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

Primary Purpose

Friedreich Ataxia

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
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
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Friedreich Ataxia focused on measuring RTA 408, RTA 408 Capsules, Oxidative Stress, Mitochondrial dysfunction, omaveloxolone

Eligibility Criteria

16 Years - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • UCLA
  • University of Florida - Neurology
  • USF Ataxia Research Center
  • Emory University Hospital - Neurology
  • University of Iowa Stead Family Children's Hospital
  • Ohio State University - Neurology
  • Children's Hospital of Philadelphia
  • Murdoch Childrens Research Institute
  • Medical University Innsbruck
  • Neurological Institute Carlo Besta
  • University College of London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Experimental

Arm Label

Part 1 Omaveloxolone Capsules 2.5 and 5 mg

Part 1 Omaveloxolone Capsules 10 mg

Part 1 Omaveloxolone Capsules 20 mg

Part 1 Omaveloxolone Capsules 40 mg

Part 1 Omaveloxolone Capsules 80 mg

Part 1 Omaveloxolone Capsules 160 mg

Part 1 Omaveloxolone Capsules 300 mg

Part 1 Placebo Capsules

Part 2 Placebo Capsules

Part 2 Omaveloxolone Capsules 150 mg

Arm Description

omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks

omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks

Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks

Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks

Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks

Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks

Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks

Placebo capsules administered orally once daily for 12 weeks

Placebo capsules administered orally once daily for 48 weeks

Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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.

Full Information

First Posted
September 30, 2014
Last Updated
October 11, 2023
Sponsor
Biogen
Collaborators
AbbVie, Friedreich's Ataxia Research Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT02255435
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 31, 2015 (Actual)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
Collaborators
AbbVie, Friedreich's Ataxia Research Alliance

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
This study was previously posted by Reata Pharmaceuticals. In September 2023, sponsorship of the trial was transferred to Biogen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich Ataxia
Keywords
RTA 408, RTA 408 Capsules, Oxidative Stress, Mitochondrial dysfunction, omaveloxolone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
172 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 Omaveloxolone Capsules 2.5 and 5 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks
Arm Title
Part 1 Omaveloxolone Capsules 10 mg
Arm Type
Experimental
Arm Description
omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Omaveloxolone Capsules 20 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Omaveloxolone Capsules 40 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Omaveloxolone Capsules 80 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Omaveloxolone Capsules 160 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Omaveloxolone Capsules 300 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks
Arm Title
Part 1 Placebo Capsules
Arm Type
Placebo Comparator
Arm Description
Placebo capsules administered orally once daily for 12 weeks
Arm Title
Part 2 Placebo Capsules
Arm Type
Placebo Comparator
Arm Description
Placebo capsules administered orally once daily for 48 weeks
Arm Title
Part 2 Omaveloxolone Capsules 150 mg
Arm Type
Experimental
Arm Description
Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 2.5 mg
Other Intervention Name(s)
RTA 408 Capsules 2.5 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 5 mg
Other Intervention Name(s)
RTA 408 capsules, 5 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 10 mg
Other Intervention Name(s)
RTA 408 capsules, 10 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 20 mg
Other Intervention Name(s)
RTA 408 capsules, 20 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 40 mg
Other Intervention Name(s)
RTA 408 capsules, 40 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 80 mg
Other Intervention Name(s)
RTA 408 capsules, 80 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 160 mg
Other Intervention Name(s)
RTA 408 capsules, 160 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 300 mg
Other Intervention Name(s)
RTA 408 capsules, 300 mg
Intervention Type
Drug
Intervention Name(s)
Omaveloxolone Capsules, 150 mg
Other Intervention Name(s)
RTA 408 capsules, 150 mg
Primary Outcome Measure Information:
Title
Change From Baseline in Peak Work (in Watts/kg) During Exercise Testing at Week 12 in Part 1
Description
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).
Time Frame
Baseline through 12 weeks after participant receives the first dose in Part 1.
Title
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48 in Part 2
Description
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.
Time Frame
48 weeks after participant receives the first dose in Part 2
Secondary Outcome Measure Information:
Title
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1
Description
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.
Time Frame
12 weeks after participant receives the first dose in Part 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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)
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Florida - Neurology
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
USF Ataxia Research Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University Hospital - Neurology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
University of Iowa Stead Family Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Ohio State University - Neurology
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Murdoch Childrens Research Institute
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Medical University Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Neurological Institute Carlo Besta
City
Milan
ZIP/Postal Code
20133
Country
Italy
Facility Name
University College of London
City
London
ZIP/Postal Code
WC1E 6BT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Citations:
PubMed Identifier
33068037
Citation
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. Erratum In: Ann Neurol. 2023 Oct 5;:
Results Reference
derived
PubMed Identifier
30656180
Citation
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.
Results Reference
derived

Learn more about this trial

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

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