Folinic Acid as a Treatment for Autism Spectrum Disorder in Children

Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)

Change from baseline to Week 12 in standardized language function scores as assessed using the Clinical Evaluation of Language Fundamentals (CELF), a standardized individually administered assessment of receptive and expressive language skills in children. CELF standardized scores have a mean of 100 and a standard deviation of 15, with higher scores indicating better language performance. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)

Change from baseline to Week 12 in standardized receptive vocabulary scores as assessed using the Receptive One-Word Picture Vocabulary Test (ROWPVT), a standardized individually administered assessment of a child's ability to understand spoken words. Scores are standardized with a mean of 100 and a standard deviation of 15, where higher scores indicate better receptive vocabulary ability. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)

Change from baseline to Week 12 in standardized expressive vocabulary scores as assessed using the Expressive One-Word Picture Vocabulary Test (EOWPVT), a standardized individually administered assessment of a child's ability to produce spoken words. Scores are standardized with a mean of 100 and a standard deviation of 15, where higher scores indicate better expressive vocabulary ability. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in Clinical Global Impression-Severity and Improvement scores as measured by the Clinical Global Impression Scale (CGI-S and CGI-I)

Change from baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores, assessed using the Clinical Global Impression Scale, a standardized assessor-rated measure of illness severity and overall clinical improvement. CGI-S scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill), where lower scores indicate better outcomes, and CGI-I scores range from 1 (very much improved) to 7 (very much worse), where lower scores indicate greater improvement. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)

Change from baseline to Week 12 in total scores on the Aberrant Behavior Checklist (ABC), a standardized caregiver-completed questionnaire that assesses behavioural symptoms in children across domains such as irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech. Total scores range from 0 to 174, with higher scores indicating greater severity of behavioural problems (worse outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL)

Change from baseline to Week 12 in total problem scores on the Child Behavior Checklist (CBCL), a standardized caregiver-reported questionnaire that assesses a broad range of emotional and behavioural problems in children. Total scores are standardised T-scores (typically ranging from approximately 30 to 100, with a mean of 50 and standard deviation of 10), where higher scores indicate greater behavioural and emotional problems (worse outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS)

Change from baseline to Week 12 in standardised adaptive behavior scores as assessed using the Vineland Adaptive Behavior Scales (VABS), a standardized caregiver-reported assessment of a child's adaptive functioning across domains such as communication, daily living skills, socialization, and motor skills. Adaptive behavior composite scores are standardised (typically ranging from approximately 20 to 160, with a mean of 100 and standard deviation of 15), where higher scores indicate better adaptive functioning (better outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment

Change from baseline to Week 12 in eye-tracking measures of visual attention, specifically the proportion of total gaze duration directed toward social stimuli (e.g., faces or biological motion) compared with non-social stimuli, assessed using a standardized eye-tracking paradigm. Higher proportions indicate greater relative attention to social stimuli. Changes in proportions will be compared between participants receiving folinic acid and those receiving placebo.

Time frame: Baseline to Week 12

Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid

Change from baseline to Week 24 in the incidence of adverse events (AEs) and serious adverse events (SAEs), monitored throughout the study period to assess the safety and tolerability of folinic acid treatment.

Time frame: Baseline to Week 24