Langzeit-Follow-up-Studie zur Bewertung der Sicherheit und Wirksamkeit von FBX-101 bei Krabbe-Patienten
Eine Langzeit-Follow-up-Studie zur Bewertung der Sicherheit und Wirksamkeit von Krabbe-Patienten aus klinischen Gentherapiestudien, die die Verabreichung von FBX-101 (AAVrh.10-hGALC) beinhalteten.
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.
Studienübersicht
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
-
-
North Carolina
-
Durham, North Carolina, Vereinigte Staaten, 27705
- Duke University
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Kind
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
This is an observational long-term follow-up (LTFU) study of participants from prior interventional trials involving the administration of FBX-101.
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: OTHER
- Zeitperspektiven: PROSPECTIVE
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
|
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. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Langfristige Sicherheit, bewertet anhand der Häufigkeit schwerwiegender unerwünschter Ereignisse (SAEs) und unerwünschter Ereignisse von besonderem Interesse (AESIs), die auf FBX-101 zurückzuführen sind
Zeitfenster: 36 Monate
|
36 Monate
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Die Wirksamkeit wird anhand der Veränderung der Lebensqualität bewertet, die in Längsrichtung anhand der generischen Kernskalen der pädiatrischen Lebensqualität (PedsQL) mit Family Impact Module und der multidimensionalen Müdigkeitsskala gemessen wird
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Veränderung von Entwicklungsmeilensteinen wie Sprache und motorischen Fähigkeiten bewertet, die im Längsschnitt anhand eines spezifischen Fragebogens zu Entwicklungsmeilensteinen gemessen werden
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Veränderung der Sehfunktion beurteilt, die in Längsrichtung anhand der visuell evozierten Potenziale (VEP) gemessen wird.
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Veränderung der Sehfunktion beurteilt, die in Längsrichtung anhand der Sehschärfe gemessen wird
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Wirksamkeit anhand der Veränderung des Chimärismus des Vollblutspenders
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Wirksamkeit anhand der Veränderung des Psychosins in Vollblut und Plasma
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Änderung der Hörfunktion beurteilt, die in Längsrichtung mittels Verhaltensaudiometrie (BAUD) gemessen wird.
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Änderung der peripheren Nervenleitungsgeschwindigkeit beurteilt, die in Längsrichtung durch Bewertungen der Nervenleitungsgeschwindigkeit (Nerven Conduction Velocity, NCV) gemessen wird
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Die Wirksamkeit wird anhand der Änderung der fraktionalen Anisotropie (FA) bewertet, die in Längsrichtung mittels Magnetresonanztomographie (MRT) des Gehirns mit Diffusionstensor-Bildgebung (DTI) gemessen wird.
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Wirksamkeit anhand der Veränderung der Galactosylceramidase (GALC)-Spiegel im Plasma und in der Zerebrospinalflüssigkeit (CSF)
Zeitfenster: 36 Monate
|
36 Monate
|
|
|
Efficacy as assessed by change of gross motor function measured longitudinally by Peabody Developmental Motor Scale (PDMS-2)
Zeitfenster: 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 gross motor function measured longitudinally by Bruininks-Oseretsky Test of Motor Proficiency (BOT-2)
Zeitfenster: 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 gross motor function measured longitudinally by Gross Motor Function Measure 88 (GMFM-88)
Zeitfenster: 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 Mullen Scales of Early Learning (MSEL)
Zeitfenster: 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 Beery VMI Sixth Edition (VMI)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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).
Zeitfenster: 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).
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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).
Zeitfenster: 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)
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Gehirns
- Erkrankungen des zentralen Nervensystems
- Erkrankungen des Nervensystems
- Stoffwechsel, angeborene Fehler
- Genetische Krankheiten, angeboren
- Stoffwechselerkrankungen
- Demyelinisierende Krankheiten
- Störungen des Fettstoffwechsels
- Gehirnerkrankungen, Stoffwechselerkrankungen, angeboren
- Gehirnerkrankungen, Stoffwechsel
- Erbliche Demyelinisierungskrankheiten des Zentralnervensystems
- Leukenzephalopathien
- Fettstoffwechsel, angeborene Fehler
- Lysosomale Speicherkrankheiten, Nervensystem
- Sphingolipidosen
- Lipidosen
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Ernährungs- und Stoffwechselerkrankungen
- Lysosomale Speicherkrankheiten
- Leukodystrophie, Globoidzelle
Andere Studien-ID-Nummern
- PRO00120964
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .