Undersøgelse af UX701 genoverførsel til behandling af Wilsons sygdom
En randomiseret, dobbeltblind, placebokontrolleret, multicenter, sømløs, adaptiv, sikkerhed, dosisfinding og fase 3 klinisk undersøgelse af UX701 AAV-medieret genoverførsel til behandling af Wilsons sygdom
The primary objectives of this study are to evaluate the safety of single IV doses of UX701 in patients with Wilson disease, to select the UX701 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the effect of UX701 on copper regulation.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Stage 1 (Phase 1/2) is an open-label safety and dose-finding stage designed to evaluate the safety and efficacy of 4 dose levels of UX701 to establish initial safety of UX701 and select a safe and efficacious dose for further evaluation. Stage 2 (Phase 3) is a randomized, open-label, active-controlled stage to evaluate the safety and efficacy of UX701 using the dose selected in Stage 1. Stage 3 is a long-term follow-up stage designed to evaluate the safety, efficacy, and clinical benefit of UX701 for at least 5 years from the time of UX701 administration.
Participants who receive UX701 will receive premedication, prophylactic oral corticosteroids and immunomodulation therapy.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
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Surrey
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London, Surrey, Det Forenede Kongerige, SE5 9RS
- Kings College NHS Foundation
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California
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Los Angeles, California, Forenede Stater, 90095
- University of California Los Angeles
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Redwood City, California, Forenede Stater, 94063
- Stanford University
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Sacramento, California, Forenede Stater, 95817-1348
- University of California Davis
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Indiana University
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Duke University Medical Center
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Ohio
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Cleveland, Ohio, Forenede Stater, 44106
- University Hospitals Cleveland Medical Center
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37212-2700
- Vanderbilt University Medical Center
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Utah
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Salt Lake City, Utah, Forenede Stater, 84132
- University of Utah
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Washington
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Seattle, Washington, Forenede Stater, 98105
- Seattle Children's Hospital
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Lisbon District
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Lisbon, Lisbon District, Portugal, 1649-035
- Centro Hospitalar Universitário Lisboa Norte
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Porto District
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Porto, Porto District, Portugal, 4200-319
- Centro Hospitalar Universitário de São João
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Barcelona, Spanien, 08035
- Hospital Universitario Vall d'Hebron - PPDS
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Key Inclusion Criteria:
- Confirmed diagnosis of Wilson disease based on genetic confirmation of heterozygous or homozygous biallelic ATP7B mutation.
- Stable Wilson disease as evidenced by ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 2 months at screening, with no medication or dose changes for at least 2 months at screening.
- Ongoing restriction of high copper containing foods for at least 2 months at Screening and continued through study participation.
- Willing and able to comply with all study procedures and requirements, including frequent blood collection, total urine collection over a 24-hour period, patient-reported outcome assessments, and long-term follow-up
Key Exclusion Criteria:
- Detectable pre-existing antibodies to the AAV9 capsid.
- Stage 1 only: History of copper chelator or zinc therapy noncompliance, in the Investigator's judgment, within 6 months prior to Screening.
- History of liver transplant.
- Active decompensated hepatic cirrhosis or history of hepatic encephalopathy.
- Significant hepatic inflammation as evidenced by laboratory abnormalities.
- Model for End-Stage Liver Disease (MELD) score > 13.
- Hemoglobin < 9 g/dL
- Presence of Stage 3 or higher chronic kidney disease based on estimated glomerular filtration rate < 60 mL/min/1.73 m2.
- Marked neurological deficit or compromise that, in the Investigator's opinion, would interfere with the subject's safety or ability to participate in the study.
- Moderate to severe depression, recent or active suicidal ideation with intent or suicidal behavior, psychosis, or unstable psychiatric illness.
- Known hypersensitivity to UX701 or its excipients, copper chelators, zinc, rituximab, tacrolimus, corticosteroids, or eculizumab that, in the Investigator's judgement, places the participant at increased risk for adverse events.
- Participation in another gene transfer study or use of another gene transfer product before or during study participation.
- Subjects with known hypersensitivity to amide-containing local anesthetics are excluded from participating in the optional liver biopsy substudy.
Note: Other protocol defined Inclusion/ Exclusion criteria may apply
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Enkelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Stage 1: UX701 Dose Level 1
Participants receive a single, peripheral intravenous (IV) infusion of UX701 at dose level 1. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
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Eksperimentel: Stage 1: UX701 Dose Level 2
Participants receive a single, peripheral IV infusion of UX701 at dose level 2. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
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Eksperimentel: Stage 1: UX701 Dose Level 3
Participants receive a single, peripheral IV infusion of UX701 at dose level 3. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
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Eksperimentel: Stage 1: UX701 Dose Level 4
Participants receive a single, peripheral IV infusion of UX701 at dose level 4. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
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Eksperimentel: Stage 2: UX701 at Selected Dose
Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at the selected dose. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
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Eksperimentel: Stage 2: Standard of Care (SOC) to UX701
Participants randomized to SOC will continue their baseline SOC medications for 52 weeks, followed by a single, peripheral IV infusion of UX701 at the selected dose. Following UX701 administration, participants will be evaluated for modification of their SOC medications. |
Nonreplicating, recombinant gene transfer vector
Andre navne:
SOC treatment (i.e., copper chelators and/or zinc) administered according to standard regimens. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
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Trin 1: Forekomst af behandlings-emergent adverse events (TEAE'er), Treatment-Emergent Serious Adverse Events (TESAE'er), Adverse Events of Special Interest (AESI'er), behandlingsrelaterede TEAE'er og behandlingsrelaterede TESAE'er
Tidsramme: Op til uge 52
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Op til uge 52
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Trin 1: Ændring i 24-timers urinkobberkoncentration fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Ændring i total kobber fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Ændring i ceruloplasmin fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Ændring i ikke-ceruloplasmin-bundet kobber (NCC) fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Ændring i gratis kobber fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Ændring i ceruloplasminaktivitet fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 1: Procentvis reduktion i standardbehandlingsmedicin (SOC) inden uge 52
Tidsramme: Uge 52
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Uge 52
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Trin 1: Antal deltagere, der stopper med SOC-medicin efter uge 52
Tidsramme: Uge 52
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Uge 52
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Trin 1: Antal sammenhængende uger med SOC-medicinering i uge 52
Tidsramme: Uge 52
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Uge 52
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Trin 2: Ændring i 24-timers urinkobberkoncentration fra baseline i uge 52, vurderet for overlegenhed
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 2: Procent reduktion i SOC-medicin efter uge 52, vurderet for overlegenhed
Tidsramme: Uge 52
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Uge 52
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Trin 1: Ændring i ceruloplasmin-bundet kobber fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Sekundære resultatmål
Resultatmål |
Tidsramme |
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Trin 2: Ændring i Ceruloplasmin-aktivitetsniveauer fra baseline i uge 52, evalueret for overlegenhed
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Trin 2: Antal deltagere, der ophører med SOC-medicin i uge 52
Tidsramme: Uge 52
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Uge 52
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Trin 2: Ændring i leverkobberkoncentration vurderet ved leverbiopsi fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Fase 2: Ændring i FACIT-træthedsskalaresultat fra baseline i uge 52
Tidsramme: Baseline, uge 52
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Baseline, uge 52
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Andre resultatmål
Resultatmål |
Tidsramme |
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Trin 2: Udvikling af anti-ATP7B antistoffer
Tidsramme: Op til uge 104
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Op til uge 104
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Trin 2: Forekomst af TEAE'er, TESAE'er, AESI'er, behandlingsrelaterede TEAE'er og behandlingsrelaterede TESAE'er
Tidsramme: Op til uge 312
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Op til uge 312
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Medical Director, Ultragenyx Pharmaceutical Inc
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Metabolisme, medfødte fejl
- Genetiske sygdomme, medfødte
- Metaboliske sygdomme
- Sygdomme i fordøjelsessystemet
- Neurodegenerative sygdomme
- Leversygdomme
- Bevægelsesforstyrrelser
- Heredodegenerative lidelser, nervesystem
- Basal Ganglia Sygdomme
- Hjernesygdomme, metaboliske, medfødte
- Hjernesygdomme, metaboliske
- Metalmetabolisme, medfødte fejl
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Ernæringsmæssige og metaboliske sygdomme
- Hepatolentikulær degeneration
- Sundhedstjenester Administration
- Sundhedsvæsenets kvalitet, adgang og evaluering
- Sundhedskvalitet
- Kvalitetsindikatorer, sundhedsvæsenet
- Standard for pleje
Andre undersøgelses-id-numre
- UX701-CL301
- 2020-005266-34 (EudraCT nummer)
- 2022-502873-40-00 (Anden identifikator: EU CT Number)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Due to the rarity of Wilson Disease, individual patient data will not be shared in order to safeguard patient privacy. The study protocol and statistical analysis plan for this study will be available with the tabulated results once posted.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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