Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease

NCT04088734 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: ABT-003UX111-CL2012018-000504-42
• Study Type: interventional
• Target: 5
• Locations: 3 countries
• Sites: 3

Brief Summary

Open-label, clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein

Conditions

MPS IIIA; Sanfilippo Syndrome; Sanfilippo A; Mucopolysaccharidosis III

Keywords

MPS IIIA; Sanfilippo; Gene therapy

Outcome Measures

Primary Outcomes (4)

• Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame

  An adverse event (AE) is any untoward medical occurrence or unintended change from the time informed consent form (ICF) is signed, including inter-current illness that occurs during the course of a clinical trial after treatment has started, whether considered related to treatment or not. TEAEs are those that occurred after the start of study drug. Related adverse events were categorized as possible, probable, or definitely.

  From the first dose of study drug to <30 days postdose, Day 30, 60, 90, 180 and Month 12

• Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame

  An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations such as important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. Relationship to study drug was defined as unrelated, unlikely, possible, probable, or definitely.

  From signing of informed consent through Day 60, 90, 180 and up to Day 454 (> 12 months)

• Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment

  As Measured by Magnetic Resonance Imaging (MRI). Baseline value of multiple of normal is calculated using the baseline values of the Liver volume/Spleen Volume/Height and Weight. * Body Surface Area (BSA) (m2)=( Height(cm) \* Weight (kg)/3600)1/2. * Normal Liver Volume=(689.9 \* BSA (m)) - 24.7. * Normal Spleen Volume (mL)=(4.6 \* Weight (kg)) + 0.7. * Liver Volume (multiples of normal)=Subject Liver Volume (mL)/Normal Liver Volume (mL). * Spleen Volume (multiples of normal)=Subject Spleen Volume (mL)/Normal Spleen Volume (mL).

  Baseline, Day 30, 180, Month 12

• Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment

  Change from baseline in CSF heparan sulfate levels after treatment

  Baseline, Day 30, Day 180, Month 12

Secondary Outcomes (18)

• Change From Baseline in Plasma Heparan Sulfate After Treatment

  Baseline, Day 30, Day 180, Month 12

• Change From Baseline in Urine Glycosaminoglycans After Treatment

  Baseline, Day 30, Day 180, Month 12

• Change From Baseline in Urine Heparan Sulfate After Treatment

  Baseline, Day 30, Day 180, Month 12

• Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment

  Baseline, Day 30, Day 180, and Month 12

• Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment

  Baseline, Day 30, Day 180, Month 12

Study Arms (1)

ABO-102

EXPERIMENTAL

Dose of 3x10\^13 vg/kg

Drug: ABO-102

Interventions

ABO-102 DRUG

Single dose of ABO-102 (scAAV9.U1a.hSGSH) administered by intravenous injection through a peripheral limb vein at a dose of 3 X 10\^13 vg/kg

Also known as: scAAV9.U1a.hSGSH, UX111

ABO-102

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Cognitive Development Quotient (DQ) lower than 60 (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)
• Must be ambulatory, though may receive assistance with ambulation
• Age range of 2 years up to 18 years (excluded)

You may not qualify if:

• Inability to participate in the clinical evaluation as determined by Principal Investigator
• 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
• Participants with total anti-AAV9 antibody titers greater than or equal to 1:100 as determined by ELISA binding immunoassay
• Participants with a positive response for the 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
• Any item (braces, etc.) which would exclude the participant from being able to undergo MRI according to local institutional policy
• Any other situation that precludes the participant from undergoing procedures required in this study
• Participants with cardiomyopathy or significant congenital heart abnormalities

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead
• Abeona Therapeutics, Inc: collaborator

Study Sites (3)

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Adelaide Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Hospital Clínico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Related Publications (2)

• Fu H, Cataldi MP, Ware TA, Zaraspe K, Meadows AS, Murrey DA, McCarty DM. Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery. Mol Ther Methods Clin Dev. 2016 Jun 8;3:16036. doi: 10.1038/mtm.2016.36. eCollection 2016.

  PMID: 27331076 BACKGROUND

• Fu H, Meadows AS, Pineda RJ, Kunkler KL, Truxal KV, McBride KL, Flanigan KM, McCarty DM. Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy. Hum Gene Ther Clin Dev. 2017 Dec;28(4):187-196. doi: 10.1089/humc.2017.109. Epub 2017 Oct 24.

  PMID: 29064732 BACKGROUND

MeSH Terms

Conditions

Mucopolysaccharidosis III

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: September 18, 2019
• Primary Completion: March 10, 2022
• Study Completion: March 10, 2022
• Last Updated: July 25, 2023
• Results First Posted: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); AU (1); ES (1)