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Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
EU CTIS ID: 2023-510032-37-00
What this study is testing
To evaluate the efficacy and safety of UX111 (also known as ABO-102) for the treatment of mucopolysaccharidosis (MPS) IIIA
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Diagnosis of MPS IIIA confirmed by the following methods:a. No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and b) 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 Cohorts 1 to 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 at Screening Visit 1 (n = up to 6). Up to 2 additional subjects > 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ < 60 may also be enrolled. • Subjects must be ≥ 3 months of age before any screening assessments or procedures are performed. • For children ≤ 24 months chronological age who were born prematurely, defined as born at < 36 weeks gestational age, the corrected gestational age must be used for determining inclusion. • The BSITD-III Cognitive DQ is assessed during the onsite Screening visit. • The age of the child on the date of the Screening BSITD-III assessment is used to determine the requirement for the BSITD-III Cognitive DQ score.
- Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Enrollment 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.
You likely can't join if
- Inability to participate in the clinical evaluation as determined by PI
- Cohorts 1 to 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: 1. 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 2. Anemia (hemoglobin < 10 g/dL) 3. Leukopenia or leukocytosis (total WBC count < 3,000/mm3 and > 15,000/mm3 respectively) 4. Abnormal absolute neutrophil count (ANC) of < 1000/mm3 5. Platelet count < 100,000/mm3 6. Coagulopathy (international normalized ratio [INR] > 1.5) or aPTT > 40 seconds 7. 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 β-human chorionic gonadotropin (hCG) result at screening assessment (if applicable)
- Cohorts 1 to 3 only: 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)
- Cohorts 1 to 3 only: 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
See the full eligibility criteria
Who can join
- Diagnosis of MPS IIIA confirmed by the following methods:a. No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and b) 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 Cohorts 1 to 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 at Screening Visit 1 (n = up to 6). Up to 2 additional subjects > 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ < 60 may also be enrolled. • Subjects must be ≥ 3 months of age before any screening assessments or procedures are performed. • For children ≤ 24 months chronological age who were born prematurely, defined as born at < 36 weeks gestational age, the corrected gestational age must be used for determining inclusion. • The BSITD-III Cognitive DQ is assessed during the onsite Screening visit. • The age of the child on the date of the Screening BSITD-III assessment is used to determine the requirement for the BSITD-III Cognitive DQ score.
- Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Enrollment 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.
What rules you out
- Inability to participate in the clinical evaluation as determined by PI
- Cohorts 1 to 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: 1. 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 2. Anemia (hemoglobin < 10 g/dL) 3. Leukopenia or leukocytosis (total WBC count < 3,000/mm3 and > 15,000/mm3 respectively) 4. Abnormal absolute neutrophil count (ANC) of < 1000/mm3 5. Platelet count < 100,000/mm3 6. Coagulopathy (international normalized ratio [INR] > 1.5) or aPTT > 40 seconds 7. 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 β-human chorionic gonadotropin (hCG) result at screening assessment (if applicable)
- Cohorts 1 to 3 only: 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)
- Cohorts 1 to 3 only: 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 clinical trial.
- 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 judgment of the PI
- Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
- Active viral infection based on clinical observations (see also exclusion criterion #10)
- Cohorts 1 to 3: 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.
- 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 to 3 only: Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by enzyme-linked immunosorbent assay (ELISA) binding assay in serum
- Cohorts 1 to 3 only: Subjects with a positive response for the enzyme-linked immunospot assay (ELISpot) for T-cell responses to AAV9
- Known hypersensitivity to UX111 or its excipients, rituximab, sirolimus, prednisone or prednisolone, bortezomib (as applicable), eculizumab, proton pump inhibitors, H2 antagonists, or peanut or soya that, in the judgment of the PI, places the subject at increased risk for adverse effects.
- Unwilling 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), and St. John’s Wort from 30 days prior to Screening through completion of the sirolimus and bortezomib (as applicable) regimens, due to potential interaction with sirolimus or bortezomib (as applicable).
- Bleeding disorder or any other medical condition or circumstance in which a LP (for collection of CSF) is contraindicated according to local institutional policy
- Visual, hearing, or other impairment sufficient to preclude cooperation with neurodevelopmental testing in the judgment of the PI
- Uncontrolled seizure disorder
- Any item (braces, etc.) or circumstance which would exclude the subject from being able to undergo magnetic resonance imaging (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
- Thepresence of significant non-MPS IIIA related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
The study team makes the final eligibility decision.
Where it's taking place
- Australia
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Australia; United States. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.