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RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe

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ClinicalTrials.gov Identifier: NCT02255435
Recruitment Status : Active, not recruiting
First Posted : October 2, 2014
Last Update Posted : March 4, 2019
Sponsor:
Collaborators:
AbbVie
Friedreich's Ataxia Research Alliance
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Study Description
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Brief Summary:

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 Design
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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
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Omaveloxolone Capsules 2.5 and 5 mg
omaveloxolone (RTA 408) Capsules, 2.5 mg taken orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks
 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
Experimental: Omaveloxolone Capsules 10 mg
omaveloxolone (RTA 408) Capsules, 10 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 10 mg
Other Name: RTA 408 capsules, 10 mg
Placebo Comparator: Placebo Capsules
Placebo capsules taken orally once daily for 12 weeks
 Drug: Placebo
Experimental: Omaveloxolone Capsules 20 mg
omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 20 mg
Other Name: RTA 408 capsules, 20 mg
Experimental: Omaveloxolone Capsules 40 mg
omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 40 mg
Other Name: RTA 408 capsules, 40 mg
Experimental: Omaveloxolone Capsules 80 mg
omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 80 mg
Other Name: RTA 408 capsules, 48 mg
Experimental: Omaveloxolone Capsules 160 mg
omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 160 mg
Other Name: RTA 408 capsules, 160 mg
Experimental: Omaveloxolone Capsules 300 mg
omaveloxolone (RTA 408) Capsules, 300 mg taken orally once daily for 12 weeks
 Drug: Omaveloxolone Capsules, 300 mg
Other Name: RTA 408 capsules, 300 mg
Experimental: Omaveloxolone Capsules 150 mg
omaveloxolone (RTA 408) Capsules, 150 mg taken orally once daily for 24 weeks
 Drug: Omaveloxolone Capsules, 150 mg
Other Name: RTA 408 capsules, 150 mg


Outcome Measures
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Primary Outcome Measures :
  1. Measure the change in the modified Friedreich's ataxia rating scale (FARS) [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 48 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   16 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
AbbVie
Friedreich's Ataxia Research Alliance
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02255435     History of Changes
Other Study ID Numbers: RTA 408-C-1402
First Posted: October 2, 2014    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019

Keywords provided by Reata Pharmaceuticals, Inc.:
RTA 408
RTA 408 Capsules
Oxidative Stress
Mitochondrial dysfunction
omaveloxolone

Additional relevant MeSH terms:
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Ataxia
Cerebellar Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
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