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

• ClinicalTrials.gov Identifier: NCT02255435
• Recruitment Status: Active, not recruiting
• First Posted: October 2, 2014
• Last Update Posted: March 24, 2022
• Sponsor: Reata Pharmaceuticals, Inc.
• Collaborators: AbbVie; Friedreich's Ataxia Research Alliance
• Information provided by (Responsible Party): Reata Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: September 30, 2014
• First Posted Date: October 2, 2014
• Last Update Posted Date: March 24, 2022
• Study Start Date: January 2015
• Actual Primary Completion Date: October 3, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 28, 2019): Measure the change in the modified Friedreich's ataxia rating scale (FARS) [ Time Frame: 48 weeks ]
• Original Primary Outcome Measures (submitted: September 30, 2014): Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 12 weeks ]
• Current Secondary Outcome Measures (submitted: February 28, 2019): Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 48 weeks ]
• Original Secondary Outcome Measures (submitted: September 30, 2014): Measure the change in the modified Friedreich's ataxia rating scale (FARS) [ Time Frame: 12 weeks ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe
• Official Title: A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe)

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Friedreich Ataxia

Intervention

• 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
• Drug: Omaveloxolone Capsules, 10 mg
  Other Name: RTA 408 capsules, 10 mg
• Drug: Placebo
• Drug: Omaveloxolone Capsules, 20 mg
  Other Name: RTA 408 capsules, 20 mg
• Drug: Omaveloxolone Capsules, 40 mg
  Other Name: RTA 408 capsules, 40 mg
• Drug: Omaveloxolone Capsules, 80 mg
  Other Name: RTA 408 capsules, 48 mg
• Drug: Omaveloxolone Capsules, 160 mg
  Other Name: RTA 408 capsules, 160 mg
• Drug: Omaveloxolone Capsules, 300 mg
  Other Name: RTA 408 capsules, 300 mg
• Drug: Omaveloxolone Capsules, 150 mg
  Other Name: RTA 408 capsules, 150 mg

Study Arms

• 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
  Interventions:

  • Drug: Omaveloxolone Capsules, 2.5 mg
  • Drug: Omaveloxolone Capsules, 5 mg
• Experimental: Omaveloxolone Capsules 10 mg
  omaveloxolone (RTA 408) Capsules, 10 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 10 mg
• Placebo Comparator: Placebo Capsules
  Placebo capsules taken orally once daily for 12 weeks
  Intervention: Drug: Placebo
• Experimental: Omaveloxolone Capsules 20 mg
  omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 20 mg
• Experimental: Omaveloxolone Capsules 40 mg
  omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 40 mg
• Experimental: Omaveloxolone Capsules 80 mg
  omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 80 mg
• Experimental: Omaveloxolone Capsules 160 mg
  omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 160 mg
• Experimental: Omaveloxolone Capsules 300 mg
  omaveloxolone (RTA 408) Capsules, 300 mg taken orally once daily for 12 weeks
  Intervention: Drug: Omaveloxolone Capsules, 300 mg
• Experimental: Omaveloxolone Capsules 150 mg
  omaveloxolone (RTA 408) Capsules, 150 mg taken orally once daily for 24 weeks
  Intervention: Drug: Omaveloxolone Capsules, 150 mg

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 26, 2017): 172
• Original Estimated Enrollment (submitted: September 30, 2014): 52
• Estimated Study Completion Date: December 2022
• Actual Primary Completion Date: October 3, 2019 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 40 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Italy, United Kingdom, United States
• Removed Location Countries: Brazil

Administrative Information

• NCT Number: NCT02255435
• Other Study ID Numbers: RTA 408-C-1402
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Reata Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Reata Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current

Collaborators

• AbbVie
• Friedreich's Ataxia Research Alliance

• Investigators: Not Provided
• PRS Account: Reata Pharmaceuticals, Inc.
• Verification Date: March 2022