A Study to Find Out How BIIB141 (Omaveloxolone) is Processed in the Body and to Learn More About Its Safety in Participants With Friedreich's Ataxia Aged 2 to 15 Years Old

NCT06054893 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 408-C-2001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, researchers will learn more about BIIB141, also known as omaveloxolone or SKYCLARYS®. This drug has been approved, or made available for doctors to prescribe, for people with Friedrich's Ataxia (FA) who are at least 16 years old. But, it is not yet available for children and teens with FA who are younger than 16 years old. The main objective of this study is to learn how BIIB141 is processed in the body of children and teens who are 2 to 15 years old. The main question researchers want to answer in this study is:

• How does the body process BIIB141 in children and teens?
• How many participants have medical problems during the study?
• Are there any changes in the participants' overall health during the study?
• Are there any changes in the participants' heart health?
• Are there any changes in how the participants move through puberty? Puberty is the time in someone's life when their body changes from a child to an adult. This study will be done as follows:
• Participants will be screened to see if they can join the study. The screening period will be up to 14 days, after which participants will check into their study research center.
• There are 2 parts to this study. During Part 1, participants will take a single dose of BIIB141. Participants will be in 1 of 7 different groups based on their age:
• Group A1: 12 to 15 years old, taking 150 milligrams (mg) of BIIB141
• Group A2: 12 to 15 years old, taking a dose of BIIB141 based on the data from Group A1
• Group B1: 7 to 11 years old, taking a dose of BIIB141 based on Group A1 data
• Group C1: 2 to 6 years old, taking a dose of BIIB141 based on Groups A1, A2, and B1 data
• Group A3: 12 to 15 years old, taking a dose of BIIB141 based on Groups A1, A2, and B1 data
• Group B2: 7 to 11 years old, taking a dose of BIIB141 based on Groups A1, A2, and B1 data
• Group C2: 2 to 6 years old, taking a dose of BIIB141 based on Group A1, A2, A3, B1, B2, and C1 data.
• During Part 2, participants from Part 1 will take BIIB141 once in the study research center. Cohort A1 will take 150 mg of BIIB141. Dose of Cohorts A2 and B1 will be based on data from Cohort A1, dose of Cohorts C1, A3 and B2 will be based on data from Cohorts A1, A2 and B1, while Cohort C2's dose will be based on all the other groups. Participants will then take it once a day at home.
• After leaving the study research center in Part 2, participants will return for tests at Week 4, Week 12, Week 24, and then every 24 weeks. Participants will also be contacted by telephone at Week 2, Week 8, and Week 18.
• Participants will be in this study for up to 240 weeks.

Conditions

Friedreich Ataxia

Keywords

Friedreich's ataxia; FA; RTA 408; Omaveloxolone

Outcome Measures

Primary Outcomes (20)

• Part 1: Apparent Clearance (CL/F) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Maximum Concentration (Cmax) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Volume of Distribution (V/F) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Area Under the Plasma Concentration-Time Curve From 0 Extrapolated to Infinity (AUC0-∞) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Area Under the Plasma Concentration-Time Curve From 0 to tlast (AUC0-tlast) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Individual Steady-State AUC0-24 (AUC0-24,ss) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Individual Steady-State Cmax (Cmax,ss) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 1: Concentration at the end of a 24-Hour Dosing Interval (Ctrough,ss) of Omaveloxolone

  Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours

• Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose results in death, in the view of investigator, places the participant at immediate risk of death (life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect or is medically important event.

  From Day 1 up to the end of study (up to Week 240)

• Part 2: Number of Participants With Clinically Significant Abnormality in Clinical Laboratory Assessments

  From Day 1 up to Week 240

• Part 2: Number of Participants With Clinically Significant Abnormality in Vital Signs

  Vital signs, including blood pressure (BP), heart rate (HR), and oral body temperature, will be assessed.

  From Day 1 up to Week 240

• Part 2: Number of Participants With Clinically Significant Abnormality in Electrocardiograms (ECGs)

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Echocardiogram (ECHO)

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Height

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Weight

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline Body Mass Index (BMI)

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Tanner Assessment

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Paediatric Growth (Height)

  From Day 1 up to Week 240

• Part 2: Number of Participants With Change from Baseline in Paediatric Growth (Weight)

  From Day 1 up to Week 240

Secondary Outcomes (4)

• Part 1: Number of Participants With AEs and SAEs

  From Day 1 up to Day 22

• Part 1: Number of Participants With Abnormality in Clinical Laboratory Assessments

  From Day 1 up to Day 22

• Part 1: Number of Participants With Abnormality in Vital Signs

  From Day 1 up to Day 22

• Part 1: Number of Participants With Abnormality in ECGs

  From Day 1 up to Day 22

Study Arms (7)

Part 1 and 2: Cohort A1

EXPERIMENTAL

Cohort A1 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, 150 milligrams (mg), capsule, on Day 1 of the treatment period of part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian population pharmacokinetics (popPK) analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort A2

EXPERIMENTAL

Cohort A2 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort B1

EXPERIMENTAL

Cohort B1 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A2. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort C1

EXPERIMENTAL

Cohort C1 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort A3

EXPERIMENTAL

Cohort A3 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort B2

EXPERIMENTAL

Cohort B2 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A3. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Part 1 and 2: Cohort C2

EXPERIMENTAL

Cohort C2 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohorts A1, A2, A3, B1, B2, and C1 to select the dose in part 1, followed by the same dose in part 2 up to week 240 or commercial availability whichever comes first. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses.

Drug: Omaveloxolone

Interventions

Omaveloxolone DRUG

Administered as specified in the treatment arm

Also known as: RTA 408, SKYCLARYS, BIIB141

Part 1 and 2: Cohort A1; Part 1 and 2: Cohort A2; Part 1 and 2: Cohort A3; Part 1 and 2: Cohort B1; Part 1 and 2: Cohort B2; Part 1 and 2: Cohort C1; Part 1 and 2: Cohort C2

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Have genetically confirmed FA.
• Have a left ventricular ejection fraction ≥ 40% (based on ECHO performed at Screening Visit).
• During screening, during the treatment period, and until 28 days following administration of the last dose of omaveloxolone, females of childbearing potential must practice at least 1 of the acceptable methods of birth control.
• During screening, during the treatment period, and until 28 days after the last dose of omaveloxolone, fertile males who have female partners of childbearing potential must practice one of the acceptable methods of birth control.

You may not qualify if:

• Have uncontrolled diabetes (haemoglobin A1c \[HbA1c\] \>11.0%).
• Have B-type natriuretic peptide (BNP) level \>200 picograms per milliliter (pg/mL) at screening.
• Have a history of clinically significant (CS) left-sided heart disease and/or CS cardiac disease, with the exception of mild to moderate cardiomyopathy associated with FA.
• Presence of outflow tract obstruction defined as a peak instantaneous gradient \>50 mmHg (based on ECHO performed at screening).
• Have taken any moderate or strong inhibitors and/or inducers of cytochrome P450 3A4 within the 7 days prior to Day 1 or plan to take during study participation (eg, itraconazole, carbamazepine, phenytoin, ciprofloxacin, grapefruit juice, cannabidiol, fluconazole, fluvoxamine, verapamil, diltiazem).
• Have a history of CS liver disease (eg, fibrosis, cirrhosis, hepatitis), or have clinically relevant deviations in laboratory tests at screening
• Plan to or have participated in any other interventional clinical study within the 30 days prior to Day 1.
• Have a cognitive impairment that may preclude ability to comply with study procedures, in the opinion of the investigator.
• Be unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator.
• Have previously documented mitochondrial respiratory chain disease.
• Have a history of thromboembolic events within the past 5 years.
• Plan to or have taken anticoagulant therapy within 30 days prior to Day 1 with the exception of a daily low dose aspirin (up to 81 mg).
• Plan to or have scheduled surgical treatment for scoliosis or foot deformity during the study.
• Have had significant suicidal ideation within 30 days prior to Screening Visit, as per investigator judgment, or any history of suicide attempt.
• For females, be pregnant or breastfeeding.

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

omaveloxolone

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Central Study Contacts

US Biogen Clinical Trial Center

CONTACT

866-633-4636; clinicaltrials@biogen.com

Global Biogen Clinical Trial Center

CONTACT

clinicaltrials@biogen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 26, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): February 21, 2030
• Study Completion (Estimated): November 22, 2030
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)