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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.

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 2, 2014
Last Update Posted Date March 4, 2019
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
Measure the change in the modified Friedreich's ataxia rating scale (FARS) [ Time Frame: 48 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2014)
Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT02255435 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
Measure the change of peak workload (in watts/kg) during exercise testing [ Time Frame: 48 weeks ]
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Friedreich Ataxia
Intervention  ICMJE
  • 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  ICMJE
  • 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, 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 26, 2017)
172
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2014)
52
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Italy,   United Kingdom,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT02255435
Other Study ID Numbers  ICMJE RTA 408-C-1402
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Reata Pharmaceuticals, Inc.
Study Sponsor  ICMJE Reata Pharmaceuticals, Inc.
Collaborators  ICMJE
  • AbbVie
  • Friedreich's Ataxia Research Alliance
Investigators  ICMJE Not Provided
PRS Account Reata Pharmaceuticals, Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP