Clinical Trial: Open-Label Extension Study of Kuvan for Autism

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Kuvan® (Sapropterin) as a Treatment for Autistic Disorder: An Open Label Extension Protocol

Brief Summary: This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. During this protocol, all subjects will be receiving brand-name Kuvan 20 mg/kg/day for 16 weeks; subject who complete the first 16 weeks will have the option of continuing on Kuvan at the same dose for up to 90 days after the last subject has completed the first 16 weeks of this protocol. The purpose of the study primarily is to gather additional information on safety and efficacy in this population.

Detailed Summary: This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. During this protocol, all subjects will be receiving brand-name Kuvan 20 mg/kg/day for 16 weeks; subject who complete the first 16 weeks will have the option of continuing on Kuvan at the same dose for up to 90 days after the last subject has completed the first 16 weeks of this protocol. The purpose of the study primarily is to gather additional information on safety and efficacy in this population.
Sponsor: The Children's Health Council

Current Primary Outcome: Clinical Global Impressions Scale [ Time Frame: 16 weeks ]

This is a summary judgment made by a trained clinician based on observed and reported behaviors of the child compared to baseline. It is a 7-point scale (1) very much improved, (2) much improved, (3) minimally improved (4) no change, (5) minimally worse, (6) much worse and (7) very much worse. Chi-square analyses were used to assess change in CHI-I scores (by group, post-test)Mixed-effects regression models determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. The mixed-effects regression model is robust to data dependency that occurs with the repeated assessments of individuals over time & can handle missing data. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time


Original Primary Outcome: Clinical Global Impressions Scale [ Time Frame: 16 weeks ]

Current Secondary Outcome:

  • Vineland Adaptive Behavior Scale, 2nd Edition [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ]
    The Vineland-2 is semi-structured interview designed to communication, daily living, socialization and motor skills. The Vineland-2 is comprised of a total Adaptive Composite Scale; we chose to use 10 subscales that specifically address functional domains relevant for a young ASD sample - Receptive Communication, Expressive Communication, Personal Daily Living Skills, Domestic Daily Living Skills, Community Daily Living Skills, Interpersonal Relations, Play Skills, Coping Skills, Gross Motor Skills, Fine Motor Skills. The scales generate raw or sum, V-, and age-equivalent scores; raw scores were selected for use in this study. Higher subscale scores indicate more skills. Raw scores can range from 0 to 766 for the overall adaptive behavior composite. Subscales are combined to form the overall Adaptive Behavior Composite, which is essentially a weighted average of the various subscales combined.
  • Children's Yale Brown Obsessive Compulsive Scale [ Time Frame: Weeks 8 & 16 ]
  • Parental Global Assessment [ Time Frame: Weeks 8 & 16 ]
  • Preschool Language Scale, 4th Edition (PLS-4) [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ]
    Measures expressive & receptive language and total scores in ages 0 to 6 years 11 months. The scales generate raw, standard, and age-equivalent scores; raw scores for the total scale were selected for use in this study. Total is average of subscales. Minimum raw score = 0, maximum = 130. Higher raw scores indicate better language skills. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept & trend modeling that accounts for each individual's initial level of symptom severity/functioning & rate of change/time
  • Connor's Preschool ADHD Questionnaire [ Time Frame: Weeks 8 & 16 ]
  • Aberrant Behavior Checklist (ABC) [ Time Frame: Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). ]
    This is a 58-item informant-based, factor-analyzed scale comprised of a total scale and 5 subscales that generate raw scores. Scores based on a likert scale ranging from 0-3 where 0 is not a problem to 3 where the problem is severe. Subscales include: Irritability, Social Withdrawal, Stereotypic Behaviors, Hyperactivity and Inappropriate Speech. Total maximum score is 174. Higher subscale scores indicate more symptoms. Scores are totaled to compute subscale scores. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time
  • Adverse Events Reporting [ Time Frame: Cummulative throughout study ]


Original Secondary Outcome:

  • Vineland Adaptive Behavior Scale [ Time Frame: Weeks 8 and 16 ]
  • Clinical Global Impression: Severity [ Time Frame: Weeks 8 & 16 ]
  • Children's Yale Brown Obsessive Compulsive Scale [ Time Frame: Weeks 8 & 16 ]
  • Parental Global Assessment [ Time Frame: Weeks 8 & 16 ]
  • Preschool Language Scale [ Time Frame: Weeks 8 & 16 ]
  • Connor's Preschool ADHD Questionnaire [ Time Frame: Weeks 8 & 16 ]
  • Aberrant Behavior Checklist [ Time Frame: Weeks 8 & !6 ]
  • Adverse Events Reporting [ Time Frame: Cummulative throughout study ]


Information By: The Children's Health Council

Dates:
Date Received: July 20, 2009
Date Started: August 2009
Date Completion:
Last Updated: July 2, 2013
Last Verified: July 2013