A Study of Omaveloxolone in Children With Friedreich's Ataxia

Study Overview
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Brief Summary
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This is an open-label study evaluating the safety, tolerability, and PK following single-dose administration of omaveloxolone in pediatric patients with FA. The study will consist of 3 parts (Parts A, B, and C) based on age.

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

Official Title
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An Open-Label, Phase 1 Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of A Single-Dose Of Omaveloxolone In Children ≥2 To <16 Years Of Age With Friedreich's Ataxia

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Drug: Omaveloxolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have genetically confirmed FA. Be male or female and ≥2 years of age and <16 years of age. Have a left ventricular ejection fraction ≥ 40% (based on echocardiogram [ECHO] performed at Screening Visit). Be willing and able to cooperate with all aspects of the protocol. During screening, during the treatment period, and until 28 days following administration of the single dose of omaveloxolone, females of childbearing potential must practice at least 1 of the acceptable methods of birth control described in Section 6.9. During screening, during the treatment period, and until 28 days after the single dose of omaveloxolone, fertile males who have female partners of childbearing potential must practice one of the acceptable methods of birth control described in Section 6.9. Females of childbearing potential must have negative results for pregnancy tests at screening, based on a serum negative sample obtained prior to study drug administration. Parent or guardian willing to provide consent and patients ≥6 years of age willing to provide an assent form. Emancipated minor patients can provide consent. Exclusion Criteria: Have uncontrolled diabetes (HbA1c >11.0%). Have B-type natriuretic peptide (BNP) level >200 pg/mL at screening. Have a history of clinically significant (CS) left-sided heart disease and/or CS cardiac disease, with the exception of mild to moderate cardiomyopathy associated with FA. Presence of outflow tract obstruction defined as a peak instantaneous gradient >50 mmHg (based off ECHO performed at screening). Have a known active fungal, bacterial, and/or viral infection, including HIV or hepatitis (B or C). Have known or suspected active drug, nicotine use, or alcohol abuse, as per investigator judgment. Have any abnormal laboratory test value or CS pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study participation. Have taken any moderate or strong inhibitors and/or inducers of cytochrome P450 3A4 within the 7 days prior to Day 1 or plan to take during study participation (eg, itraconazole, carbamazepine, phenytoin, ciprofloxacin, grapefruit juice,cannabidiol, fluconazole, fluvoxamine, verapamil, diltiazem). Have a history of CS liver disease (eg, fibrosis, cirrhosis, hepatitis), or have clinically relevant deviations in laboratory tests at screening Plan to or have participated in any other interventional clinical study within the 30 days prior to Day 1. Have a cognitive impairment that may preclude ability to comply with study procedures, in the opinion of the investigator. Be unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator. Have previously documented mitochondrial respiratory chain disease. Have a history of thromboembolic events within the past 5 years. Plan to or have taken anticoagulant therapy within 30 days prior to Day 1 with the exception of a daily low dose aspirin (up to 81 mg). Plan to or have scheduled surgical treatment for scoliosis or foot deformity during the study. Have had significant suicidal ideation within 30 days prior to Screening Visit, as per investigator judgment, or any history of suicide attempt. For females, be pregnant or breastfeeding. Positive test result for COVID-19 at screening.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Cohort 1<br>Part A - Cohort 1 will contain patients ≥12 to <16 years of age. Patients will receive a single oral dose of 150 mg omaveloxolone. | Drug: Omaveloxolone<br>* One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.<br>* Other names: Skyclarys;|
| Experimental: Part A - Cohort 2<br>Part A - Cohort 2 will contain patients ≥12 to <16 years of age. Patients will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A - Cohort 1 to select the dose. | Drug: Omaveloxolone<br>* One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.<br>* Other names: Skyclarys;|
| Experimental: Part B<br>Part B will contain patients ≥6 to <12 years of age and will initiate in parallel with Part A - Cohort 2. Patients will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A - Cohort 1 to select the dose. | Drug: Omaveloxolone<br>* One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.<br>* Other names: Skyclarys;|
| Experimental: Part C<br>Part C will contain patients ≥2 to <6 years of age. Subjects will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A and Part B to select the dose. | Drug: Omaveloxolone<br>* One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.<br>* Other names: Skyclarys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent clearance (CL/F) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 
| Maximum concentration (Cmax) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 
| Volume of distribution (V/F) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 
| Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 
| Area under the plasma concentration-time curve from 0 to tlast (AUC0-tlas) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 
| Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) of omaveloxolone | Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C). | Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Friedreich's ataxia, FA, RTA 408, Omaveloxolone