AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial

Abstract

Aim: This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children.

Methods: This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12.

Results: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea.

Conclusions: Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD.

Keywords: autism; children; clinical trial; social communication.

Fig. 1

Consolidated Standards of Reporting Trials (CONSORT) flow diagram for this clinical trial.

Fig. 2

Mean Korean Vineland Adaptive Behavior Scales, 2nd Edition (K‐VABS‐II) Adaptive Behavior Composite (ABC) (a) and Clinical Global Impression‐Severity (CGI‐S) (b) scores over 36 weeks.

Fig. 3

Treatment differences in Korean Vineland Adaptive Behavior Scales, 2nd Edition (K‐VABS‐II) domain and Korean‐Parenting Stress Index‐4th Edition‐Short Form (K‐PSI‐4‐SF) Parental Distress subscale scores at 12 weeks. cFB, confidence level for bounds; CI, confidence interval; LSM, least‐squares mean; SE, standard error.