Spinal Muscular Atrophy MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Zolgensma
Product Name: OAV101
Product Code: OAV101
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ONASEMNOGENE ABEPARVOVEC
CAS Number: 1922968-73-7
Current Sponsor code:
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnostic confirmation during screening period 5q SMA - The patient must be treatment naive (historical or current use) for all SMN-targeting therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)). - =2 years and 2 years from screening in the opinion of the Investigator - Meets age-appropriate institutional criteria for use of anesthesia/sedation as assessed by the physician responsible for administering anesthesia/sedation (Full list of inclusion criteria can be found in the clinical protocol Section 5.1) Are the trial subjects under 18? yes Number of subjects for this age range: 125 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Excluding SMA, any medical condition considered clinically significant by the Investigator, including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder including diabetes mellitus, gastrointestinal disorders, metabolic disorders, untreated B6 deficiency, severe respiratory compromise and significant brain abnormalities at either Screening or Baseline that, in the opinion of the investigator, would interfere with the overall interpretation of safety or efficacy of the study. - Anti-AAV9 antibody titer reported as elevated (reference to >1:50 or validated results consistent with being elevated) at Screening as determined by ligand binding immunoassay. - Clinically significant abnormalities in test results during screening period and/or during baseline period as determined by the Investigator - Participants will be excluded from the trial for inpatient surgery hospitalization, hospitalization for a pulmonary event, or hospitalization for nutritional support within 2 months prior to Screening and up to Day 1. In addition, patients will not be eligible for the trial if at Screening, inpatient major surgery is planned at any time during the 64-week study. Any other surgeries must not interfere with the ability of the patient to perform the study assessments. - Prior injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the participant's ability to perform any of the outcome measure testing required in the protocol and from which the participant has not fully recovered or achieved a stable baseline upon entry into screening period - Contraindications for lumbar puncture procedure, (including but not limited to cutaneous infection at the treatment site and signs or symptoms of increased intracranial pressure), active administration of any intrathecal therapy, presence of an implanted shunt for the drainage of CSF, presence of an implanted central nervous system (CNS) catheter, or any impediment to CSF access. (Full list of exclusion criteria can be found in the clinical protocol Section 5.2)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of OAV101 IT vs. sham control as measured by the change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) total score. ;Secondary Objective: - To compare the efficacy of OAV101 IT vs. sham control in two patient age groups: = 2 to < 5 years (HFMSE, Revised Upper Limb Module (RULM)); = 2 to < 18 years (RULM) - To evaluate the safety and tolerability of OAV101 IT vs. sham control in patients = 2 to < 18 years) ;Primary end point(s): Change from baseline in HFMSE total score at the end of Follow-up Period 1 (defined in Section 12.4.1 of the clinical protocol) in the overall study population (= 2 to < 18 years age group) ;Timepoint(s) of evaluation of this end point: up to 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in HFMSE total score at the end of Follow-up Period 1 in the = 2 to < 5 years age group - Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the overall study population - Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the = 2 to < 5 years age group - Change from baseline in RULM at the end of Follow-up Period 1 in the =2 to < 18 years age group - Change from baseline in the RULM at the end of Follow-up Period 1 in the = 2 to < 5 years age group - Incidence of treatment emergent adverse events (TEAEs) and serious TEAEs (SAEs) - Number of participants with adverse events of special interest (AESIs) - Evaluation of changes from baseline in vital signs, physical/neurological examinations, laboratories (chemistry, hematology, liver function tests), echocardiogram, ECG, anthropometry, and C-SSRS - Number (and percentage) of patients with intracardiac thrombi - Number (and percentage) of patients with low cardiac function ;Timepoint(s) of evaluation of this end point: Up to 12 months | — |
Countries
Brazil, China, Colombia, Denmark, Egypt, Greece, India, Italy, Malaysia, Mexico, Russian Federation, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, United Arab Emirates, United States, Viet Nam
Contacts
Public ContactMedical Information
Novartis Healthcare A/S
Outcome results
None listed