| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10041582 | | E.1.2 | Term | Spinal muscular atrophy | | E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders | |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | 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®).
| |
| E.2.2 | Secondary objectives of the trial | | 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®). | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | ● 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. | |
| E.4 | Principal exclusion criteria | ● 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 | |
| E.5 End points |
| E.5.1 | 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. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | Secondary end point(s) | The secondary endpoints for the secondary objective questions of interest are:
● What is the change from baseline to Week 52 visit in the Hammersmith Functional Motor Scale Expanded (HFMSE) total score?
● What is the change from baseline to Week 52 visit in the Revised Upper Limb Module (RULM) total score?
● What is the change from baseline to Week 52 visit in Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument score? | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Australia | | Canada | | Japan | | United States | | Belgium | | France | | Germany | | Italy | | Netherlands | | Spain | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | Study completion is defined as when the last participant finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 10 |
