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Report for Clinical Trial NCT04201405

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I-II, Study of Autologous CD34+ Haematopoietic Stem Cells Transduced ex Vivo With CD11b Lentiviral Vector Encoding for Human SGSH in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIa, Sanfilippo Syndrome Type A)

Patients with MPS IIIA have a clinical disorder marked by severe and progressive brain disease and neurological symptoms due to the accumulation of undigested glycosaminoglycans in all cells of the body. This study will be the first in human clinical trial to explore the safety, tolerability and clinical efficacy of ex vivo gene therapy (autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene) in MPSIIIA patients. Following treatment with the gene therapy patients will be followed up for a minimum of 3 years.

NCT04201405 Mucopolysaccharidosis Type IIIA
MeSH:Mucopolysaccharidoses Mucopolysaccharidosis III

1 Interventions

Name: Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene

Description: Autologous CD34+ haematopoietic stem cells from MPS IIIA patients will be genetically modified ex vivo using CD11b.SGSH Lentiviral vector (LV), a self-inactivating LV expressing the SGSH gene codon optimized for human use and regulated by a human CD11b myeloid-specific promoter. Cells will be cryopreserved prior to patient administration.
Type: Drug
Group Labels: 1

Haematopoietic stem cell gene therapy for MPS IIIA


Primary Outcomes

Description: Adverse events will be recorded and graded according to an adapted Pediatric Clinical Toxicity Scale from the National Institute Allergy and Infectious Diseases (NIAID), Autoimmuno-deficiency Syndrome (AIDS) Division

Measure: To evaluate the tolerability of the IMP in MPS IIIA patients: scale

Time: up to 3 years

Description: Measured by the expression of SGSH in total leukocytes within or above normal range at 12 months post-IMP treatment

Measure: To evaluate the biological efficacy of IMP post-treatment: expression of SGSH in total leukocytes

Time: 12 months post gene therapy

Description: Presence of replication competent virus and integration events in the leukocytes

Measure: To assess the safety of the IMP in MPS IIIA patients

Time: up to 3 years

Secondary Outcomes

Description: Overall survival at 36 months post IMP administration compared to natural history data

Measure: To evaluate overall survival

Time: up to 3 years

Description: Measured as absence of engraftment failure or delayed hematological reconstitution within the first 6 weeks of IMP delivery. Defined as three independent and consecutive days with absolute Neutrophil Count (ANC) >500/mm3 and/or Platelets >20,000/mm3 without transfusions, and/or Hb >8.0 g/dL without transfusions.

Measure: To evaluate peripheral engraftment of the IMP

Time: within 42 days of treatments

Description: Measured using the Vineland Adaptive Behaviour scales against natural history of MPSIIIA

Measure: Change in adaptive behaviour

Time: up to 3 years (multiple visits)

Description: Measurement of cognitive score (standard scores, age equivalent scores and development quotient) using the Bayley Scales of Infant Development, 3rd Edition [BSID-III] or Kaufman Assessment Battery for Children, 2nd Edition [KABC-II] against natural history of MPSIIIA

Measure: Change in cognitive function

Time: up to 3 years (multiple visits)

Description: Measured using the Sanfilippo Behaviour Rating Scale against natural history of MPSIIIA

Measure: Change in patient behaviour

Time: up to 3 years

Description: Measured using the Infant Toddler Quality of Life questionnaire against natural history of MPSIIIA

Measure: Change in patient quality of life

Time: Up to 3 years

Description: Measured using the Children sleep Questionnaire against natural history data

Measure: Change in patient's daily living

Time: Up to 3 years

Other Outcomes

Description: Measure change in ng/ml glycosaminoglycans in CSF from baseline following IMP administration

Measure: To evaluate the effect of the IMP on heparan sulphate concentration in cerebrospinal fluid (CSF), plasma and urine

Time: 6 months and 12 months post-IMP treatments and multiple other visits over time

Description: Change in SGSH activity measured from baseline

Measure: To evaluate the effect of the IMP on SGSH activity in CSF, plasma and peripheral blood mononuclear cells.

Time: 6 months and 12 months post-IMP treatments and multiple other visits over time

Description: Measure change in brain volume (total brain, greey and white matter, ventricle volume) by MRI and compare to baseline and natural history data to help assess brain development

Measure: To evaluate clinical efficacy of the IMP on brain imaging biomarkers

Time: up to 3 years

Description: Measure whether an immune response is generated against the SGSH enzyme

Measure: To explore the presence of anti-SGSH antibodies following treatment with the IMP

Time: up to 3 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 S298P

5. Homozygous or compound heterozygous for the S298P mutation or any other mutation known to be associated to slow-progressing phenotype. --- S298P ---



HPO Nodes