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

NCT02255435 | Completed Phase 2 Results DMC

• 2 other identifiers: RTA 408-C-14022024-517436-22
• Study Type: interventional
• Target: 172
• Locations: 4 countries
• Sites: 10

Brief Summary

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.

Conditions

Friedreich Ataxia

Keywords

RTA 408; RTA 408 Capsules; Oxidative Stress; Mitochondrial dysfunction; omaveloxolone

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1

  12 weeks after participant receives the first dose in Part 1

Study Arms (10)

Part 1 Omaveloxolone Capsules 2.5 and 5 mg

EXPERIMENTAL

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; Drug: Omaveloxolone Capsules, 5 mg

Part 1 Omaveloxolone Capsules 10 mg

EXPERIMENTAL

omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 10 mg

Part 1 Omaveloxolone Capsules 20 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 20 mg

Part 1 Omaveloxolone Capsules 40 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 40 mg

Part 1 Omaveloxolone Capsules 80 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 80 mg

Part 1 Omaveloxolone Capsules 160 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 160 mg

Part 1 Omaveloxolone Capsules 300 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks

Drug: Omaveloxolone Capsules, 300 mg

Part 1 Placebo Capsules

PLACEBO COMPARATOR

Placebo capsules administered orally once daily for 12 weeks

Drug: Placebo

Part 2 Placebo Capsules

PLACEBO COMPARATOR

Placebo capsules administered orally once daily for 48 weeks

Drug: Placebo

Part 2 Omaveloxolone Capsules 150 mg

EXPERIMENTAL

Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks

Drug: Omaveloxolone Capsules, 150 mg

Interventions

Omaveloxolone Capsules, 2.5 mg DRUG

Also known as: RTA 408 Capsules 2.5 mg

Part 1 Omaveloxolone Capsules 2.5 and 5 mg

Omaveloxolone Capsules, 5 mg DRUG

Also known as: RTA 408 capsules, 5 mg

Part 1 Omaveloxolone Capsules 2.5 and 5 mg

Omaveloxolone Capsules, 10 mg DRUG

Also known as: RTA 408 capsules, 10 mg

Part 1 Omaveloxolone Capsules 10 mg

Placebo DRUG

Part 1 Placebo Capsules; Part 2 Placebo Capsules

Omaveloxolone Capsules, 20 mg DRUG

Also known as: RTA 408 capsules, 20 mg

Part 1 Omaveloxolone Capsules 20 mg

Omaveloxolone Capsules, 40 mg DRUG

Also known as: RTA 408 capsules, 40 mg

Part 1 Omaveloxolone Capsules 40 mg

Omaveloxolone Capsules, 80 mg DRUG

Also known as: RTA 408 capsules, 80 mg

Part 1 Omaveloxolone Capsules 80 mg

Omaveloxolone Capsules, 160 mg DRUG

Also known as: RTA 408 capsules, 160 mg

Part 1 Omaveloxolone Capsules 160 mg

Omaveloxolone Capsules, 300 mg DRUG

Also known as: RTA 408 capsules, 300 mg

Part 1 Omaveloxolone Capsules 300 mg

Omaveloxolone Capsules, 150 mg DRUG

Also known as: RTA 408 capsules, 150 mg

Part 2 Omaveloxolone Capsules 150 mg

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Have genetically confirmed Friedreich's ataxia
• Have a modified FARS score ≥20 and ≤80
• Be male or female and ≥16 years of age and ≤40 years of age
• 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
• Have the ability to complete maximal exercise testing
• Be able to swallow capsules

You may not qualify if:

• Have uncontrolled diabetes (HbA1c \>11.0%)
• Have B-type natriuretic peptide value \>200 pg/mL
• Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease
• Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
• Have known or suspected active drug or alcohol abuse
• 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
• 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
• 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:
• Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
• Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g., carbamazepine, phenytoin, ciprofloxacin, grapefruit juice)
• Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
• Have participated in any other interventional clinical study within 30 days prior to Study Day 1
• Have a cognitive impairment that may preclude ability to comply with study procedures
• Prior participation in a trial with omaveloxolone (RTA 408)

Sponsors & Collaborators

• Biogen: lead
• AbbVie: collaborator
• Friedreich's Ataxia Research Alliance: collaborator

Study Sites (11)

UCLA

Los Angeles, California, 90095, United States

Location

University of Florida - Neurology

Gainesville, Florida, 32610, United States

Location

USF Ataxia Research Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital - Neurology

Atlanta, Georgia, 30329, United States

Location

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Ohio State University - Neurology

Columbus, Ohio, 43221, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Murdoch Childrens Research Institute

Parkville, Victoria, 3052, Australia

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

Neurological Institute Carlo Besta

Milan, 20133, Italy

Location

University College of London

London, WC1E 6BT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33068037 DERIVED

• 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.

  PMID: 30656180 DERIVED

MeSH Terms

Conditions

Friedreich Ataxia; Mitochondrial Diseases

Interventions

omaveloxolone; ORF 50 transactivator

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; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Study Start: January 31, 2015
• Primary Completion: October 31, 2019
• Study Completion: December 19, 2025
• Last Updated: January 23, 2026
• Results First Posted: November 29, 2022

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); AU (1); IT (1); US (7)