Long-term Follow-up Study to Evaluate Safety and Efficacy of FBX-101 in Krabbe Patients

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Krabbe Disease
• Intervention / Treatment: Biological: 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.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Kelly Bossola; Phone Number: +1.380.239.2052; Email: advocacy@forgebiologics.com
• Study Contact Backup: Name: Maria Escolar; Phone Number: +1.412-499-4658; Email: advocacy@forgebiologics.com

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospitals - Michigan Medicine
      • Contact: Mark Vander Lugt, MD; Phone Number: 616-340-7643; Email: marvande@med.umich.edu
      • Contact: Elise Kwasniewski; Phone Number: 734-615-6585; Email: ekwasnie@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Biological: FBX-101; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		36 months
Efficacy as assessed by change of developmental milestones such as language and motor skills as measured longitudinally by an specific Developmental Milestones questionnaire		36 months
Efficacy as assessed by change of visual function as measured longitudinally by visual evoked potentials (VEP)		36 months
Efficacy as assessed by change of visual function as measured longitudinally by visual acuity		36 months
Efficacy as assessed by change of whole blood donor chimerism		36 months
Efficacy as assessed by change of psychosine in whole blood and plasma		36 months
Efficacy as assessed by change of gross motor function measured longitudinally by Peabody Developmental Motor Scale (PDMS-2)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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).	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).	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)	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)	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).	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)	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
Efficacy as assessed by change of hearing function measured longitudinally by Behavior Audiometry (BAUD)		36 months
Efficacy as assessed by change of peripheral nerve conduction velocity measured longitudinally by Nerve Conduction Velocity (NCV) assessments		36 months
Efficacy as assessed by change of Fractional Anisotropy (FA) as measured longitudinally by brain Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI)		36 months
Efficacy as assessed by change of Galactosylceramidase (GALC) levels in plasma and Cerebrospinal Fluid (CSF)		36 months

Collaborators and Investigators

• Sponsor: Forge Biologics, Inc

Publications and helpful links

General Publications

• 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. Erratum In: Blood Adv. 2020 Aug 11;4(15):3508.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Estimated): May 15, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Leukodystrophy; Lysosomal Storage Disorder; Globoid Cell Leukodystrophy; GALC
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Leukoencephalopathies; Hereditary Central Nervous System Demyelinating Diseases; Leukodystrophy, Globoid Cell
• Other Study ID Numbers: FBX-101-LTFU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No