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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02716246




Registration number
NCT02716246
Ethics application status
Date submitted
17/03/2016
Date registered
23/03/2016

Titles & IDs
Public title
Phase I/II/III Gene Transfer Clinical Trial of ScAAV9.U1a.hSGSH
Scientific title
Phase I/II/III Gene Transfer Clinical Trial of ScAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
Secondary ID [1] 0 0
UX111-CL301
Secondary ID [2] 0 0
ABT-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MPS IIIA 0 0
Sanfilippo Syndrome 0 0
Sanfilippo a 0 0
Mucopolysaccharidosis III 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - UX111
Treatment: Drugs - Adjuvant IM Therapy

Experimental: Cohort 1 Low Dose - Dose of 0.5 X 10\^13 vg/kg

Experimental: Cohort 2 Mid Dose - Dose of 1 X 10\^13 vg/kg

Experimental: Cohort 3 High Dose - Dose of 3 X 10\^13 vg/kg

Experimental: Cohort 4 High Dose (Spain Only) - Dose of 3 X 10\^13 vg/kg


Treatment: Other: UX111
Self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the control of a U1a promoter (scAAV9.U1a.hSGSH) will be delivered one time through a venous catheter inserted into a peripheral limb vein.

Treatment: Drugs: Adjuvant IM Therapy
The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IM therapy. Not all participants may receive adjuvant IM therapy.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) (Disaccharide) Exposure
Timepoint [1] 0 0
Up to Month 24 Visit
Secondary outcome [1] 0 0
Bayley Scales of Infant and Toddler Development-Third Edition (BSITD-III) Cognitive Raw Score Over Time
Timepoint [1] 0 0
Up to Month 24 Visit
Secondary outcome [2] 0 0
CSF Ganglioside Type 2 (GM2) Exposure
Timepoint [2] 0 0
Up to Month 24 Visit
Secondary outcome [3] 0 0
CSF Ganglioside Type 3 (GM3) Exposure
Timepoint [3] 0 0
Up to Month 24 Visit
Secondary outcome [4] 0 0
Percent Change from Baseline in CSF HS
Timepoint [4] 0 0
Baseline, Up to Month 24 Visit
Secondary outcome [5] 0 0
BSITD-III Receptive Communication Raw Score Over Time
Timepoint [5] 0 0
Up to Month 24 Visit
Secondary outcome [6] 0 0
BSITD-III Expressive Communication Raw Score Over Time
Timepoint [6] 0 0
Up to Month 24 Visit
Secondary outcome [7] 0 0
Percent Change From Baseline in Total Cortical Volume
Timepoint [7] 0 0
Baseline, Up to Month 24 Visit

Eligibility
Key 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 (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
* Age:

* For Cohort 1-3: From birth (participating sites in USA and Australia) OR 6 months (participating sites in Spain) to 2 years of age with no BSITD-III Cognitive Development Quotient (DQ) requirement, or older than 2 years with a BSITD-III Cognitive DQ of 60 or above (participating sites globally).
* For Cohort 4 (participating sites in Spain): 3 months to = 2 years of age with no BSITD-III Cognitive DQ requirement, or > 2 years of age with a BSITD-III Cognitive DQ of 60 or above, or > 2 years and = 5 years of age with a BSITD-III Cognitive DQ < 60
* Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Screening as verified by documentation from the subject's primary care physician, and willing to defer vaccines through 6 months after completion of the subject's IM medication, or longer per Principal Investigator (PI) judgment. Emergency use authorization of coronavirus disease (COVID) vaccines is included unless there is an accepted medical exemption.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability to participate in the clinical evaluation as determined by PI
* Identification of two nonsense or null variants on genetic testing of the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
* At least one S298P mutation in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
* Has evidence of an attenuated phenotype of MPS IIIA, in the judgement of the PI
* 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
* Cohorts 1-3 only: Subjects with total anti-AAV9 antibody titers = 1:100 equivalent to a positive screen as determined by ELISA in serum, Cohort 4: Subjects testing positive for total anti-AAV9 antibodies as determined at Screening
* Cohorts 1-3 only: Subjects with a positive response for the enzyme-linked immunosorbent spot (ELISpot) for T-cell responses to AAV9
* Cohorts 1-3 only: Serology consistent with exposure to human immunodeficiency virus (HIV), or serology consistent with active hepatitis B or C infection, Cohort 4: Current clinically significant infections (including any requiring systemic treatment including, but not limited to, HIV; hepatitis A, B, or C; varicella zosters virus; human T-cell lymphotropic virus type 1 [HTLV-1]; tuberculosis; or COVID-19) that would interfere with participation in the study.
* 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, hearing, or other impairment sufficient to preclude cooperation with neurodevelopmental testing
* Uncontrolled seizure disorder
* Any item (braces, etc.) or circumstance 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
* Cohorts 1-3: Abnormal laboratory values Grade 2 or higher as defined in common terminology criteria for adverse events (CTCAE) v4.03 for gamma-glutamyl transferase (GGT), total bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT) and activated partial thromboplastin time (aPTT), Cohort 4: Any of the following abnormal laboratory values from screening assessment:

* Aspartate aminotransferase (AST), alanine aminotransaminase (ALT), and/or GGT and/or alkaline phosphatase = 2 × upper limit of normal (ULN) and/or total bilirubin > 1.5 × ULN
* Anemia (hemoglobin < 10 g/dL)
* Leukopenia or leukocytosis (total WBC count < 3,000/mm3 and > 15,000/mm3 respectively)
* Abnormal absolute neutrophil count (ANC) of < 1000/mm3
* Platelet count < 100,000/mm3
* Coagulopathy (international normalized ratio [INR] > 1.5) or aPTT > 40 seconds
* Renal impairment, defined as estimated glomerular filtration rate (eGFR) below the lower limit of normal (age and sex appropriate) based on Bedside Schwartz equation
* Female of childbearing potential who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable)
* Cohorts 1-3: 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

Cohort 4 only:

* Known hypersensitivity, that in the judgment of the PI, places the subject at increased risk for adverse effects.
* Willing to avoid consumption of grapefruit juice and the use of strong inhibitors of CYP3A4 and/or P-gp (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin), strong inducers of CYP3A4 and/or P-gp (eg, rifampin, rifabutin, phenobarbital, carbamazepine, or phenytoin), or St. John's Wort 30 days prior to Screening and until completion of the sirolimus regimen, due to potential interaction with sirolimus.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Ohio
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Spain
State/province [3] 0 0
Barcelona
Country [4] 0 0
Spain
State/province [4] 0 0
Santiago De Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ultragenyx Pharmaceutical Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Abeona Therapeutics, Inc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patients Contact: Trial Recruitment
Address 0 0
Country 0 0
Phone 0 0
1-888-756-8657
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02716246