Table 3.
Serious Adverse Events with Direct CNS Administration of AAVrh.10hCLN2 to Cohorts 1 and 41
| Number of Events (% of total events) | ||
|---|---|---|
| Event | Acute/post-operative2 | Chronic3 |
| Any serious adverse event (SAE) | 6 (28.6) | 15 (71.4) |
| Any SAE related to study drug4 | 3 (14.3) | 3 (14.3) |
| Any SAE related to drug administration4 | 6 (28.6) | 7 (33.3) |
| Specific SAE | ||
| Episodes of increased seizures5 | 1 (4.8) | 6 (28.6) |
| Dystonia | 0 (0) | 1 (4.8) |
| Episodes of increased abnormal movements6 | 2 (9.5) | 0 (0) |
| Emesis | 1 (4.8) | 1 (4.8) |
| Hematoma, hemorrhagic contusion | 1 (4.8) | 1 (4.8) |
| Hygroma | 0 (0) | 1 (4.8) |
| Pneumocephalus | 1 (4.8) | 0 (0) |
| Bronchospasm | 0 (0) | 1 (4.8) |
| Aspiration | 0 (0) | 1 (4.8) |
| Pneumonia | 0 (0) | 1 (4.8) |
| Elevated hepatic enzymes | 0 (0) | 2 (9.5)7 |
Serious adverse events (SAE), as defined by 21 CFR 312 (a).
SAEs that occurred from day 0 (day of procedure/vector administration) through day 14 (14 days post-vector administration); reported as number of occurrences (% all occurrences).
SAEs that occurred from month 1 (starting 15 days after the vector administration) through month 18 (540 days post-vector administration); reported as number of occurrences (% all occurrences).
In most cases, in the actual/post-operative period, it is not possible to distinguish as to whether the SAE resulted from the study drug or the drug administration; whenever the SAE was reported as “likely” or “probably” related to the study drug it was listed as “SAE related to study drug”
General tonic-clonic seizures, myoclonic seizures.
Abnormal facial movements, facial twitches/dyskinesia
Transient, mild elevation of ALT, AST at 6 months in S5, cohort 4, resolved without therapy, this subject received the lower dose of 2.85×1011 gc