Objective: To evaluate the efficacy and safety of deutetrabenazine (DTBZ) in children and adolescents with dyskinesia in cerebral palsy (DCP).

Background: There are currently no approved treatments for DCP, which affects 6%–15% of patients with cerebral palsy. DTBZ is a vesicular monoamine transporter type 2 inhibitor that is FDA approved for the treatment of Huntington disease-associated chorea and tardive dyskinesia in adults. This phase 3 study assessed DTBZ efficacy and safety in DCP for the first time.

Method: In RECLAIM-DCP (NCT03813238), patients aged 6–‍18 years diagnosed with DCP, with non-progressive symptoms since infancy, were randomized 2:1 to receive daily oral DTBZ or placebo for 15 weeks (dosed by weight and CYP2D6 impairment). The primary efficacy endpoint was change in Movement Disorder-Childhood Rating Scale part II total score (MD-CRS II; centrally read) from baseline (BL) to week 15. Key secondary outcomes included MD-CRS I, Unified Huntington’s Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC), UHDRS-Total Maximal Dystonia (all centrally read), Caregiver Global Impression-Improvement (GI-I), and Clinical GI-I, as well as safety.

Results: Because of persistent recruitment challenges, the sample size was amended. Of 63 patients randomized (41 DTBZ, 22 placebo), 52 (83%) completed treatment. Patient characteristics were similar between groups (mean age, 11.3 vs 11.5 years; 98% vs 95% White; 71% vs 55% male; mean BL MD-CRS II, 11.7 vs 10.4). Despite numerical improvements at weeks 9, 12, and 15, the mean difference in MD-CRS II change from BL to week 15 was not statistically significant (least-squares mean difference vs placebo, −‍1.2 [95% CI, −‍3.49 to 1.19]; P=.34), likely because of the small sample size. Among the secondary efficacy endpoints, the change in UHDRS-TMC from BL to week 15 was statistically significant (−‍1.4 [−‍2.81 to −‍0.04]; nominal P=.04). Adverse events (AEs) were reported for 35 (88%) and 15 (68%) patients in the DTBZ and placebo groups, respectively, and were in line with the established safety profile of DTBZ. There were no deaths or serious AEs; 2 patients (both DTBZ) had severe AEs.

Conclusion: This underpowered trial did not meet its primary efficacy endpoint. However, some improvement in the chorea component of DCP, favoring DTBZ, was observed. This study identified no new safety signals beyond the established safety profile of DTBZ.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-deutetrabenazine-in-children-and-adolescents-with-dyskinesia-in-cerebral-palsy/