| 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 | | 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. | |
| E.2.2 | Secondary objectives of the trial | - 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)
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 <18 years of age at screening visit 1
- Onset of clinical signs and symptoms at ≥ 6 months of age
- Patient must have a complete HFMSE assessment with available total score as administered by qualified clinical evaluator during the screening period for trial eligibility
- Able to sit independently at screening, but has never had the ability to walk independently.
- Estimated life expectancy > 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) | |
| E.4 | Principal 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) | |
| E.5 End points |
| E.5.1 | 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)
| |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | 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
| |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 2 |
| 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 | | Colombia | | Egypt | | Malaysia | | Singapore | | United Arab Emirates | | Taiwan | | Brazil | | China | | India | | Mexico | | Russian Federation | | Saudi Arabia | | South Africa | | Thailand | | United States | | Viet Nam | | Denmark | | Greece | | Italy | |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 2 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| 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 | 5 |
