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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02255435




Registration number
NCT02255435
Ethics application status
Date submitted
30/09/2014
Date registered
2/10/2014
Date last updated
7/06/2024

Titles & IDs
Public title
RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe
Scientific title
A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe)
Secondary ID [1] 0 0
2015-002762-23
Secondary ID [2] 0 0
RTA 408-C-1402
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Friedreich Ataxia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Omaveloxolone Capsules, 2.5 mg
Treatment: Drugs - Omaveloxolone Capsules, 5 mg
Treatment: Drugs - Omaveloxolone Capsules, 10 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Omaveloxolone Capsules, 20 mg
Treatment: Drugs - Omaveloxolone Capsules, 40 mg
Treatment: Drugs - Omaveloxolone Capsules, 80 mg
Treatment: Drugs - Omaveloxolone Capsules, 160 mg
Treatment: Drugs - Omaveloxolone Capsules, 300 mg
Treatment: Drugs - Omaveloxolone Capsules, 150 mg

Experimental: Part 1 Omaveloxolone Capsules 2.5 and 5 mg - omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks

Experimental: Part 1 Omaveloxolone Capsules 10 mg - omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks

Experimental: Part 1 Omaveloxolone Capsules 20 mg - Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks

Experimental: Part 1 Omaveloxolone Capsules 40 mg - Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks

Experimental: Part 1 Omaveloxolone Capsules 80 mg - Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks

Experimental: Part 1 Omaveloxolone Capsules 160 mg - Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks

Experimental: Part 1 Omaveloxolone Capsules 300 mg - Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks

Placebo Comparator: Part 1 Placebo Capsules - Placebo capsules administered orally once daily for 12 weeks

Placebo Comparator: Part 2 Placebo Capsules - Placebo capsules administered orally once daily for 48 weeks

Experimental: Part 2 Omaveloxolone Capsules 150 mg - Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks


Treatment: Drugs: Omaveloxolone Capsules, 2.5 mg


Treatment: Drugs: Omaveloxolone Capsules, 5 mg


Treatment: Drugs: Omaveloxolone Capsules, 10 mg


Treatment: Drugs: Placebo


Treatment: Drugs: Omaveloxolone Capsules, 20 mg


Treatment: Drugs: Omaveloxolone Capsules, 40 mg


Treatment: Drugs: Omaveloxolone Capsules, 80 mg


Treatment: Drugs: Omaveloxolone Capsules, 160 mg


Treatment: Drugs: Omaveloxolone Capsules, 300 mg


Treatment: Drugs: Omaveloxolone Capsules, 150 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Peak Work (in Watts/kg) During Exercise Testing at Week 12 in Part 1
Timepoint [1] 0 0
Baseline through 12 weeks after participant receives the first dose in Part 1.
Primary outcome [2] 0 0
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48 in Part 2
Timepoint [2] 0 0
48 weeks after participant receives the first dose in Part 2
Secondary outcome [1] 0 0
Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1
Timepoint [1] 0 0
12 weeks after participant receives the first dose in Part 1

Eligibility
Key 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
Minimum age
16 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
172
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Childrens Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
Austria
State/province [7] 0 0
Innsbruck
Country [8] 0 0
Italy
State/province [8] 0 0
Milan
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Reata, a wholly owned subsidiary of Biogen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Friedreich's Ataxia Research Alliance
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02255435
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02255435