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

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ClinicalTrials.gov Identifier: NCT04088734
Recruitment Status : Not yet recruiting
First Posted : September 13, 2019
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Abeona Therapeutics, Inc

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

Condition or disease Intervention/treatment Phase
MPS IIIA Sanfilippo Syndrome Sanfilippo A Mucopolysaccharidosis III Drug: ABO-102 Phase 1 Phase 2

Detailed Description:
This is a open-label, single dose clinical trial. All participants will receive 3 X 10^13 vg/kg of ABO-102 delivered one time through a venous catheter inserted into a peripheral limb vein. The target population includes MPS IIIA participants with a DQ lower than 60 in middle and advanced phases of the disease. Similar numbers of MPS IIIA participants with age equivalent above and below 18 months of age will be enrolled to ensure a representation of middle and advanced phases of the disease.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Open Label, Single-dose, Gene Transfer Study of scAAV9.U1a.hSGSH (ABO-102) in Patients With Middle and Advanced Phases of MPS IIIA Disease
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: ABO-102 Drug: ABO-102
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
Other Name: scAAV9.U1a.hSGSH




Primary Outcome Measures :
  1. Adverse Events and Serious Adverse Events [ Time Frame: 24 months ]
    The incidence, type, and severity of treatment-related adverse events and serious adverse events

  2. CSF Heparan Sulfate [ Time Frame: 1, 6, 12, 24 months ]
    Change from baseline in CSF heparan sulfate levels after treatment

  3. Liver and/or Spleen Volumes [ Time Frame: 1, 6, 12, 24 months ]
    Change from baseline in liver and/or spleen volumes after treatment, as measured by MRI


Secondary Outcome Measures :
  1. Glycosaminoglycans or Heparan Sulfate [ Time Frame: 1, 6, 12, 18, 24 months ]
    Change from baseline in plasma or urine glycosaminoglycans or heparan sulfate after treatment

  2. SGSH Enzyme Activity [ Time Frame: 1, 6, 12, 24 Months ]
    Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment

  3. Brain Volume [ Time Frame: 1, 6, 12, 24 months ]
    Change from baseline in brain volume after treatment, as measured by MRI

  4. Developmental Age [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in the Developmental Age after treatment compared to Natural History Study data calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, 2nd edition, based on chronological and developmental age

  5. Cognitive Developmental Age [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in the Cognitive Developmental Age after treatment compared to Natural History Study, calculated using the Bayley Scales of Infant and Toddler Development - Third edition or the Kaufman Assessment Battery for Children. Second Edition, based on developmental age

  6. Adaptive Age Equivalent Score [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in the Adaptive Age Equivalent score after treatment compared to Natural History Study data, as assessed by parent report using the Vineland Adaptive Behavior Scale II Survey form

  7. Sanfilippo Behavior Rating Scale [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in the Sanfilippo Behavior Rating Scale

  8. Sleep Pattern [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in sleep pattern as measured by the modified Children's Sleep Habits Questionnaire (CSHQ)

  9. Pediatric Quality of Life Inventory [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales total score

  10. Parent Quality of Life [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)

  11. Gastrointestinal Symptoms [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in gastrointestinal symptoms using the PedsQL™ Gastrointestinal Symptoms Scales

  12. Parent Global Impression Score [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in Parent Global Impression Score

  13. Clinical Global Impression Improvement Scale [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in Clinical Global Impression Improvement Scale

  14. Parent Symptoms Score Questionnaire [ Time Frame: 6, 12, 18, 24 months ]
    Change from baseline in Parent Symptoms Score Questionnaire

  15. Body Mass Index [ Time Frame: 6, 12, 18, 24 months ]
    Change from Baseline in Body Mass Index after treatment

  16. EEG Monitoring [ Time Frame: 6, 12, 18, 24 months ]
    Incidence and Change from baseline in abnormalities in standard awake 60-minutes- EEG monitoring

  17. AAV9 Viral DNA Detection [ Time Frame: 24 months ]
    Detection of the AAV9 viral DNA in plasma, saliva, urine and feces will be performed until two consecutive samples are negative



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of MPS IIIA confirmed by the following methods:

    1. No detectable or significantly reduced SGSH enzyme activity by leukocyte assay
    2. 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

Exclusion Criteria:

  • Inability to participant 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
  • 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 v4.0 for GGT, total bilirubin (except in subjects diagnosed with Gilbert's syndrome), creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
  • Female participant who is pregnant or demonstrates a positive urine or beta-hCG 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 Haematopoietic Stem Cell transplantation
  • Previous participation in a gene/cell therapy or ERT clinical trial
  • Participants who are anticipated to undergo a procedure involving anesthesia within 6 months post- drug administration
  • Dysphagia present at Grade 3 or higher, as defined in CTCAE v4.0

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04088734


Contacts
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Contact: Medical Affairs +34 689 166 070 sanfilippo@abeonatherapeutics.com

Locations
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United States, Pennsylvania
Children's Hospital of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Maria L Escolar, MD, MS    412-692-6350    maria.escolar@chp.edu   
Principal Investigator: Maria L Escolar, MD, MS         
Australia, South Australia
Adelaide Women's and Children's Hospital Not yet recruiting
North Adelaide, South Australia, Australia, 5006
Contact: Louise Jaensch    08 8161 7295    louise.jaensch@sa.gov.au   
Principal Investigator: Nicholas Smith, MD, PhD         
Spain
Hospital Clínico Universitario de Santiago Not yet recruiting
Santiago De Compostela, Spain, 15706
Contact: Maria Luz Couce, MD, PhD       maria.luz.couce.pico@sergas.es   
Contact: Maria Jose de Castro, MD, PhD    +34 981 955 040    maria.jose.de.castro.lopez@sergas.es   
Principal Investigator: Maria Luz Couce, MD, PhD         
Sponsors and Collaborators
Abeona Therapeutics, Inc
Investigators
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Principal Investigator: Maria L Escolar, MD, MS UPMC Children's Hospital of Pittsburgh
Principal Investigator: Nicholas Smith, MD, PhD Adelaide Women's and Children's Hospital
Principal Investigator: Maria Luz Couce, MD Hospital Clinico Universitario de Santiago

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Responsible Party: Abeona Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT04088734     History of Changes
Other Study ID Numbers: ABT-003
First Posted: September 13, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abeona Therapeutics, Inc:
MPS IIIA
Sanfilippo
Gene therapy
Additional relevant MeSH terms:
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Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases