2023-510032-37-00招募中2 期
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Safety: Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
研究概览
简要总结
To evaluate the efficacy and safety of UX111 (also known as ABO-102) for the treatment of mucopolysaccharidosis (MPS) IIIA
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Open-label, Single Injection Ascending Dose Study
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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:
- •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 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
结局指标
主要结局
Safety: Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
Safety: Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
Efficacy: Cerebrospinal fluid (CSF) heparan sulfate (HS) (disaccharide) exposure
Efficacy: Cerebrospinal fluid (CSF) heparan sulfate (HS) (disaccharide) exposure
次要结局
- Bayley Scales of Infant and Toddler Development–Third edition (BSITD- III) Cognitive raw score
- CSF ganglioside type 2 (GM2) exposure
- CSF ganglioside type 3 (GM3) exposure
- CSF HS percentage change from baseline
- BSITD-III Receptive Communication raw score
- BSITD-III Expressive Communication raw score
- Total cortical volume (cm 3) percentage change from baseline
研究者
Medical Information
Scientific
Ultragenyx Pharmaceutical Inc.
研究点 (2)
Loading locations...
相似试验
招募中
1 期
FusionVAC22_02: DNAJB1-PRKACA fusion transcript-based peptide vaccine for fibrolamellar hepatocellular carcinoma patients and other tumor entities carrying the oncogenic driver fusion2024-519387-41-00Universitaetsklinikum Tuebingen AöR20
招募中
3 期
GRAVITI - A Phase 3 Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants with Moderately to Severely Active Crohn's Disease2023-504737-41-00Janssen - Cilag International219
招募中
3 期
Study to Evaluate the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of Subcutaneously Administered Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis2023-507144-36-00Janssen - Cilag International30
尚未招募
1 期
A Phase 1 Comparative Study to Evaluate Pharmacokinetics, Immunogenicity, Safety and Tolerability of Bmab3000 and Herceptin Hylecta® After a Single 600 mg SC Injection in Healthy Male VolunteersNCT07299955Biocon Biologics UK PLC150
进行中（未招募）
3 期
Safety, Tolerability, and Immunogenicity of VAX-31 in Adults ≥50 Years With Immunobridging to Adults 18-49NCT07284654Vaxcyte, Inc.4,049