- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00943579
Open-Label Extension Study of Kuvan for Autism
April 30, 2018 updated by: Glen R. Elliott, The Children's Health Council
Kuvan® (Sapropterin) as a Treatment for Autistic Disorder: An Open Label Extension Protocol
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.
Study Overview
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Palo Alto, California, United States, 94304
- The Children's Health Council
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 years to 6 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- All subjects must have completed earlier trial, CHC 0901 (NCT00850070)
- Parents must be willing and able to sign informed consent
Exclusion Criteria:
- Child failed to complete CHC 0901 (NCT00850070)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Kuvan®
Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks.
|
Brand-name Kuvan® (sapropterin) will be administered to all subjects at a dose of 20 mg/kg/day for 16 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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16 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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).
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Children's Yale Brown Obsessive Compulsive Scale
Time Frame: Weeks 8 & 16
|
The C-YBOCS is a scale is designed to rate the severity of obsessive and compulsive symptoms in children and adolescents, ages 6 to 17 years.
It can be administered by a clinican or trained interviewer in a semi-structured fashion.
In general, the ratings depend on the child's and parent's report; however, the final rating is based on the clinical judgement of the interviewer.
Rate the characteristics of each item over the prior week up until, and including, the time of the interview.
Scores should reflect the average of each item for the entire week, unless otherwise specified.
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Weeks 8 & 16
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Parental Global Assessment
Time Frame: Weeks 8 & 16
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this is a measure of parents impression of improvement.
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Weeks 8 & 16
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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
|
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).
|
Connor's Preschool ADHD Questionnaire
Time Frame: Weeks 8 & 16
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This is a measure of behavioral symptomatology in children 2-6 years of age.
The ADHD scale is one subdomain.
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Weeks 8 & 16
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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
|
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).
|
Adverse Events Reporting
Time Frame: Cummulative throughout study
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This is not a standardized measure but instead a set of questions, both closed and open ended, asked of families about their child's response to the medication.
Used for determining whether treatment needed to be discontinued.
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Cummulative throughout study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Glen R Elliott, PhD, MD, The Children's Health Council
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2009
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
March 1, 2012
Study Registration Dates
First Submitted
July 20, 2009
First Submitted That Met QC Criteria
July 20, 2009
First Posted (Estimate)
July 22, 2009
Study Record Updates
Last Update Posted (Actual)
May 2, 2018
Last Update Submitted That Met QC Criteria
April 30, 2018
Last Verified
April 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHC-0902
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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