | 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. | Screening and Week 52 |
| Part 1 RCT: Number of Participants at Each Tanner Stage | 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. | Screening and Week 52 |
| Part 1 RCT: Plasma Concentrations of Omaveloxolone | Not Specified | 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) | 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). | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL) | Participants will answer the 9 questions of the FA-ADL survey in an interview style conducted by any site staff. The FA-ADL survey assesses 9 concepts: (1) speech; (2) swallowing; (3) cutting food and handling utensils; (4) dressing; (5) personal hygiene; (6) falling; (7) walking; (8) quality of sitting position; and (9) bladder function. Every participant will be instructed to answer the 9 questions. Total scores on FA-ADL will be used as a secondary endpoint to assess efficacy in participants 7 to \< 16 years of age. | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI) | The FA-HI is a participant reported survey that assesses overall disease burden on a 100-point scale, with 0 representing no disease burden and 100 representing the maximum level of disease burden containing 113 symptoms questions representing 18 symptomatic subscales. | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Patient Global Impressions-Severity (PGI-S) | PGI-S will be conducted for participants 7 to \< 16 years of age. These are clinically meaningful outcome measures that are participant relevant across all age groups and disease severities for this population. PGI -S is a 1-item questionnaire where the response is recorded on a 4-point scale scored as: 1-normal, 2-mild, 3-moderate, or 4- severe. | Baseline (Week 52) up to Week 104 |
| Part 2 OLE: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) | The CGI-S will be conducted for all enrolled participants, 2 to \< 16 years of age. The CGI-S rating evaluates the severity of individual symptoms and treatment response in participants with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the participant's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. | Baseline (Week 52) up to Week 104 |
References
Clinical Trials Gov: A Study to Learn More About the Effects and Long-Term Safety of Omaveloxolone (BIIB141) in Children and Teens With Friedreich's AtaxiaOther trials to consider
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