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

Friedreich Ataxia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02255435
• Other study ID #: RTA 408-C-1402
• Secondary ID: 2015-002762-23
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 31, 2015
• Est. completion date: December 1, 2024

Study information

• Verified date: May 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Description:

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 172
• Est. completion date: December 1, 2024
• Est. primary completion date: October 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia

Intervention

Drug:
• Omaveloxolone Capsules, 2.5 mg

• Omaveloxolone Capsules, 5 mg

• Omaveloxolone Capsules, 10 mg

• Placebo

• Omaveloxolone Capsules, 20 mg

• Omaveloxolone Capsules, 40 mg

• Omaveloxolone Capsules, 80 mg

• Omaveloxolone Capsules, 160 mg

• Omaveloxolone Capsules, 300 mg

• Omaveloxolone Capsules, 150 mg

Locations

Country	Name	City	State
Australia	Murdoch Childrens Research Institute	Parkville	Victoria
Austria	Medical University Innsbruck	Innsbruck
Italy	Neurological Institute Carlo Besta	Milan
United Kingdom	University College of London	London
United States	Emory University Hospital - Neurology	Atlanta	Georgia
United States	Ohio State University - Neurology	Columbus	Ohio
United States	University of Florida - Neurology	Gainesville	Florida
United States	University of Iowa Stead Family Children's Hospital	Iowa City	Iowa
United States	UCLA	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	USF Ataxia Research Center	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Reata, a wholly owned subsidiary of Biogen	AbbVie, Friedreich's Ataxia Research Alliance

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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