Study of the Safety and Efficacy of an Adeno-Associated Viral Vector Carrying the SMN Gene After a Single Intravenous Administration of Escalating Doses in Children With Spinal Muscular Atrophy (BLUEBELL) (BLUEBELL)
Spinal Muscular Atrophy (SMA)
About this trial
This is an interventional treatment trial for Spinal Muscular Atrophy (SMA)
Eligibility Criteria
Inclusion Criteria: Informed consent form for participation in the study signed by the subject's legal representative; Subjects of either sex under the age of 240 days at the time of signing the Information Sheet for the Legal Representative of the Clinical Study Subject with Informed Consent Form; A diagnosis of 5q-SMA established clinically and confirmed by molecular genetic testing (homozygous deletion of exon 7 of the SMN1 gene or heterozygous deletion of exon 7 + confirmed point mutation of the SMN1 gene) and 2 copies of the SMN2 gene, with an age of onset up to 180 days from birth; The ability of the subject's legal representative, in the Investigator's opinion, to perceive information and follow the Protocol procedures. Exclusion Criteria: A diagnosis of HIV infection, hepatitis B, hepatitis C, congenital syphilis in the study subject, as well as a documented diagnosis of HIV infection in the study subject's mother. Note: documented hepatitis B and/or hepatitis C and/or syphilis in the mother of a study subject is not an exclusion criterion in this clinical study, provided that standard breastfeeding rules are followed or the subject is not breastfed due to the low risk of transmission of hepatitis B and C viruses and Treponema pallidum from mother to child with breast milk; Unwillingness of the legal representative to use alternative feeding methods (nasogastric tube, gastrostomy) in case of swallowing disorders and a risk of aspiration; Anti-AAV9 antibody titer >1:50 determined by ELISA. Note: if a subject's screening anti-AAV9 antibody titer is >1:50, the anti-AAV9 antibody titer may be determined again. Subjects with anti-AAV9 antibody titers ≤1:50 in the second test may be included in the study; Need for respiratory support for ≥16 hours per day or tracheostomy ; Treatment with nusinersen, risdiplam, branaplam, onasemnogene abeparvovec or other antisense oligonucleotides/selective SMN2 splicing modifiers or gene therapy drugs for SMN1 transduction or other AAV-based gene therapy drugs regardless of serotype used previously (from birth) or planned for the main study period, i.e., within 12 months after the administration of the investigational product. A need to use any medications for the treatment of myopathy or neuropathy, drugs for the treatment of diabetes, ongoing immunosuppressive therapy, or the need for immunosuppressive therapy after the start of the study (for example, glucocorticoids (except for premedication and post-medication), cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc.); Subjects with the following laboratory test results at screening: increased activity of transaminases (ALT, AST) or GGT >2×ULN; total bilirubin level ≥34 µmol/L; creatinine level ≥160 µmol/L; hemoglobin <80 g/L and >180 g/L; WBC count >20x109/L; Troponin I level > ULN. Any concomitant diseases that, in the Investigator's opinion, may affect the safety of ANB-004 in the subject or have a significant impact on the assessment of the outcomes of SMA therapy; A diagnosis of acute or chronic hepatic failure at screening; A known allergy or intolerance to any components of the investigational product or pre- and post-medication drug (glucocorticoids); Simultaneous participation of the subject in other clinical studies or previous participation in another clinical study using an experimental therapy.
Sites / Locations
- State Autonomous Healthcare Institution Sverdlovsk Regional Children's Clinical HospitalRecruiting
- Federal State Autonomous Educational Institution of Higher Education "Pirogov Russian National Research Medical University" of the Ministry of Heathcare of the Russian Federation. Children's clinical hospital.Recruiting
- Federal State Autonomous Educational Institution of Higher Education "Pirogov Russian National Research Medical University" of the Ministry of Heathcare of the Russian FederationRecruiting
- National Medical Research Center for Children's Health" of the Ministry of Healthcare of the Russian FederationRecruiting
- Federal State budgetary Educational Institution of Higher Education "St. Peterburg State Pediatric Medical University" of the Ministry of Heathcare of the Russian FederationRecruiting
- Federal State Budgetary Institution "Almazov National Medical Research Centre" of the Ministry of Health of the Russian FederationRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort 1
Cohort 2
Cohort 3
Subjects in Cohort 1 will receive ANB-004 at a dose 1. Depending on the DLT, the cohort may include 1 to 6 subjects in the first stage and 9 to 12 in the second stage.
Subjects in Cohort 2 will receive ANB-004 at a dose 2. The dose for Cohort 2 will be determined at the IDMC meeting. Depending on the DLT, the cohort may include 1 to 6 subjects in the first stage and 9 to 12 in the second stage.
Subjects of Cohort 3, if included, will receive the drug at a dose 3. The dose for Cohort 3 will be determined at the IDMC meeting. Depending on the DLT, the cohort may include 1 to 6 subjects in the first stage and 9 to 12 in the second stage.