Double Blind Trial in Children With Autism Spectrum Disorder

A Three-Arm, Prospective, Randomized, Double Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of 2 Doses of Suramin vs. Placebo in Male Children With ASD Receiving Standard Treatment

This study investigated the safe and efficacious use of suramin as a novel treatment for ASD by testing two suramin doses vs placebo

PUR-ONQ-ASD-001 was a multicenter, 3-arm, prospective, randomized, double blind, placebo-controlled multiple dose trial involving 2 dose levels of suramin vs. placebo. The study randomized 52 male participants who received treatment interventions for ASD; each treatment arm was assigned approximately 17 participants. The number of participants was increased to 52 participants (48 originally planned) due to early withdrawals related to the COVID-19 global pandemic lockdowns and other matters. Participants were stratified by age, ADOS-2, and Non-verbal Intelligence Quotient (NVIQ). Participants who met all the inclusion criteria and none of the exclusion criteria were randomized through an electronic system to either arm A (10 mg/kg suramin) or Arm B (20 mg/kg suramin) or Arm C (Placebo) in a targeted 1:1:1 ratio, as per the randomization schedule and stratified by age, ADOS-2, and NVIQ. All participants received a 50 mg test dose at their first administration (0.5 mL of freshly reconstituted 10% solution in 5 mL saline) to check for allergic reactions. The test dose was given by slow intravenous (IV) infusion for 30 minutes then flushed with 10 mL saline. Vitals were checked for 30 min and if there were no changes or evidence of allergic reaction, the rest of the study drug dose was administered (10 mg/kg or 20 mg/kg minus test dose [minus 50 mg] in a 50 mL saline up to a maximum of 1 g given over 30 minutes). Arm A - 50 mg test dose of suramin (upon first administration), then suramin 10 mg/kg (minus 50 mg suramin test dose) in 50 mL of saline administered by IV infusion over 30 minutes was given at Visits 2, 4 and 5. The maximum dose administered was 1 g. Arm B - 50 mg test dose of suramin (upon first administration), then suramin 20 mg/kg (minus 50 mg suramin test dose) in 50 mL of saline administered by IV infusion over 30 minutes was given at Visits 2, 4 and 5. The maximum dose administered was 1 g. Arm C - Test dose of saline placebo, then saline placebo IV infusion of 50 mL administered over 30 minutes was given at Visits 2, 4 and 5

The participants were randomized to one of three double-blind treatment groups, i.e., Arm A (10 mg/kg suramin) or Arm B (20 mg/kg suramin) or Arm C (placebo) in a targeted 1:1:1 ratio, as per the randomization schedule and stratification plan. The stratification plan was to match patients by age (< 7 vs ≥ 7), ADOS-2 comparison scores (≤ 8.5 vs > 8.5) and NVIQ (≤ 80 vs > 80)

The study was double-blind. Suramin and placebo are both clear solutions when prepared. Suramin was prepared by an unblinded pharmacist by reconstituting 1 g vial of suramin in 10 mL of sterile water for infusion to prepare a 10% (100 mg/mL) solution.

50 mg test dose of suramin (upon first administration), then suramin 10 mg/kg (minus 50 mg suramin test dose) in 50 mL of saline administered by IV infusion over 30 minutes was given at Visits 2, 4, and 5.

50 mg test dose of suramin (upon first administration), then suramin 20 mg/kg (minus 50 mg suramin test dose) in 50 mL of saline administered by IV infusion over 30 minutes was given at Visits 2, 4, and 5.

Test dose of saline placebo, then saline placebo infusion of 50 mL administered over 30 minutes was given at Visits 2, 4, and 5.

The primary objective was to evaluate the safety and efficacy of 2 dose levels of low dose suramin against placebo in children with ASD receiving standard treatment.

Inclusion Criteria: Male children aged 4 - 17 years Participants with or without treatment interventions for ASD Participants must have been diagnosed with ASD by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) Autism diagnostic observation schedule, version 2 (ADOS-2) Comparison scores in the moderate and high level as evaluated on the ADOS-2 Stable treatment intervention for ≥ 2 months Participants agreed to not change their treatment interventions throughout the study duration Participants on Ritalin and Risperdal or similar medication agreed to not change their dose during the study Exclusion Criteria: Hospitalization within the previous 2 months An acute medical problem, Rett syndrome, microcephaly, tuberous sclerosis, neurofibromatosis, epilepsy, or clinically significant liver, kidney, or adrenal disease or persons suffering from any serious acute condition where, in the investigator's opinion, the participant's well-being may have been compromised Planning to start a new drug, diet, or behavioral intervention during the study Weight under the 5th percentile for age Unable to tolerate venipuncture, urine collection, or an indwelling IV catheter for 3-4 hours Plasma creatinine above normal for age and weight according to the laboratory reference ranges. Liver function alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5-fold above the upper limit of normal Known intolerance to suramin or other antipurinergic drugs Unable to perform or cooperate with study requirements Children with known syndromic forms of ASD caused by DNA mutation or chromosomal copy number variation