Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH

Ultragenyx

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Sanfilippo A; MPS IIIA; Mucopolysaccharidosis III; Sanfilippo Syndrome

Treatments: Biological: ABO-102; Drug: Adjuvant Immunosuppression (IS) Therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT02716246

ABT001

2015-003904-21 (EudraCT Number)

UX111-CL301 (Other Identifier)

Details and patient eligibility

About

The main objective of this study is to evaluate the efficacy and safety of ABO-102 for the treatment of MPS IIIA.

Full description

Open-label, single dose, dose-escalation clinical trial of ABO-102 (scAAV9.U1a.hSGSH) injected intravenously through a peripheral limb vein. A tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least three months. At approved sites immunosuppression (IS) therapy may be administered to selected participants. The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IS therapy. Not all participants may receive IS therapy.

This study was previously posted by Abeona Therapeutics, Inc and was transferred to Ultragenyx in August 2022.

Enrollment: 28 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of MPS IIIA confirmed by the following methods:

  • No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and
  • Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene

• Age: From birth to 2 years or children older than 2 years with a minimum cognitive Developmental Quotient (DQ) of 60 or above (calculated by Bayley Scales of lnfant and Toddler Development - Third Edition)

Exclusion criteria

• Inability to participate in the clinical evaluation as determined by Principal Investigator (PI)
• Identification of two nonsense or null variants on genetic testing of the SGSH gene
• At least one S298P mutation in the SGSH gene
• Has evidence of an attenuated phenotype of MPS IIIA
• Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
• Active viral infection based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer or precludes the child from participating in the protocol assessments and follow up
• Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by ELISA in serum
• Subjects with a positive response for the enzyme-linked immunosorbent spot (ELISpot) for T-cell responses to AAV9
• Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection
• Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy
• Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing
• Uncontrolled seizure disorder
• Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy
• Any other situation that precludes the subject from undergoing procedures required in this study
• Subjects with cardiomyopathy or significant congenital heart abnormalities
• The presence of significant non-MPS IlIA related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.03 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
• Female participant who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable)
• Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
• Previous treatment by Hematopoietic Stem Cell transplantation
• Previous participation in a gene/cell therapy or enzyme replacement therapy (ERT) clinical trial

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

28 participants in 3 patient groups

Cohort 1 Low Dose

Experimental group

Description:

Dose of 0.5 X 10\^13 vg/kg

Treatment:

Drug: Adjuvant Immunosuppression (IS) Therapy

Biological: ABO-102

Cohort 2 Mid Dose

Experimental group

Description:

Dose of 1 X 10\^13 vg/kg

Treatment:

Drug: Adjuvant Immunosuppression (IS) Therapy

Biological: ABO-102

Cohort 3 High Dose

Experimental group

Description:

Dose of 3 X 10\^13 vg/kg

Treatment:

Drug: Adjuvant Immunosuppression (IS) Therapy

Biological: ABO-102