Clinical trial NCT06308718: Long-term Follow-up Study to Evaluate Safety and Efficacy of FBX-101 in Krabbe Patients
Official title: A Long-term Follow-up Study to Evaluate Safety and Efficacy of Krabbe Patients From Gene Therapy Clinical Trials Involving the Administration of FBX-101 (AAVrh.10-hGALC)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Krabbe Disease
Keywords: Lysosomal Storage Disorder
Globoid Cell Leukodystrophy
Leukodystrophy
GALC
Lead sponsor: Forge Biologics, Inc
Sponsor class: INDUSTRY
First posted: 2024-03-13
Enrollment: 25
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is an observational long-term follow-up (LTFU) study of participants from prior interventional trials involving the administration of FBX-101.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Long Term safety as assessed by incidence of Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) that are attributed to FBX-101
timeFrame: 36 months
Secondary outcomes:
measure: Efficacy as assessed by change of gross motor function measured longitudinally by Peabody Developmental Motor Scale (PDMS-2)
timeFrame: 36 months
measure: Efficacy as assessed by change of gross motor function measured longitudinally by Bruininks-Oseretsky Test of Motor Proficiency (BOT-2)
timeFrame: 36 months
measure: Efficacy as assessed by change of gross motor function measured longitudinally by Gross Motor Function Measure 88 (GMFM-88)
timeFrame: 36 months
measure: Efficacy as assessed by change of fine motor function measured longitudinally by Mullen Scales of Early Learning (MSEL)
timeFrame: 36 months
measure: Efficacy as assessed by change of fine motor function measured longitudinally by Beery VMI Sixth Edition (VMI)
timeFrame: 36 months
measure: Efficacy as assessed by change of fine motor function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
timeFrame: 36 months
measure: Efficacy as assessed by change of fine motor function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3)
timeFrame: 36 months
measure: Efficacy as assessed by change of cognitive function measured longitudinally by Mullen Scales of Early Learning (MSEL)
timeFrame: 36 months
measure: Efficacy as assessed by change of cognitive function measured longitudinally by the Differential Ability Scale II (DAS-II)
timeFrame: 36 months
measure: Efficacy as assessed by change of cognitive function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
timeFrame: 36 months
measure: Efficacy as assessed by change of adaptive behaviour function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3).
timeFrame: 36 months
measure: Efficacy as assessed by change of language function measured longitudinally by Mullen Scales of Early Learning (MSEL).
timeFrame: 36 months
measure: Efficacy as assessed by change of language function measured longitudinally by Clinical Evaluation of Language Fundamentals Fifth Edition (CELF-5)
timeFrame: 36 months
measure: Efficacy as assessed by change of language function measured longitudinally by Bayley Scales of Infant Development (Bayley-III)
timeFrame: 36 months
measure: Efficacy as assessed by change of language function measured longitudinally by Vineland Adaptive Behavior Scale (Vineland 3).
timeFrame: 36 months
measure: Efficacy as assessed by change of quality of life measured longitudinally by the Pediatric Quality of Life (PedsQL) Generic Core Scales with Family Impact Module and Multidimensional Fatigue Scale
timeFrame: 36 months
measure: Efficacy as assessed by change of developmental milestones such as language and motor skills as measured longitudinally by an specific Developmental Milestones questionnaire
timeFrame: 36 months
measure: Efficacy as assessed by change of hearing function measured longitudinally by Auditory Brainstem Responses (ABRs)
timeFrame: 36 months
measure: Efficacy as assessed by change of hearing function measured longitudinally by Behavior Audiometry (BAUD)
timeFrame: 36 months
measure: Efficacy as assessed by change of peripheral nerve conduction velocity measured longitudinally by Nerve Conduction Velocity (NCV) assessments
timeFrame: 36 months
measure: Efficacy as assessed by change of Fractional Anisotropy (FA) as measured longitudinally by brain Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI)
timeFrame: 36 months
measure: Efficacy as assessed by change of visual function as measured longitudinally by visual evoked potentials (VEP)
timeFrame: 36 months
measure: Efficacy as assessed by change of visual function as measured longitudinally by visual acuity
timeFrame: 36 months
measure: Efficacy as assessed by change of whole blood donor chimerism
timeFrame: 36 months
measure: Efficacy as assessed by change of psychosine in whole blood and plasma
timeFrame: 36 months
measure: Efficacy as assessed by change of Galactosylceramidase (GALC) levels in plasma and Cerebrospinal Fluid (CSF)
timeFrame: 36 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals - Michigan Medicine
state: Michigan
Study officials:
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.