Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Omaveloxolone · 16 trials · 13 indications
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
The mFARS is a validated and sensitive rating scale that was developed to quantitatively assess the severity of the neurologic features of FA in adults and adolescents. Scores on the mFARS range from 0 to 93, with lower scores indicating better neurological function. The subscales of the mFARS assessment and maximum score for each subscale are: bulbar function (Subscale A; 2 assessments of speech and cough; maximum score = 5), upper limb coordination (Subscale B; 5 assessments of coordination of movement and function in arms and hands with each limb scored individually; maximum score = 36), lower limb coordination (Subscale C; 2 assessments of coordination of movement and function of lower limbs with each limb scored individually; maximum score = 16), and upright stability (USS, Subscale E; 9 assessments of sitting posture, stance, tandem walk, and gait assessments; maximum score = 36).
The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment of individuals ≥ 6 years of age. The C-SSRS is a clinical interview providing a summary of both ideation and behavior that can be administered by the clinician during any evaluation or risk assessment to identify the level and type of suicidality present. The assessment includes "yes" or "no" responses for 5 questions each, related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation, from 1 to 5, with 5 being the most severe.
Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.
Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected at baseline for all participants and will be stopped once the participant reaches Tanner Stage 5 in all gender-appropriate scales.
Cycle ergometry using a stationary recumbent bike was used to conduct maximal exercise testing. 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 of peak workload during exercise testing was measured at baseline, Week 4, and Week 12. Change from baseline at Week 12 reported.
Cycle ergometry using a recumbent stationary bicycle was used to conduct maximal exercise testing and workload was increased incrementally. Peak work is defined as the workload at which participants reach maximal volition (defined as an inability to continue to exercise due to exhaustion). A positive change from baseline suggests an improvement.
An adverse event (AE) was any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as any AEs, regardless of relationship to study drug, that had an onset or worsened in severity on or after the first dose of study drug.
The Friedreich Ataxia Rating Scale (FARS) is a neurological-exam-based rating scale with five sections: Bulbar (section A), Upper Limb Coordination (section B), Lower Limb Coordination (section C), Peripheral Nervous System (section D), and Upright Stability (section E). mFARS is the sum of sections A (score 0 to 11), B (score 0 to 36), C (score 0 to 16), and E (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.
An AE was any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as any AEs, regardless of relationship to study drug, that had an onset or worsened in severity on or after the first dose of study drug.
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose results in death, in the view of investigator, places the participant at immediate risk of death (life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect or is medically important event.
Vital signs, including blood pressure (BP), heart rate (HR), and oral body temperature, will be assessed.
The relationship between ∆QTcF and omaveloxolone and its metabolites, M17 and M22 plasma concentrations will be investigated by a linear mixed effects modeling approach with ∆ QTcF as the dependent variable, time-matched concentration of omaveloxolone and its metabolites as a continuous covariate (ie, 0 for placebo), and centered baseline QTcF as an additional covariate, treatment (active = 1; or placebo = 0) and time as categorical factors, and a random intercept and slope per subject.
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points over a 336-hour period following each omaveloxolone dose for the duration of the study.
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points over a 336-hour period following each omaveloxolone dose for the duration of the study.
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points over a 336-hour period following each omaveloxolone dose for the duration of the study.
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine area under the curve (AUC).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
Mass balance and metabolite profiles will be assessed by blood sampling for omaveloxolone to determine maximum concentration of total radioactivity
Mass balance and metabolite profiles will be assessed by blood sampling for total radioactivity to determine area under the concentration-time curve.
Rates and routes of elimination will be assessed by urine sampling for radioactivity.
Rates and routes of elimination will be assessed by sampling of feces for radioactivity.
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under curve (AUC).
Best overall response rate (ORR) is defined as the proportion of patients with complete or partial tumor size reduction according to RECIST v1.1 criteria. Stable disease is not a component of ORR. Complete response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial reduction: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The first occurrence of a response is considered an unconfirmed response. A CR or PR which persists to the next tumor burden assessment is then considered a confirmed response. Confirmed plus unconfirmed best overall response are presented. A subject may be counted twice if best unconfirmed response and best confirmed response are different.
To determine the recommended Phase 2 dose of RTA 408 following oral administration to patients with metastatic or incurable NSCLC or melanoma that is relapsed, refractory after standard of care therapy, or for which standard of care therapy is not appropriate.
| Arm | Type | Description |
|---|---|---|
| Part 1: Omaveloxolone | EXPERIMENTAL | Participants will receive a single oral dose of omaveloxolone once a day (QD) for up to 52 weeks in Part 1 of the study. |
| Part 1: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo, orally, QD for up to 52 weeks in Part 1 of the study. |
| Part 2A Continued Efficacy Evaluation: Omaveloxolone | EXPERIMENTAL | Participants will receive a single oral dose of omaveloxolone, QD for up to 104 weeks in Part 2A of the study. |
| Part 2B Safety: Omaveloxolone | EXPERIMENTAL | Participants will receive a single oral dose of open-label omaveloxolone, QD for up to 104 weeks in Part 2B of the study. |
| omaveloxolone Capsules 2.5 mg and 5 mg | EXPERIMENTAL | omaveloxolone (RTA 408) Capsules, 2.5 mg taken orally once daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks |
| omaveloxolone Capsules 10 mg | EXPERIMENTAL | omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 12 weeks |
| Placebo Capsules | PLACEBO_COMPARATOR | Placebo capsules taken orally once daily for 12 weeks |
| omaveloxolone Capsules 20 mg | EXPERIMENTAL | omaveloxolone (RTA 408) Capsules, 20 mg taken orally once daily for 12 weeks. |
| omaveloxolone Capsules 40 mg | EXPERIMENTAL | omaveloxolone (RTA 408) Capsules, 40 mg taken orally once daily for 12 weeks. |
| omaveloxolone Capsules 80 mg | EXPERIMENTAL | omaveloxolone (RTA 408) Capsules, 80 mg taken orally once daily for 12 weeks. |
| omaveloxolone Capsules 160 mg | EXPERIMENTAL | omaveloxolone (RTA 408) Capsules, 160 mg taken orally once daily for 12 weeks. |
| Part 1: Omaveloxolone 2.5 and 5 mg | EXPERIMENTAL | Participants received omaveloxolone 2.5 mg, oral capsule, QD for 2 weeks, followed by 5 mg Omaveloxolone, oral capsule, QD for 10 weeks. |
| Part 1: Omaveloxolone 10 mg | EXPERIMENTAL | Participants received omaveloxolone 10 mg, oral capsule, QD for 12 weeks. |
| Part 1: Omaveloxolone 20 mg | EXPERIMENTAL | Participants received omaveloxolone 20 mg, oral capsule, QD for 12 weeks. |
| Part 1: Omaveloxolone 40 mg | EXPERIMENTAL | Participants received omaveloxolone 40 mg, oral capsule, QD for 12 weeks. |
| Part 1: Omaveloxolone 80 mg | EXPERIMENTAL | Participants received omaveloxolone 80 mg, oral capsule, QD for 12 weeks. |
| Part 1: Omaveloxolone 160 mg | EXPERIMENTAL | Participants received omaveloxolone 160 mg, oral capsule, QD for 12 weeks. |
| Part 1: Omaveloxolone 300 mg | EXPERIMENTAL | Participants received omaveloxolone 300 mg, oral capsule, QD for 12 weeks. |
| Part 2: Omaveloxolone 150 mg | EXPERIMENTAL | Participants received omaveloxolone 150 mg, oral capsule, QD for 48 weeks. |
| Part 2: Placebo | PLACEBO_COMPARATOR | Participants received placebo, oral capsule, QD for 48 weeks. |
| OLE: Placebo/ Omaveloxolone | EXPERIMENTAL | All eligible participants who had received either omaveloxone or placebo in Part 1 and eligible participants who received placebo in Part 2 received omaveloxone, 150 mg, oral capsule, QD, until the drug was available through commercial channels or alternate post-trial access mechanisms, or until participant withdrawal, whichever was sooner (up to approximately 370 weeks). |
| OLE: Omaveloxolone/ Omaveloxolone | EXPERIMENTAL | All eligible participants who had received omaveloxone in Part 2 continued to receive omaveloxolone, 150 mg, oral capsule, QD until the drug was available through commercial channels or alternate post-trial access mechanisms, or until participant withdrawal, whichever was sooner (up to approximately 370 weeks). |
| Treatment Sequence AB | EXPERIMENTAL | Participants will receive treatment A (omaveloxolone capsule orally) on Day 1 followed by treatment B (omaveloxolone TOS) on Day 15. |
| Treatment Sequence BA | EXPERIMENTAL | Participants will receive treatment B (omaveloxolone TOS) on Day 1 followed by treatment A (omaveloxolone capsule orally) on Day 15. |
| Period 1: Omeprazole | EXPERIMENTAL | Participants will receive a single oral dose of omeprazole on Day 1. |
| Period 2: Omaveloxolone + Omeprazole | EXPERIMENTAL | Participants will receive omaveloxolone from Days 2 to 15, followed by both omaveloxolone and omeprazole on Day 16. |
| Omaveloxolone | EXPERIMENTAL | Participants will receive a single oral dose of omaveloxolone on Day 1. |
| Part 1 and 2: Cohort A1 | EXPERIMENTAL | Cohort A1 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, 150 milligrams (mg), capsule, on Day 1 of the treatment period of part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian population pharmacokinetics (popPK) analyses. |
| Part 1 and 2: Cohort A2 | EXPERIMENTAL | Cohort A2 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Part 1 and 2: Cohort B1 | EXPERIMENTAL | Cohort B1 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A2. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohort A1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Part 1 and 2: Cohort C1 | EXPERIMENTAL | Cohort C1 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Part 1 and 2: Cohort A3 | EXPERIMENTAL | Cohort A3 will contain participants 12 to \<16 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Part 1 and 2: Cohort B2 | EXPERIMENTAL | Cohort B2 will contain participants 7 to \<12 years of age and will initiate in parallel with Cohort A3. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from cohorts A1, A2, and B1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Part 1 and 2: Cohort C2 | EXPERIMENTAL | Cohort C2 will contain participants 2 to \<7 years of age. Participants will receive a single oral dose of omaveloxolone, capsule, at a dosage level determined by a Bayesian popPK analysis using the data from Cohorts A1, A2, A3, B1, B2, and C1 to select the dose in part 1, followed by the same dose in part 2 up to when the last participant enrolled has the opportunity for their week 240. The dose in part 2 may be adjusted as per additional safety and Bayesian popPK analyses. |
| Sequence ABC | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1 - 15), Treatment B (Period 2 from Day 15 - 29), and Treatment C(Period 3 from Day 29 -32) |
| Sequence BAC | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1-15), Treatment A (Period 2 from Day 15 - 29, and Treatment C (Period 3 from Day 29 to 32) |
| Sequence ACB | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1-15), Treatment C (Period 2 from Day 15 -18), and Treatment B (Period 3from Day 18 - 32) |
| Sequence BCA | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1 - 15), Treatment C (Period 2 from Day 15 to 18), and Treatment A (Period 3 from Day 18 - 32) |
| Sequence CAB | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment A (Period 2 from Day 4 - 18), and Treatment B (Period 3 from Day 18 - 32) |
| Sequence CBA | EXPERIMENTAL | Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment B (Period 2 from Day 4 - 18), and Treatment A (Period 3 from Day 18 - 32) |
| Omaveloxolone only (Period 1), Then Omaveloxolone and efavirenz (Period 2) | EXPERIMENTAL | Period 1 (Day 1 - 15): Omaveloxolone Capsules, 150 mg, administered orally in a single dose on Day 1 Period 2 (Day 15 - 43): Efavirenz Tablet, 600 mg, administered orally once daily from Day 15 - Day 42 and Omaveloxolone Capsules, 150 mg, administered orally in a single dose on Day 29 |
| Group 1: matched healthy subjects | EXPERIMENTAL | On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose. |
| Group 2: subjects with mild hepatic impairment | EXPERIMENTAL | On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose. |
| Group 3: subjects with moderate hepatic impairment | EXPERIMENTAL | On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose. |
| Group 4: subjects with severe hepatic impairment | EXPERIMENTAL | On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose. |
| Omaveloxolone and Multiple Drugs (Part 1) | EXPERIMENTAL | Single oral doses of 2 mg midazolam, 1 mg repaglinide, 500 mg metformin, and a 10 mg rosuvastatin/0.25 mg digoxin cocktail on Days 1, 2, 3, and 5, respectively, and 18, 19, 20, and 22, respectively. Oral doses of 150 mg omaveloxolone on Days 12 to 27 |
| Omaveloxolone & Gemfibrozil (Part 2) | EXPERIMENTAL | Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 600 mg gemfibrozil (twice daily) on Days 10 to 18 |
| Omaveloxolone and Itraconazole (Part 3) | EXPERIMENTAL | Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 200 mg itraconazole on Days 10 to 18. |
| Omaveloxolone and Verapamil (Part 4) | EXPERIMENTAL | Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 120 mg verapamil on Days 10 to 18. |
| Healthy Male Subjects | EXPERIMENTAL | Single oral dose of 150 mg of \[14C\] omaveloxolone containing approximately 90 μCi as a capsule after an overnight fast of at least 10 hours. |
| Food Effect (Fasted) | EXPERIMENTAL | Subjects will be randomly assigned to one of the two treatment sequences. Two single doses of omaveloxolone 150 mg (taken in multiple 50 mg capsules) will be administered to the subjects beginning in the fasted state (Period 1) with a crossover and then in the fed state (Period 2). Subjects will be confined beginning on Study Day -1 through the last PK blood draw on Study Day 6 during Period 1, and from Study Day 14 through the last PK blood draw on Study Day 20 during Period 2. |
| Effect (Fed) | EXPERIMENTAL | Subjects will be randomly assigned to one of the two treatment sequences. Two single doses of omaveloxolone 150 mg (taken in multiple 50 mg capsules) will be administered to the subjects beginning in the fed state (Period 1) with a crossover and then in the fasted state (Period 2). Subjects will be confined beginning on Study Day -1 through the last PK blood draw on Study Day 6 during Period 1, and from Study Day 14 through the last PK blood draw on Study Day 20 during Period 2. |
| Dose Proportionality | EXPERIMENTAL | Subjects will be randomly assigned to one of two omaveloxolone dosages. A single dose of omaveloxolone (in either 50 mg or 100 mg) will be administered to the subjects in 50 mg capsules in a fasted state. Subjects will be confined beginning on Study Day -1 through the last blood sample collection on Study Day 6. |
| Omaveloxolone 5 mg & ipilimumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, Dose1 taken orally once daily for 168 weeks, plus ipilimumab (3 mg/kg) administered at weeks 1, 4, 7, and 10. |
| Omaveloxolone 10 mg & ipilimumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 168 weeks, plus ipilimumab (3 mg/kg) administered at weeks 1, 4, 7, and 10. |
| Omaveloxolone 5 mg & nivolumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 5 mg taken orally once daily for 168 weeks, plus nivolumab (240 mg) administered every two weeks as clinically indicated. |
| Omaveloxolone 10 mg & nivolumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 10 mg taken orally once daily for 168 weeks, plus nivolumab (240 mg) administered every two weeks as clinically indicated. |
| Omaveloxolone 20 mg & nivolumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 20 mg taken orally once daily for 168 weeks, plus nivolumab (240 mg) administered every two weeks as clinically indicated. |
| Omaveloxolone 100 mg & nivolumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 100 mg taken orally once daily for 168 weeks, plus nivolumab (240 mg) administered every two weeks as clinically indicated. |
| Omaveloxolone 150 mg & nivolumab | EXPERIMENTAL | Omaveloxolone (RTA 408) capsules, 150 mg taken orally once daily for 168 weeks, plus nivolumab (240 mg) administered every two weeks as clinically indicated. |
| RTA 408 Capsules | EXPERIMENTAL | RTA 408 capsules, beginning dose 2.5 mg once daily, 28-day cycle, up to 12 cycles. Doses will increase by 100% of previous dose (e.g., 5 mg, 10 mg, 20 mg, etc.) until such time the Protocol Safety Review Committee decreases the escalation rate to 50% of the previous dose (e.g., 20 mg, 30 mg, 45 mg, etc). Dose escalation will continue until Maximum Tolerated Dose is identified. |
| Name | Type | Description |
|---|---|---|
| Omaveloxolone | DRUG | Administered as specified in the treatment arm. |
| Placebo | DRUG | Administered as specified in the treatment arm. |
| Omaveloxolone capsules, 2.5 mg | DRUG | - |
| omaveloxolone capsules, 5 mg | DRUG | - |
| omaveloxolone capsules, 10 mg | DRUG | - |
| Placebo capsules | DRUG | - |
| omaveloxolone capsules, 20 mg | DRUG | - |
| omaveloxolone capsules, 40 mg | DRUG | - |
| omaveloxolone capsules, 80 mg | DRUG | - |
| omaveloxolone capsules, 160 mg | DRUG | - |
| Omaveloxolone Capsules, 300 mg | DRUG | - |
| Omaveloxolone Capsules, 150 mg | DRUG | - |
| Omeprazole | DRUG | Oral tablet |
| Moxifloxacin | DRUG | Moxifloxacin capsules |
| Efavirenz | DRUG | Efavirenz Tablet, 600 mg, administered orally once daily |
| Omaveloxolone 50 mg capsules | DRUG | Capsules containing 50 mg of omaveloxolone |
| Midazolam oral solution | DRUG | 2 mg/mL oral solution |
| Repaglinide 1 MG | DRUG | 1 mg tablet |
| MetFORMIN 500 Mg Oral Tablet | DRUG | 500 mg tablet |
| Rosuvastatin | DRUG | 10 mg tablet |
| Digoxin tablet | DRUG | 0.25 mg tablet |
| Gemfibrozil Tablets | DRUG | 600 mg tablet |
| Itraconazole capsule | DRUG | 100 mg capsule |
| Verapamil Pill | DRUG | 120 mg tablet |
| [14C]-Omaveloxolone | DRUG | \[14C\]-Omaveloxolone 50 mg capsules |
| Omaveloxolone Capsules (2.5 mg/capsule) | DRUG | Capsules containing 2.5 mg of omaveloxolone per capsule to the dosage indicated in the Arm Label |
| Ipilimumab (3 mg/kg) | DRUG | Sterile solution containing ipilimumab to be delivered intravenously at 3mg/kg |
| Nivolumab (240 mg) | DRUG | Sterile solution containing nivolumab to be delivered intravenously at 240 mg |
| Omaveloxolone Capsules (10 mg/capsule) | DRUG | Capsules containing 10 mg of omaveloxolone per capsule to the dosage indicated in the Arm Label |
| Omaveloxolone Capsules (50 mg/capsule) | DRUG | Capsules containing 50 mg of omaveloxolone per capsule to the dosage indicated in the Arm Label |
Part 1: Key inclusion criteria: * Diagnosed with genetically confirmed Friedreich's Ataxia (FA), i.e., homozygous for guanine-adenine-adenine (GAA) repeat expansion in intron-1 of the frataxin gene, or GAA repeat expansion in 1 allele and with point mutations or deletions, or other non-GAA expansio...
Omaveloxolone is a small molecule being developed by Biogen Inc. (BIIB) for rare disease indications. It is currently in Phase 3 clinical development. The drug has been studied in multiple settings, including ocular inflammation and pain following surgery, melanoma, and healthy volunteer pharmacokinetic studies.
Omaveloxolone is being investigated for use in several conditions. Clinical trials have evaluated it for inflammation and pain following ocular surgery, in patients with unresectable or metastatic melanoma, and in healthy subjects for pharmacokinetic and cardiac safety studies. Its primary therapeutic area is rare disease.
Omaveloxolone is developed by Biogen Inc., a biotechnology company traded on NASDAQ under the ticker BIIB. Biogen is advancing the drug through clinical trials, with the most advanced studies in Phase 3.
Omaveloxolone is in Phase 3 clinical development. It has completed earlier phase trials, including Phase 1 and Phase 2 studies. The drug remains investigational and is not yet approved for any indication.
Omaveloxolone has been studied in several completed clinical trials. NCT02065375 was a Phase 2 study in ocular inflammation and pain following surgery. NCT02259231 was a Phase 1 trial in melanoma. NCT03664453 and NCT05927649 were Phase 1 studies in healthy volunteers.
Yes, omaveloxolone is also known as RTA 408. Clinical trial records refer to the drug as RTA 408 ophthalmic suspension in the ocular surgery study and as RTA 408 capsules in the melanoma trial. Both names refer to the same investigational compound.