A Phase 2/3 interventional study of Kuvan® in Autistic Disorder, sponsored by The Children's Health Council. Completed at 1 site in United States. Open to participants aged 3 Years to 6 Years. Per ClinicalTrials.gov, last updated 2018-05-02.
Sponsored by The Children's Health Council · Phase 2/3, Interventional, and Treatment
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.
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.
1,360 studies on the registry are indexed under Autistic Disorder; 332 are open to participants now.
This study's enrollment of 41 is below the median of 46 across 1,058 interventional studies indexed under Autistic Disorder.
Browse Autistic Disorder studies →The Children's Health Council is the lead sponsor of 2 studies on the registry; none are open to participants now.
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Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks.
Drug: Kuvan®
Brand-name Kuvan® (sapropterin) will be administered to all subjects at a dose of 20 mg/kg/day for 16 weeks.
Also known as: sapropterin, tetrahydrobiopterin
Clinical Global Impressions Scale
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
Time frame: 16 weeks
Vineland Adaptive Behavior Scale, 2nd Edition
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.
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).
Children's Yale Brown Obsessive Compulsive Scale
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.
Time frame: Weeks 8 & 16
Parental Global Assessment
this is a measure of parents impression of improvement.
Time frame: Weeks 8 & 16
Preschool Language Scale, 4th Edition (PLS-4)
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
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).
Connor's Preschool ADHD Questionnaire
This is a measure of behavioral symptomatology in children 2-6 years of age. The ADHD scale is one subdomain.
Time frame: Weeks 8 & 16
Aberrant Behavior Checklist (ABC)
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
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).
Adverse Events Reporting
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.
Time frame: Cummulative throughout study
Recruitment spanned from 08/09 - 10/11. Only individuals who completed 0901 (NCT00850070) were eligible to participate in this study thus recruitment was restricted to those already enrolled in that trial. When participants were at their 12-week visit for 0901 (NCT00850070) they were asked if they wanted to continue in the open label extension.
| Milestone | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Started | 21 | 20 |
| Completed | 15 | 15 |
| Not completed | 6 | 5 |
| Withdrew: Adverse event | 4 | 3 |
| Withdrew: Lack of efficacy | 2 | 2 |
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
| # participants much - very much improved | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Clinical Global Impressions Scale | 3 | 3 |
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.
| units on a scale | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Vineland Adaptive Behavior Scale, 2nd Edition | 275 ± 10.77 | 321 ± 10.78 |
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.
No measurements were reported for this outcome.
this is a measure of parents impression of improvement.
No measurements were reported for this outcome.
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
| units on a scale | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Preschool Language Scale, 4th Edition (PLS-4) | 57.24 ± 5.48 | 77.83 ± 5.27 |
This is a measure of behavioral symptomatology in children 2-6 years of age. The ADHD scale is one subdomain.
No measurements were reported for this outcome.
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
| units on a scale | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Aberrant Behavior Checklist (ABC) | 16.84 ± 1.68 | 9.70 ± 1.73 |
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.
No measurements were reported for this outcome.
Collected over Adverse events were monitored for the length of the study, i.e., 16 weeks.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Kuvan Following Placebo | — | 0/21 (0%) | 14/21 (66.7%) |
| Kuvan Following Active Treatment | — | 0/20 (0%) | 13/20 (65%) |
| Event | Kuvan Following Placebo | Kuvan Following Active Treatment |
|---|---|---|
| Difficulty SleepingNervous system disorders | 6/21 | 5/20 |
| Changes in bowel movementsGastrointestinal disorders | 5/21 | 5/20 |
| Repetitive BehaviorsNervous system disorders | 3/21 | 5/20 |
| IrritabilityPsychiatric disorders | 3/21 | 4/20 |
| HyperactivityNervous system disorders | 3/21 | 0/20 |
| AnxietyPsychiatric disorders | 2/21 | 0/20 |
| RashSkin and subcutaneous tissue disorders | 1/21 | 0/20 |
| Age, Categorical(Participants) | Kuvan Following Placebo | Kuvan Following Active Treatment | Total |
|---|---|---|---|
| <=18 years | 21 | 20 | 41 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Kuvan Following Placebo | Kuvan Following Active Treatment | Total |
|---|---|---|---|
| Mean | 5 ± 1 | 5 ± 1 | 5 ± 1 |
| Sex: Female, Male(Participants) | Kuvan Following Placebo | Kuvan Following Active Treatment | Total |
|---|---|---|---|
| Female | 5 | 5 | 10 |
| Male | 16 | 15 | 31 |
| Region of Enrollment(participants) | Kuvan Following Placebo | Kuvan Following Active Treatment | Total |
|---|---|---|---|
| United States | 21 | 20 | 41 |
This study is completed, as verified in Apr 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sapropterin
The Children's Health Council