RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02255435 |
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Recruitment Status :
Active, not recruiting
First Posted : October 2, 2014
Results First Posted : November 29, 2022
Last Update Posted : December 6, 2022
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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 patients 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 patients with Friedreich's ataxia.
This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone (RTA 408) in the treatment of patients 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 patients 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 patients with Friedreich's ataxia. Patients 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 patients with Friedreich's ataxia following completion of Part 1 or Part 2. Patients will not be unblinded to study treatment in Part 1 or Part 2 upon entering the extension study. Patients will receive open-label omaveloxolone (RTA 408) at 150 mg once daily.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Friedreich Ataxia | Drug: Omaveloxolone Capsules, 2.5 mg Drug: Omaveloxolone Capsules, 5 mg Drug: Omaveloxolone Capsules, 10 mg Drug: Placebo 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 | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 172 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe) |
| Study Start Date : | January 2015 |
| Actual Primary Completion Date : | October 31, 2019 |
| Estimated Study Completion Date : | December 2024 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: Omaveloxolone Capsules, 2.5 mg
Other Name: RTA 408 Capsules 2.5 mg Drug: Omaveloxolone Capsules, 5 mg Other Name: RTA 408 capsules, 5 mg |
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Experimental: Part 1 Omaveloxolone Capsules 10 mg
omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 10 mg
Other Name: RTA 408 capsules, 10 mg |
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Experimental: Part 1 Omaveloxolone Capsules 20 mg
Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 20 mg
Other Name: RTA 408 capsules, 20 mg |
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Experimental: Part 1 Omaveloxolone Capsules 40 mg
Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 40 mg
Other Name: RTA 408 capsules, 40 mg |
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Experimental: Part 1 Omaveloxolone Capsules 80 mg
Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 80 mg
Other Name: RTA 408 capsules, 80 mg |
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Experimental: Part 1 Omaveloxolone Capsules 160 mg
Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 160 mg
Other Name: RTA 408 capsules, 160 mg |
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Experimental: Part 1 Omaveloxolone Capsules 300 mg
Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks
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Drug: Omaveloxolone Capsules, 300 mg
Other Name: RTA 408 capsules, 300 mg |
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Placebo Comparator: Part 1 Placebo Capsules
Placebo capsules administered orally once daily for 12 weeks
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Drug: Placebo |
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Placebo Comparator: Part 2 Placebo Capsules
Placebo capsules administered orally once daily for 48 weeks
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Drug: Placebo |
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Experimental: Part 2 Omaveloxolone Capsules 150 mg
Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks
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Drug: Omaveloxolone Capsules, 150 mg
Other Name: RTA 408 capsules, 150 mg |
- Change From Baseline in Peak Work (in Watts/kg) During Exercise Testing at Week 12 in Part 1 [ Time Frame: Baseline through 12 weeks after participant receives the first dose 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).
- Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48 in Part 2 [ Time Frame: 48 weeks after participant receives the first dose 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.
- Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1 [ Time Frame: 12 weeks after participant receives the first dose 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.
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| Ages Eligible for Study: | 16 Years to 40 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
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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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255435
| United States, California | |
| UCLA | |
| Los Angeles, California, United States, 90095 | |
| United States, Florida | |
| University of Florida - Neurology | |
| Gainesville, Florida, United States, 32610 | |
| USF Ataxia Research Center | |
| Tampa, Florida, United States, 33612 | |
| United States, Georgia | |
| Emory University Hospital - Neurology | |
| Atlanta, Georgia, United States, 30329 | |
| United States, Iowa | |
| University of Iowa Stead Family Children's Hospital | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Ohio | |
| Ohio State University - Neurology | |
| Columbus, Ohio, United States, 43221 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Australia, Victoria | |
| Murdoch Childrens Research Institute | |
| Parkville, Victoria, Australia, 3052 | |
| Austria | |
| Medical University Innsbruck | |
| Innsbruck, Austria, 6020 | |
| Italy | |
| Neurological Institute Carlo Besta | |
| Milan, Italy, 20133 | |
| United Kingdom | |
| University College of London | |
| London, United Kingdom, WC1E 6BT | |
Documents provided by Reata Pharmaceuticals, Inc.:
| Responsible Party: | Reata Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT02255435 |
| Other Study ID Numbers: |
RTA 408-C-1402 |
| First Posted: | October 2, 2014 Key Record Dates |
| Results First Posted: | November 29, 2022 |
| Last Update Posted: | December 6, 2022 |
| Last Verified: | December 2022 |
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RTA 408 RTA 408 Capsules Oxidative Stress Mitochondrial dysfunction omaveloxolone |
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Ataxia Cerebellar Ataxia Friedreich Ataxia Dyskinesias Neurologic Manifestations Nervous System Diseases Cerebellar Diseases Brain Diseases |
Central Nervous System Diseases Spinocerebellar Degenerations Spinal Cord Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Mitochondrial Diseases Metabolic Diseases |