Friedreich Ataxia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGOmaveloxolone
Administered as specified in the treatment arm.
DRUGPlacebo
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
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
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 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change From Baseline in Upright Stability Score (USS) Subscale E of Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52 | 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 2A: Change From Baseline in USS Subscale E of mFARS at Week 52 | Baseline (Week 52 of Part 1), 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 2B: Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (TESAE) | From the first dose of the study drug in Part 2B up to the end of follow-up period in Part 2B (up to Week 104) | — |
| Part 2B: Number of Participants With Change From Baseline in Cardiac Function Assessed by Echocardiogram (ECHO) at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2B: Change From Baseline in Height at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2B: Change From Baseline in Weight at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2B: Change From Baseline in Body Mass Index (BMI) at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2B: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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 2B: Percentage of Participants at Each Tanner Stage at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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 2B: Number of Participants at Each Tanner Stage at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change From Baseline in Friedreich's Ataxia-Health Index (FA-HI) at Week 52 | Baseline, Week 52 | 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. |
| Part 1: Change From Baseline in Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 52 | 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 1: Change From Baseline in Patient Global Impressions-Severity (PGI-S) at Week 52 | Baseline, Week 52 | 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. |
| Part 1: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) at Week 52 | Baseline, Week 52 | 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. |
| Part 1: Change From Baseline in Friedreich's Ataxia-Activities of Daily Living (FA-ADL) | Baseline, Week 52 | 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. |
| Part 1: 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 (up to Week 52) | — |
| Part 1: Number of Participants With Change From Baseline in Cardiac Function Assessed by ECHO at Week 52 | Baseline, Week 52 | — |
| Part 1: Change From Baseline in Height at Week 52 | Baseline, Week 52 | — |
| Part 1: Change From Baseline in Weight at Week 52 | Baseline, Week 52 | — |
| Part 1: Change From Baseline in Body Mass Index (BMI) at Week 52 | Baseline, Week 52 | — |
| Part 1: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Week 52 | Baseline, Week 52 | 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 1: Percentage of Participants at Each Tanner Stage at Week 52 | Baseline, Week 52 | 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 1: Number of Participants at Each Tanner Stage at Week 52 | Baseline, Week 52 | 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 1: Plasma Concentrations of Omaveloxolone | Pre-dose and post-dose on Day 1, Weeks 4, 12 and 26 | — |
| Part 2A: Change From Baseline in USS Subscale E of mFARS at Week 104 | Baseline (Week 52 of Part 1), Week 104 | 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 2A: Change from baseline in mFARS at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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 2A: Number of Participants With TEAE and TESAE | From the first dose of the study drug in Part 2A up to the end of follow-up period in Part 2A (up to Week 104) | — |
| Part 2A: Number of Participants With Change From Baseline in Cardiac Function Assessed by ECHO at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2A: Change From Baseline in Height at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2A: Change From Baseline in Weight at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2A: Change From Baseline in BMI at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | — |
| Part 2A: Change From Baseline in C-SSRS at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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 2A: Percentage of Participants at Each Tanner Stage at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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 2A: Number of Participants at Each Tanner Stage at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 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 2A: Plasma Concentrations of Omaveloxolone | Pre-dose and post-dose on Day 1, Weeks 4, 12 and 26 | — |
| Part 2B: Change From Baseline in mFARS Including USS at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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). |
| Parts 2A and 2B: Change From Baseline in FA-HI at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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. |
| Parts 2A and 2B: Change From Baseline in PGI-S at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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. |
| Parts 2A and 2B: Change From Baseline in CGI-S at Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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. |
| Parts 2A and 2B: Change from baseline in FA-ADL at Part 2A Weeks 52 and Week 104 | Baseline (Week 52 of Part 1), Weeks 52 and 104 | 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. |
Countries
Australia, Austria, Brazil, Canada, Denmark, France, Germany, India, Ireland, Italy, Netherlands, Saudi Arabia, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPatient Navigator
CONTACTUS Biogen Clinical Trial Center
STUDY_DIRECTORMedical Director
Biogen
Outcome results
None listed