A Study to Learn About the Effects and Safety of RTA 408 (Omaveloxolone) in People Aged 16 to 40 With Friedreich's Ataxia

A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe)

In this study, researchers are learning more about RTA 408, also known as omaveloxolone, BIIB141, or SKYCLARYS®. The main goal of this study is to learn more about the safety of RTA 408 and how it affects physical effort, movement, coordination, and how participants feel in daily life.

The main questions researchers want to answer in this study are:

• How much physical effort can a participant produce during a cycling test after 12 weeks of treatment?
• How do scores on the modified Friedreich's Ataxia Rating Scale (mFARS) change after 48 weeks?

Researchers will use the modified Friedreich's Ataxia Rating Scale (mFARS) to measure how FA affects the nervous system. The mFARS looks at movement ability, balance, coordination, speech, and how well the arms and legs work.

They will also use a cycling test to measure physical effort, along with questionnaires to learn how participants feel and function in daily life.

Safety will also be tested using physical exams, vital sign checks, echocardiograms (ECHO), electrocardiograms (ECG), and blood and urine tests.

The study will be done in 2 main parts, followed by an optional Extension period:

• In Part 1, participants will be randomly assigned to take different doses of RTA 408 or a placebo by mouth once a day for 12 weeks. A placebo looks like the study drug but contains no real medicine.
• Researchers will compare these doses to decide which one to use in Part 2.
• In Part 2, a different group of participants will take either the chosen dose of RTA 408 (150 mg) or placebo once a day for 48 weeks.
• Participants who complete Part 1 or Part 2 may be able to join an Extension period, where everyone receives RTA 408.
• In the Extension period, participants will continue to receive RTA 408 until the drug becomes commercially available or until they leave the study
• Participants in Part 1 will have up to 9 study visits and 2 phone calls. If they do not move onto the Extension period, they will stay in the study for up to 20 weeks.
• Participants in Part 2 will have up to 10 study visits and 3 phone calls. If they do not move onto the Extension period, they will stay in the study for up to 61 weeks.
• Participants in the Extension period will have 2 visits in the first month, followed by visits every 6 months.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Placebo; Drug: Omaveloxolone Capsules, 2.5 mg; Drug: Omaveloxolone Capsules, 5 mg; Drug: Omaveloxolone Capsules, 10 mg; Drug: Omaveloxolone Capsules, 20 mg; Drug: Omaveloxolone Capsules, 40 mg; Drug: Omaveloxolone Capsules, 80 mg; Drug: Omaveloxolone Capsules, 160 mg; Drug: Omaveloxolone Capsules, 300 mg; Drug: Omaveloxolone Capsules, 150 mg

Detailed Description

Friedreich's ataxia is an autosomal recessive cerebellar ataxia caused by triplet-repeat expansions. The causative mutation is a trinucleotide (GAA) repeat expansion in the first intron of the frataxin gene, leading to impaired transcription of frataxin. The pathological consequences of frataxin deficiency include a severe disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation, and an increased sensitivity to oxidative stress.

A hallmark of Friedreich's ataxia is impairment of antioxidative defense mechanisms, which play a major role in disease progression. Studies have demonstrated that nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling is grossly impaired in participants with Friedreich's ataxia. Therefore, the ability of omaveloxolone (RTA 408) to activate Nrf2 and induce antioxidant target genes is hypothesized to be therapeutic in participants with Friedreich's ataxia.

This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone (RTA 408) in the treatment of participants with Friedreich's ataxia.

Part 1: The first part of this study will be a randomized, placebo-controlled, double-blind, dose-escalation study to evaluate the safety of omaveloxolone (RTA 408) at various doses in participants with Friedreich's ataxia.

Part 2: The second part of this study is a randomized, placebo-controlled, double-blind, parallel-group study to evaluate the safety and efficacy of omaveloxolone (RTA 408) 150 mg in participants with Friedreich's ataxia. Participants enrolled in Part 2 will be randomized 1:1 to receive omaveloxolone (RTA 408) 150 mg or placebo.

Extension: The extension will assess long-term safety and tolerability of omaveloxolone (RTA 408) in qualified participants with Friedreich's ataxia following completion of Part 1 or Part 2. Participants will not be unblinded to study treatment in Part 1 or Part 2 upon entering the extension study. Participants will receive open-label omaveloxolone (RTA 408) at 150 mg once daily.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Childrens Research Institute
• Austria
  • Innsbruck, Austria, 6020
    • Medical University Innsbruck
• Italy
  • Milan, Italy, 20133
    • Neurological Institute Carlo Besta
• United Kingdom
  • London, United Kingdom, WC1E 6BT
    • University College of London
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Neurology
    • Tampa, Florida, United States, 33612
      • USF Ataxia Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University Hospital - Neurology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Stead Family Children's Hospital
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Ohio State University - Neurology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have genetically confirmed Friedreich's ataxia
2. Have a modified FARS score ≥20 and ≤80
3. Be male or female and ≥16 years of age and ≤40 years of age
4. Have no changes to exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the 16-week study period
5. Have the ability to complete maximal exercise testing
6. Be able to swallow capsules

Exclusion Criteria:

1. Have uncontrolled diabetes (HbA1c >11.0%)
2. Have B-type natriuretic peptide value >200 pg/mL
3. Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease
4. Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
5. Have known or suspected active drug or alcohol abuse
6. Have clinically significant abnormalities of clinical hematology or biochemistry, including but not limited to elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase, or alanine aminotransferase
7. Have any abnormal laboratory test value or serious pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study enrollment

8. Have taken any of the following drugs within 7 days prior to Study Day 1 or plan to take any of these drugs during the time of study participation:

   1. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
   2. Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g., carbamazepine, phenytoin, ciprofloxacin, grapefruit juice)
   3. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
9. Have participated in any other interventional clinical study within 30 days prior to Study Day 1
10. Have a cognitive impairment that may preclude ability to comply with study procedures
11. Prior participation in a trial with omaveloxolone (RTA 408)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Omaveloxolone Capsules 2.5 and 5 mg; omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks	Drug: Omaveloxolone Capsules, 2.5 mg; Other Names: RTA 408 Capsules 2.5 mg; Drug: Omaveloxolone Capsules, 5 mg; Other Names: RTA 408 capsules, 5 mg
Experimental: Part 1 Omaveloxolone Capsules 10 mg; omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 10 mg; Other Names: RTA 408 capsules, 10 mg
Experimental: Part 1 Omaveloxolone Capsules 20 mg; Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 20 mg; Other Names: RTA 408 capsules, 20 mg
Experimental: Part 1 Omaveloxolone Capsules 40 mg; Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 40 mg; Other Names: RTA 408 capsules, 40 mg
Experimental: Part 1 Omaveloxolone Capsules 80 mg; Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 80 mg; Other Names: RTA 408 capsules, 80 mg
Experimental: Part 1 Omaveloxolone Capsules 160 mg; Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 160 mg; Other Names: RTA 408 capsules, 160 mg
Experimental: Part 1 Omaveloxolone Capsules 300 mg; Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks	Drug: Omaveloxolone Capsules, 300 mg; Other Names: RTA 408 capsules, 300 mg
Placebo Comparator: Part 1 Placebo Capsules; Placebo capsules administered orally once daily for 12 weeks	Drug: Placebo
Placebo Comparator: Part 2 Placebo Capsules; Placebo capsules administered orally once daily for 48 weeks	Drug: Placebo
Experimental: Part 2 Omaveloxolone Capsules 150 mg; Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks	Drug: Omaveloxolone Capsules, 150 mg; Other Names: RTA 408 capsules, 150 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Peak Work (in Watts/kg) During Exercise Testing at Week 12 in Part 1	Peak work attained during maximal exercise testing. Cycle ergometry using a recumbent stationary bicycle was used, and workload was increased incrementally. Peak work is defined as the workload at which patients reach maximal volition (defined as an inability to continue to exercise due to exhaustion).	Baseline through 12 weeks after participant receives the first dose in Part 1.
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48 in Part 2	The mFARS includes 4 of the 5 sections of the Friedreich's Ataxia Rating Scale (FARS): bulbar (score 0 to 11), upper limb coordination (score 0 to 36), lower limb coordination (score 0 to 16), and upright stability (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.	48 weeks after participant receives the first dose in Part 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1	The mFARS includes 4 of the 5 sections of the Friedreich's Ataxia Rating Scale (FARS): bulbar (score 0 to 11), upper limb coordination (score 0 to 36), lower limb coordination (score 0 to 16), and upright stability (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.	12 weeks after participant receives the first dose in Part 1

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: AbbVie; Friedreich's Ataxia Research Alliance

Publications and helpful links

General Publications

• Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, Boesch S, Nachbauer W, Mariotti C, Mathews KD, Giunti P, Wilmot G, Zesiewicz T, Perlman S, Goldsberry A, O'Grady M, Meyer CJ. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021 Feb;89(2):212-225. doi: 10.1002/ana.25934. Epub 2020 Nov 5.
• Lynch DR, Farmer J, Hauser L, Blair IA, Wang QQ, Mesaros C, Snyder N, Boesch S, Chin M, Delatycki MB, Giunti P, Goldsberry A, Hoyle C, McBride MG, Nachbauer W, O'Grady M, Perlman S, Subramony SH, Wilmot GR, Zesiewicz T, Meyer C. Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Ann Clin Transl Neurol. 2018 Nov 10;6(1):15-26. doi: 10.1002/acn3.660. eCollection 2019 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2015
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): December 19, 2025

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimated): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Oxidative Stress; RTA 408; RTA 408 Capsules; Mitochondrial dysfunction; omaveloxolone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Mitochondrial Diseases; Friedreich Ataxia; Substandard Drugs; Pharmaceutical Preparations; omaveloxolone; ORF 50 transactivator
• Other Study ID Numbers: RTA 408-C-1402; 2024-517436-22 (Other Identifier: EU CTIS Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No