Langsigtet opfølgningsundersøgelse for at evaluere sikkerhed og effektivitet af FBX-101 hos Krabbe-patienter
En langsigtet opfølgningsundersøgelse til evaluering af Krabbe-patienters sikkerhed og effekt fra kliniske forsøg med genterapi, der involverer administration af FBX-101 (AAVrh.10-hGALC)
This is an observational study that will enroll any patients with Krabbe disease that have participated in prior interventional clinical trials involving the administration of FBX-101.
Studieoversigt
Detaljeret beskrivelse
FBX-101-LTFU is a multicenter, non-interventional, Long-Term Follow-Up (LTFU) study of participants from prior interventional trials involving the administration of FBX-101. Eligible participants will undergo clinical evaluations at prespecified intervals for at least 3 years from the last visit in the prior clinical trial (up to 5 years post-FBX-101 treatment). Overall safety and additional signs of efficacy will be collected with a series of laboratory tests, diagnostic tests, and performance surveys. Additionally, children participating in interventional trials that are terminated early will be transferred to this LTFU study and will complete any pending visits from the interventional trial before starting the clinical evaluations included in this protocol.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
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North Carolina
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Durham, North Carolina, Forenede Stater, 27705
- Duke University
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
This is an observational long-term follow-up (LTFU) study of participants from prior interventional trials involving the administration of FBX-101.
Beskrivelse
Inclusion Criteria:
- Participants that have completed a prior clinical trial involving the administration of FBX-101.
- Parent(s)/legal guardian(s) of participant willing and able to complete the informed consent process and comply with study procedures and visit schedule.
Exclusion Criteria:
•Planned or current participation in any other interventional clinical study that may confound the safety or efficacy evaluation of FBX-101 during this study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: OTHER
- Tidsperspektiver: PROSPECTIVE
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
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Patients enrolled in the FBX-101-LTFU study
The participants will be followed for 36 months after they have concluded their participation in the interventional trial. They will complete 5 scheduled visits with assessments as specified in the schedule of assessments, to collect data for safety and additional signs of efficacy for FBX-101. Those patients enrolled from any other early terminated trial, will first complete pending evaluations from that trial. |
A replication-deficient adeno-associated virus gene transfer vector expressing the human galactocerebrosidase (hGALC) cDNA will be delivered one-time through a venous catheter inserted into a peripheral limb vein. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Langtidssikkerhed vurderet ud fra forekomsten af alvorlige bivirkninger (SAE'er) og bivirkninger af særlig interesse (AESI'er), der tilskrives FBX-101
Tidsramme: 36 måneder
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36 måneder
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Effekt som vurderet ved ændring af livskvalitet målt på langs af Pediatric Quality of Life (PedsQL) Generic Core Scales med Family Impact Module og Multidimensional Fatigue Scale
Tidsramme: 36 måneder
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36 måneder
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Effekt som vurderet ved ændring af udviklingsmæssige milepæle såsom sprog og motoriske færdigheder målt i længderetningen af et specifikt Developmental Milestones spørgeskema
Tidsramme: 36 måneder
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36 måneder
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Effektivitet vurderet ved ændring af visuel funktion målt i længderetningen ved visuelle fremkaldte potentialer (VEP)
Tidsramme: 36 måneder
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36 måneder
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Effekt som vurderet ved ændring af synsfunktion målt i længderetningen ved synsstyrke
Tidsramme: 36 måneder
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36 måneder
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Effekt som vurderet ved ændring af fuldblodsdonorkimerisme
Tidsramme: 36 måneder
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36 måneder
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Effekt som vurderet ved ændring af psykosin i fuldblod og plasma
Tidsramme: 36 måneder
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36 måneder
|
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Effekt som vurderet ved ændring af hørefunktion målt i længderetningen ved Behavior Audiometry (BAUD)
Tidsramme: 36 måneder
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36 måneder
|
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Effekt som vurderet ved ændring af perifer nerveledningshastighed målt i længderetningen ved vurdering af nerveledningshastighed (NCV)
Tidsramme: 36 måneder
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36 måneder
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Effektivitet vurderet ved ændring af fraktioneret anisotropi (FA) målt i længderetningen ved hjernemagnetisk resonansbilleddannelse (MRI) med diffusionstensorbilleddannelse (DTI)
Tidsramme: 36 måneder
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36 måneder
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Effekt som vurderet ved ændring af Galactosylceramidase (GALC) niveauer i plasma og cerebrospinalvæske (CSF)
Tidsramme: 36 måneder
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36 måneder
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Efficacy as assessed by change of gross motor function measured longitudinally by Peabody Developmental Motor Scale (PDMS-2)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
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Efficacy as assessed by change of gross motor function measured longitudinally by Bruininks-Oseretsky Test of Motor Proficiency (BOT-2)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
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Efficacy as assessed by change of gross motor function measured longitudinally by Gross Motor Function Measure 88 (GMFM-88)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
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Efficacy as assessed by change of fine motor function measured longitudinally by Mullen Scales of Early Learning (MSEL)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
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Efficacy as assessed by change of fine motor function measured longitudinally by Beery VMI Sixth Edition (VMI)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of fine motor function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of fine motor function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of cognitive function measured longitudinally by Mullen Scales of Early Learning (MSEL)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of cognitive function measured longitudinally by the Differential Ability Scale II (DAS-II)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of cognitive function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of adaptive behaviour function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3).
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of language function measured longitudinally by Mullen Scales of Early Learning (MSEL).
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of language function measured longitudinally by Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of language function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of language function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3).
Tidsramme: 36 months
|
The site is providing raw data and sponsor is calculating derived scores according to specific manual. Higher values will mean better outcome. |
36 months
|
|
Efficacy as assessed by change of hearing function measured longitudinally by Auditory Brainstem Responses (ABRs)
Tidsramme: 36 months
|
Absolute values for Waves I, III and V in milliseconds will be recorded along interpretation and waveform morphology; and also Auditory Brainstem Responses (corrected). |
36 months
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Generelle publikationer
- Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.
- Bascou N, DeRenzo A, Poe MD, Escolar ML. A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life. Orphanet J Rare Dis. 2018 Aug 9;13(1):126. doi: 10.1186/s13023-018-0872-9.
- Beltran-Quintero ML, Bascou NA, Poe MD, Wenger DA, Saavedra-Matiz CA, Nichols MJ, Escolar ML. Early progression of Krabbe disease in patients with symptom onset between 0 and 5 months. Orphanet J Rare Dis. 2019 Feb 18;14(1):46. doi: 10.1186/s13023-019-1018-4.
- Yoon IC, Bascou NA, Poe MD, Szabolcs P, Escolar ML. Long-term neurodevelopmental outcomes of hematopoietic stem cell transplantation for late-infantile Krabbe disease. Blood. 2021 Apr 1;137(13):1719-1730. doi: 10.1182/blood.2020005477.
- Wright MD, Poe MD, DeRenzo A, Haldal S, Escolar ML. Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study. Neurology. 2017 Sep 26;89(13):1365-1372. doi: 10.1212/WNL.0000000000004418. Epub 2017 Aug 30.
- Gupta A, Poe MD, Styner MA, Panigrahy A, Escolar ML. Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease. Neuroimage Clin. 2014 Sep 26;7:792-8. doi: 10.1016/j.nicl.2014.09.014. eCollection 2015.
- Bradbury AM, Bagel J, Swain G, Miyadera K, Pesayco JP, Assenmacher CA, Brisson B, Hendricks I, Wang XH, Herbst Z, Pyne N, Odonnell P, Shelton GD, Gelb M, Hackett N, Szabolcs P, Vite CH, Escolar M. Combination HSCT and intravenous AAV-mediated gene therapy in a canine model proves pivotal for translation of Krabbe disease therapy. Mol Ther. 2024 Jan 3;32(1):44-58. doi: 10.1016/j.ymthe.2023.11.014. Epub 2023 Nov 11.
- Siddiqi ZA, Sanders DB, Massey JM. Peripheral neuropathy in Krabbe disease: effect of hematopoietic stem cell transplantation. Neurology. 2006 Jul 25;67(2):268-72. doi: 10.1212/01.wnl.0000230156.01228.33.
- Vander Lugt MT, Chen X, Escolar ML, Carella BA, Barnum JL, Windreich RM, Hill MJ, Poe M, Marsh RA, Stanczak H, Stenger EO, Szabolcs P. Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders. Blood Adv. 2020 Jul 14;4(13):3041-3052. doi: 10.1182/bloodadvances.2020001940.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
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
- Demyeliniserende sygdomme
- Lipidmetabolismeforstyrrelser
- Hjernesygdomme, metaboliske, medfødte
- Hjernesygdomme, metaboliske
- Arvelige demyeliniserende sygdomme i centralnervesystemet
- Leukoencefalopati
- Lipidmetabolisme, medfødte fejl
- Lysosomale opbevaringssygdomme, nervesystemet
- Sphingolipidoser
- Lipidoser
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Ernæringsmæssige og metaboliske sygdomme
- Lysosomale opbevaringssygdomme
- Leukodystrofi, globoidcelle
Andre undersøgelses-id-numre
- PRO00120964
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