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Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously With HSCT
Bu çalışma, FBX-101 adlı bir gen tedavisini, daha önce kök hücre nakli (HSCT) yapılmış ya da yapılacak olan infantil ve geç infantil Krabbe hastalığı (Krabbe disease) olan çocuklarda inceliyor. Çalışmaya, GALC enzim düzeyi ve genetik/klinik bulgularla tanısı doğrulanmış, kök hücre nakli adayı ya da nakil olmuş bebekler alınmaktadır. Çalışma Faz 1/Faz 2 aşamasında yürütülmekte; şu an katılımcı almamakta ancak devam etmektedir (active, not recruiting).
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: 1. Group Infantile Krabbe: Subjects who are going to be transplanted or have already been transplanted for asymptomatic infantile onset Krabbe disease with initial diagnosis based on: 1. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of infantile Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: 2. Psychosine levels predictive of infantile onset by Dried Blood Spot (DBS); OR 3. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR 4. Two GALC mutations predictive to result in infantile onset phenotype. 2. Group Late Infantile Krabbe: Subjects who are going to be transplanted or have already been transplanted for symptomatic late infantile onset Krabbe with initial diagnosis based on: 1. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of late infantile Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: 2. Psychosine levels predictive of late infantile onset by DBS; OR 3. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR 4. Two GALC mutations predictive to result in late infantile onset phenotype; OR 5. Neurological/developmental exam findings consistent with late infantile Krabbe disease 3. Participants must be considered candidates for HSCT or have received HSCT at least 21 days prior to dosing date 4. For patients already transplanted and followed for more than 3 months chimerism should reflect at least 30% of myeloid cells from the donor by month 3 post-transplant, from 30 to 10% between 3 months and one year post-transplant or 10% by one year post-transplant. 5. Participant must have adequate organ function at time of screening or evaluation as measured by: 1. Ejection fraction of \> 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension. 2. Pulmonary evaluation testing demonstrating resting pulse oximeter \> 95% on room air. 6. Absence of active aspiration 7. Participant's parents or legal guardian consent to participate in the study and provide informed consent according to IRB/IEC guidelines prior to any study procedures being performed 8. Parent(s) and/or legal guardian able to comply with the clinical protocol Exclusion Criteria: 1. Immunoassay with total anti-AAV10 antibody titers of \>1:100. This criterion will not apply to children screened before they have received HSCT or for children who sign the inform consent within 6 months from HSCT. In children who test positive to anti-AAV10 antibody with titers of \>1:100 under this exception, the ISR regime proposed by the PI and approved/modified by the ISR committee may include immunosuppressive drugs that prevent the potential development of a secondary immune response to AAVrh10 after FBX-101 administration. 2. History of prior treatment with a gene therapy product 3. Motor function evaluated by age with PDMS-II by a study physical therapist: a. Inability to hold head for patients older than 5 months; b. Inability to sit independently for patients older than 12 months; c. Inability to walk with assistance for patients older than 24 months. 4. In patients that sign the informed consent before HSCT or up to 90 days post-HSCT, abnormalities in white count, hemoglobin and platelets found from conditioning regime to Day -1 (the day before FBX-101 administration) will be evaluated by the PI (with referral to the DSMB if indicated). If abnormal, they will not be considered an exclusion criteria if the PI considers they are consistent with expected consequences of the HSCT (and related management) and upon confirmation they were not present before commencement of the conditioning regime. 5. Grade 2 or higher abnormalities in LFTs, bilirubin, creatinine, white count, hemoglobin, platelets, PT/INR and PTT according to latest version of CTCAE 6. Presence of any neurocognitive deficit, motor deficit, or brain damage not attributable to Krabbe disease 7. Signs of active infections or disease from cytomegalovirus, adenovirus, EBV, hepatitis B or C, and HIV or other viruses excluding rhinovirus from RVP and asymptomatic norovirus presence in stool. Patients showing HIV positive results will be excluded from the study. 8. Active bacterial or fungal infection documented the preceding 7 days. 9. Presence of any contraindication for MRI or lumbar puncture (LP) 10. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions 11. Immunizations with live viruses in the 30 days prior to immune suppression 12. Active acute Graft Versus Host Disease (GvHD) Grade II or higher according to modified Glucksberg criteria (Przepiorka et al., 1995) or active, moderate or severe, chronic GvHD according to revised NIH criteria (Jagasia et al., 2015) 13. Any other medical condition, serious intercurrent illness, other genetic condition or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study