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RTA 408 kapsler til patienter med Friedreichs ataksi - MOXIe

13. august 2026 opdateret af: Biogen

En fase 2-undersøgelse af sikkerheden, effektiviteten og farmakodynamikken af ​​RTA 408 i behandlingen af ​​Friedreichs ataksi (MOXIe)

Friedreichs ataksi er en autosomal recessiv cerebellar ataksi forårsaget af triplet-gentagne udvidelser. Den forårsagende mutation er en gentagen trinukleotid (GAA) ekspansion i den første intron af frataxingenet, hvilket fører til svækket transkription af frataxin. De patologiske konsekvenser af frataxin-mangel inkluderer en alvorlig forstyrrelse af jern-svovl-klyngebiosyntesen, mitokondriel jernoverbelastning koblet til cellulær jerndysregulering og en øget følsomhed over for oxidativt stress.

Et kendetegn ved Friedreichs ataksi er svækkelse af antioxidative forsvarsmekanismer, som spiller en stor rolle i sygdomsprogression. Undersøgelser har vist, at nuklear faktor erythroid-afledt 2-relateret faktor 2 (Nrf2) signalering er kraftigt svækket hos patienter med Friedreichs ataksi. Derfor antages omaveloxolons (RTA 408) evne til at aktivere Nrf2 og inducere antioxidantmålgener at være terapeutisk hos patienter med Friedreichs ataksi.

Denne 2-delte undersøgelse vil evaluere effektiviteten, sikkerheden og farmakodynamikken af ​​omaveloxolone (RTA 408) i behandlingen af ​​patienter med Friedreichs ataksi.

Del 1: Den første del af denne undersøgelse vil være et randomiseret, placebokontrolleret, dobbeltblindt, dosis-eskaleringsstudie for at evaluere sikkerheden af ​​omaveloxolon (RTA 408) ved forskellige doser hos patienter med Friedreichs ataksi.

Del 2: Anden del af denne undersøgelse er et randomiseret, placebo-kontrolleret, dobbelt-blindt, parallel-gruppe studie for at evaluere sikkerheden og effekten af ​​omaveloxolone (RTA 408) 150 mg hos patienter med Friedreichs ataksi. Patienter indskrevet i del 2 vil blive randomiseret 1:1 til at modtage omaveloxolone (RTA 408) 150 mg eller placebo.

Forlængelse: Udvidelsen vil vurdere langsigtet sikkerhed og tolerabilitet af omaveloxolone (RTA 408) hos kvalificerede patienter med Friedreichs ataksi efter afslutning af del 1 eller del 2. Patienter vil ikke blive afblindet for at studere behandling i del 1 eller del 2, når de går ind i forlængelsesstudie. Patienterne vil modtage åbent omaveloxolon (RTA 408) på 150 mg én gang dagligt.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Denne undersøgelse er tidligere udgivet af Reata Pharmaceuticals. I september 2023 blev sponsoratet af forsøget overført til Biogen.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

172

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
    • Victoria
      • Parkville, Victoria, Australien, 3052
        • Murdoch Childrens Research Institute
  • Det Forenede Kongerige
      • London, Det Forenede Kongerige, WC1E 6BT
        • University College of London
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90095
        • UCLA
    • Florida
      • Gainesville, Florida, Forenede Stater, 32610
        • University of Florida - Neurology
      • Tampa, Florida, Forenede Stater, 33612
        • USF Ataxia Research Center
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30329
        • Emory University Hospital - Neurology
    • Iowa
      • Iowa City, Iowa, Forenede Stater, 52242
        • University of Iowa Stead Family Children's Hospital
    • Ohio
      • Columbus, Ohio, Forenede Stater, 43221
        • Ohio State University - Neurology
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Children's Hospital of Philadelphia
  • Italien
      • Milan, Italien, 20133
        • Neurological Institute Carlo Besta
  • Østrig
      • Innsbruck, Østrig, 6020
        • Medical University Innsbruck

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

16 år til 40 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  1. Har genetisk bekræftet Friedreichs ataksi
  2. Har en ændret FARS-score ≥20 og ≤80
  3. Være mand eller kvinde og ≥16 år og ≤40 år
  4. Har ingen ændringer i træningsregimet inden for 30 dage før studiedag 1 og vær villig til at forblive på det samme træningsregime i løbet af den 16-ugers studieperiode
  5. Har evnen til at gennemføre maksimal træningstest
  6. Kunne sluge kapsler

Ekskluderingskriterier:

  1. Har ukontrolleret diabetes (HbA1c >11,0%)
  2. Har B-type natriuretisk peptidværdi >200 pg/ml
  3. Har en historie med klinisk signifikant venstresidig hjertesygdom og/eller klinisk signifikant hjertesygdom
  4. Har kendt aktiv svampe-, bakterie- og/eller virusinfektion, herunder human immundefektvirus eller hepatitisvirus (B eller C)
  5. Har kendt eller mistænkt aktivt stof- eller alkoholmisbrug
  6. Har klinisk signifikante abnormiteter i klinisk hæmatologi eller biokemi, herunder, men ikke begrænset til, forhøjelser større end 1,5 gange den øvre grænse for normalen for aspartataminotransferase eller alaninaminotransferase
  7. Har en unormal laboratorietestværdi eller alvorlig allerede eksisterende medicinsk tilstand, som efter investigatorens mening ville bringe patienten i fare ved tilmelding til studiet

  8. Har taget nogen af ​​følgende lægemidler inden for 7 dage før undersøgelsesdag 1 eller planlægger at tage nogen af ​​disse lægemidler i løbet af studiets deltagelse:

    1. Følsomme substrater for cytochrom P450 2C8 eller 3A4 (f.eks. repaglinid, midazolam, sildenafil)
    2. Moderate eller stærke hæmmere eller inducere af cytochrom P450 3A4 (f.eks. carbamazepin, phenytoin, ciprofloxacin, grapefrugtjuice)
    3. Substrater til p-glykoproteintransporter (f.eks. ambrisentan, digoxin)
  9. Har deltaget i andre interventionelle kliniske undersøgelser inden for 30 dage før undersøgelsesdag 1
  10. Har en kognitiv svækkelse, der kan udelukke evnen til at overholde undersøgelsesprocedurer
  11. Forudgående deltagelse i et forsøg med omaveloxolone (RTA 408)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Part 1: Omaveloxolone 2.5 and 5 mg
Participants received omaveloxolone 2.5 mg, oral capsule, QD for 2 weeks, followed by 5 mg Omaveloxolone, oral capsule, QD for 10 weeks.
Medicin: Omaveloxolone kapsler, 2,5 mg
Andre navne:
  • RTA 408 Kapsler 2,5 mg
Medicin: Omaveloxolone kapsler, 5 mg
Andre navne:
  • RTA 408 kapsler, 5 mg
Eksperimentel: Part 1: Omaveloxolone 10 mg
Participants received omaveloxolone 10 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 10 mg
Andre navne:
  • RTA 408 kapsler, 10 mg
Eksperimentel: Part 1: Omaveloxolone 20 mg
Participants received omaveloxolone 20 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 20 mg
Andre navne:
  • RTA 408 kapsler, 20 mg
Eksperimentel: Part 1: Omaveloxolone 40 mg
Participants received omaveloxolone 40 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 40 mg
Andre navne:
  • RTA 408 kapsler, 40 mg
Eksperimentel: Part 1: Omaveloxolone 80 mg
Participants received omaveloxolone 80 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 80 mg
Andre navne:
  • RTA 408 kapsler, 80 mg
Eksperimentel: Part 1: Omaveloxolone 160 mg
Participants received omaveloxolone 160 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 160 mg
Andre navne:
  • RTA 408 kapsler, 160 mg
Eksperimentel: Part 1: Omaveloxolone 300 mg
Participants received omaveloxolone 300 mg, oral capsule, QD for 12 weeks.
Medicin: Omaveloxolone kapsler, 300 mg
Andre navne:
  • RTA 408 kapsler, 300 mg
Placebo komparator: Part 1: Placebo
Participants received placebo, oral capsule, QD for 12 weeks.
Medicin: Placebo
Eksperimentel: Part 2: Omaveloxolone 150 mg
Participants received omaveloxolone 150 mg, oral capsule, QD for 48 weeks.
Medicin: Omaveloxolone kapsler, 150 mg
Andre navne:
  • RTA 408 kapsler, 150 mg
Placebo komparator: Part 2: Placebo
Participants received placebo, oral capsule, QD for 48 weeks.
Medicin: Placebo
Eksperimentel: OLE: Placebo/ Omaveloxolone
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).
Medicin: Omaveloxolone kapsler, 150 mg
Andre navne:
  • RTA 408 kapsler, 150 mg
Eksperimentel: OLE: Omaveloxolone/ Omaveloxolone
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).
Medicin: Omaveloxolone kapsler, 150 mg
Andre navne:
  • RTA 408 kapsler, 150 mg

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Part 1: Change From Baseline in Peak Work During Maximal Exercise Testing at Week 12
Tidsramme: Baseline, Week 12
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.
Baseline, Week 12
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Tidsramme: From first dose of study drug up to end of Part 1 of the study (up to Week 16)
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.
From first dose of study drug up to end of Part 1 of the study (up to Week 16)
Part 2: Change From Baseline in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48
Tidsramme: Baseline, Week 48
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.
Baseline, Week 48
Part 2: Number of Participants With TEAEs and TESAEs
Tidsramme: From first dose of study drug up to end of Part 2 of the study (up to Week 52)
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.
From first dose of study drug up to end of Part 2 of the study (up to Week 52)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Part 1: Change From Baseline in the mFARS at Week 12
Tidsramme: Baseline, Week 12
The 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.
Baseline, Week 12
Part 2: Number of Participants With Patient Global Impression of Change (PGI-C)
Tidsramme: Week 48
The PGI-C is a 7-point scale that requires participants to assess how much their illness has improved or worsened relative to their baseline state at the beginning of the trial. Participants self-rated their perceived change by completing the following statement: "Since I began trial treatment, my overall status is:" 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse and 7=Very much worse. Lower score indicates better improvement. The categories with at least one participant having a PGI-C score are reported.
Week 48
Part 2: Number of Participants With Clinical Global Impression of Change (CGI-C)
Tidsramme: Week 48
The CGIC scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of an intervention. The CGIC was assessed by completing the following statement "Compared to the participant's condition at the start of the trial, this participant's overall status is", where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. Lower score indicates better improvement. The categories with at least one participant having a CGIC score are reported.
Week 48
Part 2: Change From Baseline in Performance on a 9-Hole Peg Test (9-HPT) at Week 48
Tidsramme: Baseline, Week 48
The 9-HPT is a brief, standardized, quantitative test of upper extremity (arm and hand) function. Both the dominant and nondominant hands were tested twice (2 consecutive trials of the dominant hand, followed immediately by 2 consecutive trials of the nondominant hand). The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. The times recorded for the two trials for each hand are averaged, and the reciprocal average value for each hand was used in analyses. Longer test times reflect more impairment on the participant's upper extremity function, thus a negative change from baseline suggests an improvement.
Baseline, Week 48
Part 2: Change From Baseline in Performance on a 25-Foot Timed Walk Test (T25-FWT) at Week 48
Tidsramme: Baseline, Week 48
The T25-FWT is a quantitative mobility and leg function performance test based on time (in seconds) to complete a 25-foot walk. Participants were instructed to attempt two T25-FWT trials at each visit. Both walk times were averaged, and the reciprocal average value was used in analyses. Longer test times reflect more impairment on the participant's ability to walk, thus a negative change from baseline suggests an improvement.
Baseline, Week 48
Part 2: Total Number of Falls
Tidsramme: Up to Week 48
A fall was defined as "the participant unintentionally coming to rest on the ground or at a lower level." The total number of falls before and after study drug administration has been reported.
Up to Week 48
Part 2: Change From Baseline in Peak Work During Maximal Exercise Testing at Week 48
Tidsramme: Baseline, Week 48
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.
Baseline, Week 48
Part 2: Change From Baseline in the Activities of Daily Living (ADL) Score at Week 48
Tidsramme: Baseline, Week 48
The ADL scale examines the ability of participants to complete everyday tasks (e.g., holding a fork, dressing). The ADL is a 9-question assessment, with the total score being the sum of 9 questions. The ADL survey assesses 9 concepts: (1) speech; (2) swallowing; (3) cutting food and handling utensils; (4) dressing; (5) personal hygiene; (6) falling; (7) walking; (8) quality of sitting position; and (9) bladder function. Each of these is rated on a 5-point scale where 0= normal and 4= severe disability/inability to carry out activity independently, for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. A negative change from baseline indicates improvement.
Baseline, Week 48

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Biogen

Samarbejdspartnere

AbbVie
Friedreich's Ataxia Research Alliance

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

31. januar 2015

Primær færdiggørelse (Faktiske)

31. oktober 2019

Studieafslutning (Faktiske)

19. december 2025

Datoer for studieregistrering

Først indsendt

30. september 2014

Først indsendt, der opfyldte QC-kriterier

30. september 2014

Først opslået (Anslået)

2. oktober 2014

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

13. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • RTA 408-C-1402
  • 2024-517436-22 (Anden identifikator: EU CTIS Number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

I overensstemmelse med Biogens politik for gennemsigtighed og datadeling i kliniske forsøg på https://www.biogentrialtransparency.com/

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Ingen

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Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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