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)
NCT ID: NCT05747261
Last Updated: 2024-02-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
40 participants
INTERVENTIONAL
2023-02-02
2030-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
NCT04851873
Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies
NCT06532474
Single-Dose Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1
NCT03461289
A Study to Learn About the Safety of BIIB115 Injections and How BIIB115 is Processed in the Bodies of Healthy Adult Male Volunteers and of Pediatric Participants With Spinal Muscular Atrophy Who Previously Took Onasemnogene Abeparvovec
NCT05575011
Study of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1
NCT07070999
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Stage 1: pilot efficacy and safety study of different doses to select a potentially therapeutic dose for further study.
Stage 2: study of the efficacy and safety of ANB-004 at the selected potentially therapeutic dose.
At the first stage, the study will have a "3+3" design and involve dose escalation in two cohorts, with the possibility of including a third cohort. Three subjects are to be included in each cohort, each of whom will receive a pre-specified cohort dose of ANB-004 as a single intravenous infusion.
Subjects will be monitored for dose-limiting toxicity (DLT) events for 3 weeks after the drug infusion. In this study, DLT will include any of the CTCAE 5.0 grade 3 or higher adverse events (AEs) at least possibly related to the administration of the investigational product, except for an increase in body temperature at least possibly related to the administration of the investigational product, which will be classified as DLT starting from CTCAE 5.0 grade 4.
At the first stage, in the absence of DLT events in three subjects in the same cohort, an ID will be assigned, and an infusion will be administered to the first subject in subsequent cohort. If DLT events occur in 1 of 3 subjects in the same cohort, this cohort will additionally include 3 subjects who will receive the same ANB-004 dose with which the DLT event was observed. If DLT events occur in 2 or more of 3 subjects within the same cohort, the assignment of ID/infusion in subsequent subjects/study is suspended.
AT the second stage, if the IDMC judges that the potentially therapeutic dose was previously used in one of the cohorts, an additional 6 subjects will be included in this cohort.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cohort 1
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.
ANB-004, dose 1
Adeno-associated viral vector carrying the SMN gene single infusion at dose 1. The duration of the infusion is about 60 minutes.
Cohort 2
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.
ANB-004, dose 2
Adeno-associated viral vector carrying the SMN gene single infusion at dose 2. The duration of the infusion is about 60 minutes.
Cohort 3
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.
ANB-004, dose 3
Adeno-associated viral vector carrying the SMN gene single infusion at dose 3. The duration of the infusion is about 60 minutes.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
ANB-004, dose 1
Adeno-associated viral vector carrying the SMN gene single infusion at dose 1. The duration of the infusion is about 60 minutes.
ANB-004, dose 2
Adeno-associated viral vector carrying the SMN gene single infusion at dose 2. The duration of the infusion is about 60 minutes.
ANB-004, dose 3
Adeno-associated viral vector carrying the SMN gene single infusion at dose 3. The duration of the infusion is about 60 minutes.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. 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;
3. A diagnosis of 5q-SMA (homozygous deletion of exon 7 of the SMN1 gene or heterozygous deletion of exon 7 + confirmed point mutation of the SMN1 gene) and 2 or 3 copies of the SMN2 gene established based on molecular genetic testing;
4. Subjects with 2 copies of the SMN2 gene can be included in the study both at the presymptomatic stage of the disease and in the presence of SMA symptoms. If symptoms are present, the age of onset of the disease should be up to 180 days from birth.
5. Subjects with 3 copies of the SMN2 gene can be included in the study if they have symptoms of SMA type 1 and the disease began before the age of 180 days.
6. The ability of the subject's legal representative, in the Investigator's opinion, to perceive information and follow the Protocol procedures
Exclusion Criteria
2. Unwillingness of the legal representative to use alternative feeding methods (nasogastric tube, gastrostomy) in case of swallowing disorders and a risk of aspiration;
3. 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;
4. Need for respiratory support for ≥16 hours per day or tracheostomy ;
5. 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.
6. 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.);
7. 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.
8. 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;
9. A diagnosis of acute or chronic hepatic failure at screening;
10. A known allergy or intolerance to any components of the investigational product or pre- and post-medication drug (glucocorticoids);
11. Simultaneous participation of the subject in other clinical studies or previous participation in another clinical study using an experimental therapy.
240 Days
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Biocad
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Arina V Zinkina-Orikhan, PhD
Role: STUDY_DIRECTOR
Director of Clinical Development Department, BIOCAD
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
1. State Institution Republican Scientific and Practical Center "Mother and Child"
Minsk, , Belarus
Federal State Autonomous Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University", Ministry of Health of the Russian Federation
Moscow, , Russia
Federal State Autonomous Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University", Ministry of Health of the Russian Federation
Moscow, , Russia
Federal State Autonomous Institution "National Medical Research Center for Children's Health", Ministry of Health of the Russian Federation
Moscow, , Russia
Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State Pediatric Medical University", Ministry of Health of the Russian Federation
Saint Petersburg, , Russia
Federal State Budgetary Institution "V. A. Almazov National Medical Research Center" of the Ministry of Health of the Russian Federation
Saint Petersburg, , Russia
State Autonomous Healthcare Institution of the Sverdlovsk Region "Regional Children's Clinical Hospital"
Yekaterinburg, , Russia
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
ANB-004-1
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.