SURAMIN INTRAVENOUS INFUSION FOR TREATING BOYS WITH AUTISM SPECTRUM DISORDER: RESULTS OF A 14-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIDOSE, PHASE 2 STUDY

Abstract

Objectives: The objective of this presentation is to test the efficacy and safety of 2 doses of suramin vs placebo in children aged 4 to 17 years with autism spectrum disorder (ASD). The hypotheses are that at least 1 of 2 suramin doses would show improvement in the Aberrant Behavior Checklist (ABC) Core score and that treatment would be safe and tolerable. Methods: Fifty-two boys were enrolled in 3 treatment arms: 10 mg/kg and 20 mg/kg, and placebo dosed at baseline, at weeks 4 and 8. Subjects were diagnosed by DSM-5 criteria and severity measured by the Autism Diagnostic Observation Schedule. The main efficacy analyses were ABC Core (subscales 2, 3, and 5) and Clinical Global Impression–Improvement (CGI-I) scale. Question 1 was assessed using intent-to-treat sample change scores from baseline to endpoint using ANOVA. Although the study was not designed for formal statistical comparison, ABC Core and CGI-I were tested at a family-wise Type I level of 0.05 using Dunnett’s p value for multiple comparisons. The study was approved by the South Africa Health Products Regulatory Authority and each site’s IRB. Results: The study was conducted at 6 sites in South Africa. The sample was multiracial with a mean age of approximately 8 years and a range of 4 to 15 years. There was a wide variability in the severity of ASD symptoms at baseline. Forty-four subjects completed the study, and there were 8 early withdrawals (COVID-19: 5;serious adverse event [SAE]: 1;other reason: 2). The 10 mg arm showed a sustained benefit across time points. The ABC Core modeling mean ± standard error (SE) of 10 mg showed a greater numeric improvement (–12.5 ± 3.18) vs placebo (–8.9 ± 2.86) (nonsignificant) at Week 14. The 20 mg arm did not show improvement vs placebo at Week 14. In exploratory analyses, the 10 mg arm showed greater differences from placebo in ABC Core in younger and less severe subjects. CGI-I modeled mean ± SE changes from baseline were 2.8 ± 0.30 (p = 0.016) in the 10 mg arm and 2.0 ± 0.28 (p = 0.65) in the 20 mg arm vs 1.7 ± 0.27 in the placebo. Suramin was generally safe and well tolerated over 14 weeks. There was 1 SAE, status epilepticus, in a subject (20-mg arm) with multiple risk factors for seizure;it resolved without sequelae. Conclusions: This dose-ranging proof-of-concept study showed some positive results from a treatment with a novel mechanism of action. Limitations include the small sample size and exploratory analyses that require confirmation in a larger study. Suramin was safe and tolerable over 14 weeks.