Phase IIIb, open-label, multi-center study to evaluate safety, tolerability and efficacy study of OAV101 administered intrathecally to participants with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen or risdiplam
- Conditions
- Spinal Muscular AtrophyMedDRA version: 20.1Level: PTClassification code 10041582Term: Spinal muscular atrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2021-006709-31-DE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 28
? Written informed consent
? SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations and any copy of SMN2 gene
? Aged 2 to <18 years (screening visit must occur before the patient's 18th birthday) at time of Screening Visit 1
? Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
? Must be able to sit independently but must never have taken steps independently
? Diagnosed through newborn or neonatal screening or patients clinically diagnosed must have age of clinical symptom onset < 18 months
? Meets age-appropriate institutional criteria for use of anesthesia/sedation
? Female participants who are sexually active or have reached menarche must have a negative pregnancy test at Screening. Those females who are sexually active must also agree to use highly effective methods of contraception.
Are the trial subjects under 18? yes
Number of subjects for this age range: 28
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
? Excluding SMA, any medical condition considered clinically significant
? Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis
? Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated at Screening (reference to >1:50 or a validated result consistent with being elevated)
? Clinically significant abnormalities in test results during screening period and/or at Baseline
? Platelet count less than the lower limit of normal (LLN), or platelet transfusion within 1 month at Screening Visit 1
? Clinically significant abnormal coagulation panel results at Screening
? Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin (TBL), gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) > upper limit of normal (ULN) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated elevated AST is not considered exclusionary)
? Contraindications for lumbar puncture procedure
? At Baseline (Day-1), participants are excluded if they received:
?nusinersen (Spinraza®) within 4 months at Baseline
? risdiplam (Evrysdi®) within 15 days at Baseline
? Vaccinations 2 weeks prior to administration of OAV101
? Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
? Presence of the following:
? An active infectious process requiring systemic antiviral or antimicrobial therapy up to 30 days prior to OAV101 administration, or
? An active but untreated viral or bacterial infectious process up to 30 days prior to administration of OAV101, or
? Any febrile illness up to 30 days prior to administration of OAV101
? Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours during a 24-hour period, noninvasive ventilation for >12 hours during a 24-hour period or requiring tracheostomy, at Screening and up to OAV101 administration
? Concomitant use of any of the following medication categories within 90 days prior to administration of OAV101
? Ongoing systemic immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab), plasmapheresis, immunomodulators (e.g., adalimumab)
? History of hypersensitivity to any of the study treatments or its excipients or drugs of similar chemical classes
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to characterize the safety and tolerability of OAV101 intrathecal (IT) over a 52-week period in patients with SMA aged 2 to < 18 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).<br>;Secondary Objective: The secondary objective of this study is to assess the efficacy of OAV101 IT on motor function and caregiver impact over a 52-week period in patients with SMA aged 2 to < 18 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).;Primary end point(s): The primary endpoints for the primary objectives are: the number and percentage of participants reporting adverse events (AEs), related AEs, serious AEs and adverse events of special interest (AESIs) over a 52-week period.;Timepoint(s) of evaluation of this end point: 52 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary endpoints for the secondary objective questions of interest are: <br>? What is the change from baseline to Week 52 visit in the Hammersmith Functional Motor Scale Expanded (HFMSE) total score?<br>? What is the change from baseline to Week 52 visit in the Revised Upper Limb Module (RULM) total score?<br>? What is the change from baseline to Week 52 visit in Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument score?;Timepoint(s) of evaluation of this end point: 52 weeks