Trial Outcomes & Findings for Study of Kuvan Treatment in Adults With GTPCH Deficiency (NCT NCT01425528)
NCT ID: NCT01425528
Last Updated: 2025-04-01
Results Overview
Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Baseline, 8 wks, 12 wks
Results posted on
2025-04-01
Participant Flow
Participants were recruited from August 2011 through August 2013. Participants were patients who had been seen clinically for GTPCH deficiency and indicated previously that they would be interested in future research.
This is a pilot study and all participants are in the treatment group.
Participant milestones
| Measure |
Cohort 1
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
|
Cohort 2
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Cohort 1
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
|
Cohort 2
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Study of Kuvan Treatment in Adults With GTPCH Deficiency
Baseline characteristics by cohort
| Measure |
Cohort 1
n=6 Participants
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
Cohort 2
n=6 Participants
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42 years
n=99 Participants
|
28 years
n=107 Participants
|
35 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=99 Participants
|
6 participants
n=107 Participants
|
12 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, 8 wks, 12 wksPopulation: Data from 4 of 6 participants was analyzed for Kuvan Cohort 1 and for Kuvan Cohort 2 for this outcome measure. 2 participant withdrew, 1 participant's diagnosis was reclassified and we were unable to obtain baseline CSF on 1 participant.
Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
Cohort 2
n=4 Participants
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
|---|---|---|
|
Change in BH4 Levels in Cerebral Spinal Fluid
Change in BH4 from Baseline at 8 weeks
|
6 nmol/L
Standard Deviation 1.4
|
10.7 nmol/L
Standard Deviation 4.8
|
|
Change in BH4 Levels in Cerebral Spinal Fluid
Change in BH4 from Baseline at 12 weeks
|
5.3 nmol/L
Standard Deviation 3.8
|
13.2 nmol/L
Standard Deviation 3.9
|
Adverse Events
Cohort 1
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1
n=6 participants at risk
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
Cohort 2
n=6 participants at risk
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
|---|---|---|
|
Psychiatric disorders
Uncontrollable Anger
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
0.00%
0/6 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
Other adverse events
| Measure |
Cohort 1
n=6 participants at risk
This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
Cohort 2
n=6 participants at risk
Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1.
Sapropterin: Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1.
|
|---|---|---|
|
General disorders
Post LP Headache
|
33.3%
2/6 • Number of events 2 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
50.0%
3/6 • Number of events 4 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
Viral Illness
|
33.3%
2/6 • Number of events 2 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
50.0%
3/6 • Number of events 3 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
Gastrointestinal disorders
GI illness
|
0.00%
0/6 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
Headache
|
33.3%
2/6 • Number of events 3 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
root canal
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
0.00%
0/6 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
Limb Trauma
|
0.00%
0/6 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
Pain
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
33.3%
2/6 • Number of events 2 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
|
General disorders
Depression
|
0.00%
0/6 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
16.7%
1/6 • Number of events 1 • Per protocol, adverse event data was collected from Baseline visit to 24 week Extension Visit
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place