Abstracts

Rationale: Evaluate cognitive and behavioral effects and tolerability of long-term adjunctive brivaracetam (BRV) in children and adolescents with focal seizures.

Methods: Interim post-hoc analysis (cutoff 14Jul2020) of pooled data from a Phase IIa, open-label trial (N01263/NCT00422422; 0.8–4 mg/kg/day BRV oral solution; ≥ 1 month to < 16 years) and an ongoing, Phase III, open-label, long-term follow-up trial of N01263 (N01266/NCT01364597; max 5 mg/kg/day BRV tablet or oral solution, not to exceed 200 mg/day; patients directly enrolling aged ≥ 4 to < 17 years). Cognitive and behavioral outcomes were assessed with Achenbach CBCL (patients aged 1.5–5 and 6–16 years) and BRIEF-P/BRIEF (patients aged < 5 and 5–16 years, respectively).

Results: 140 patients were analyzed (mean age: 9.5 years; 57.1% male; 32 [22.9%] aged 1.5–5 years, 108 [77.1%] aged 6–16 years; median exposure: 3.6 and 3.5 years, respectively; Safety Set). Mean change from Baseline to final visit in raw subscale scores were (i) Achenbach CBCL 1.5–5 aggressive behavior, anxious/depressed, attention problems, emotionally reactive, sleep problems, somatic complaints, withdrawn, other problems: -1.4, -1.5, -0.5, -1.0, -1.1, -0.9, -0.7, -3.2, respectively; (ii) Achenbach CBCL 6–18 aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, social problems, somatic complaints, thought problems, withdrawn/depressed: -1.8, -1.4, -1.2, -0.7, -0.5, -1.2, -0.8, -0.1; (iii) BRIEF-P inhibit, shift, emotional control, working memory, plan/organize: -6.6, -2.1, -4.9, -4.0, -3.0; (iv) BRIEF inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials, monitor: -1.6, -0.5, -1.0, -0.6, -1.8, -1.4, -0.8, -0.9. In both age groups, the vast majority of patients had no shift in T-score category from Baseline to last evaluation for each Achenbach CBCL subscale (between normal and borderline or clinical range [BCR], Fig. 1) and BRIEF-P/BRIEF subscale (between normal and potential clinical significance [PCS], Fig. 2). For all Achenbach CBCL subscales, the proportion of patients aged 1.5–5 and 6–18 years, respectively, who changed from BCR to normal (range 6.2–21.9%, 12.7–18.6%) was higher than those who changed from normal to BCR (range 3.1–9.4%, 2.9–13.7%). Changes that occurred across the BRIEF-P subscales were mostly from PCS to normal (range 14.3–28.6%). Across the BRIEF subscales, similar proportions of patients changed from normal to PCS (range 6.9–16.8%), or from PCS to normal (range 6.9–12.9%). Treatment-emergent adverse events (TEAEs) were reported in patients aged 1.5–5 and 6–16 years, respectively: overall (100%, 95.4%); drug-related TEAEs (40.6%, 34.3%); serious TEAEs (18.8%, 26.9%); discontinuations due to TEAEs (6.3%, 7.4%); deaths (3.1% [n=1], 0.9% [n=1]).

Conclusions: In this pooled, interim analysis, cognitive and behavioral functioning scores in children and adolescents with focal seizures under long-term adjunctive BRV therapy were generally stable or slightly improved. BRV was generally well tolerated.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.