Tetrahydrobiopterin DeficienciesPhase 2NCT00355264
Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency
A Phase 2 study testing Phenoptin in people with Tetrahydrobiopterin Deficiencies and Hyperphenylalaninemia, Non-Phenylketonuric, run by BioMarin Pharmaceutical at 10 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tetrahydrobiopterin Deficiencies, Hyperphenylalaninemia, Non-Phenylketonuric
- What is being tested?
- Phenoptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Aug 2006to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented history of blood Phe level > 180 µmol/L on at least one occasion
- Established diagnosis of hyperphenylalaninemia (HPA) due to primary BH4 deficiency with a documented defect in biopterin metabolism with blood or urine tests
- Willing and able to provide written informed consent or, in the case of subjects under the age of 18 years, provide written assent (if required) and written informed consent by a parent or legal guardian
- Negative urine pregnancy test at screening for females of child-bearing potential
- Male and female subjects of childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures and be willing to continue to use acceptable birth control measures, as determined by the Investigator, and be willing to continue to use acceptable birth control measures while participating in the study
- Willing and able to comply with all study procedures
- Able to take medication orally
Who cannot join
- Perceived to be unreliable or unavailable for study participation or, if under the age of 18 years, have parents or legal guardians who are perceived to be unreliable or unavailable
- Use of any investigational agent (other than BH4) within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments
- Positive urine pregnancy test at screening (non-sterile females of child bearing potential only), already known to be pregnant or breastfeeding or planning a pregnancy in self or partner during the study
- Female subjects of childbearing potential not using an effective method of birth control, as determined by the PI, or unwilling to continue to use acceptable birth control measures.
- Alanine aminotransferase (ALT) > 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health Organization Toxicity Criteria) at screening
- Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation)
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- Serious neuropsychiatric illness (e.g., major depression) not currently under medical control
- Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate)
- Clinical diagnosis of phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency
- Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing the study
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
Study site
Chapel Hill, North Carolina, 27599
Study site
Chicago, Illinois, 60614
Study site
Los Angeles, California, 90095
Study site
Madison, Wisconsin, 53705
Study site
Minneapolis, Minnesota, 55455
Study site
New York, New York, 10029
Study site
Portland, Oregon, 97239
Study site
Salt Lake City, Utah, 84132
Study site
Seattle, Washington, 98105
About this study
Official title: Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population. Some subjects were receiving non-registered formulations of BH4 at enrollment and this treatment was suspended after Part 1 and within one day the subjects started Phenoptin at approximately the same dose.
Read the detailed description
Within 4 weeks of completing screening assessments to determine eligibility, subjects will be enrolled in the study. The study will be conducted in two parts.
Part 1: After screening, all subjects will be followed for two weeks without modification of their baseline medical or dietary care.
Part 2: Beginning at Week 2, subjects who were receiving non-registered formulations of BH4 at enrollment will suspend this treatment and within one day will start Phenoptin at approximately the same dose of the non-registered BH4 formulation. Subjects not receiving BH4 at enrollment will begin treatment with Phenoptin at approximately 5 mg/kg/day, given orally, prior to meals.
At the discretion of the Investigator, the Phenoptin dose may be adjusted up or down at the Week 6 visit to control blood Phe levels (<360 µmol/L), or to optimize the clinical effect. The maximum dose allowed will be approximately 20 mg/kg/day. All subjects will receive Phenoptin for a total of 8 weeks. Subjects will be instructed to continue their usual diet without modification. Study visits will occur every other week.
Tyrosine, biopterin and neopterin will be analyzed at the following visits: Week 0 (enrollment), Week 2 (prior to dosing with Phenoptin), Week 8 (after 6 weeks of treatment with Phenoptin) and Week 10 (after 8 weeks of treatment with Phenoptin).During each visit, blood Phe level will be measured (2.5-5 hours after a meal), and safety evaluations will be performed. Safety will be assessed by monitoring adverse events and vital signs, performing physical examinations, assessing signs and symptoms of primary BH4 deficiency (i.e., neurological symptoms such as seizures, changes in muscle tone, weakness, etc.) and clinical laboratory tests (chemistry, hematology and urinalysis).
Extension: Upon completion of 8 weeks of treatment (i.e., at the Week 10 visit), subjects will be offered the option to continue treatment with Phenoptin in an extension of this study. Participation in the study extension will continue until one of the following occurs:
- the subject withdraws consent and discontinues from the study,
- the subject is discontinued from the study at the discretion of the investigator,
- the study drug is available through the appropriate marketing approval, or
- the study is terminated.
During the extension period, study drug will be dispensed to subjects monthly, and study visits will be required every 3 months. The Phenoptin dose may be adjusted at any visit during the study extension at the discretion of the Investigator. The maximum dose allowed will be approximately 20 mg/kg/day.
- Being tested
- Phenoptin
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenoptinDrug
5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels
| Study group | Role | What they receive |
|---|---|---|
| Single Arm on Active Drug | Experimental | 5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels
Outcomes were also evaluated by the subject's type of BH4 deficiency either defects in the genes encoding the enzymes involved in biosynthesis or defects in the genes encoding the enzymes involved in recycling. Receives: Drug: Phenoptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The ideal range for blood Phe levels is approximately 120-360 µmol/L.
Measured: At Baseline, Week 4 through Extension Week 130
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The objective of this outcome was to compare to Phe levels achieved using previous treatment regimens.
Measured: At Baseline, Week 4 through Extension Week 130
Secondary outcomes (1)
Subjects Experiencing Adverse Events(AEs)
Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied.
Mild = AE did not limit usual activities.
Moderate = AE resulted in some limitation of usual activities.
Severe = AE resulted in an inability to carry out usual activities.
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Serious AE (SAE) resulted in death, was life-threatening, required in patient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect; or was an important medical event.
Measured: Up to 35 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2006 (estimated)
- Study startAug 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tetrahydrobiopterin DeficienciesStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Outcomes were to be evaluated for all subjects with primary BH4 disease. Outcomes were also evaluated based on the type of BH4 deficiency either due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, GTPcyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR); or defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR)
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355264
- Sponsor's protocol ID
- PKU-007
- Status last verified
- Sep 2020
- First submitted
- 19 Jul 2006
- Last updated
- 25 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency
- ClinicalTrials.gov ID
- NCT00355264
- Acronym / sponsor ID
- PKU-007
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 21 Jul 2006 (estimated)
- Results
- Posted 25 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population. Some subjects were receiving non-registered formulations of BH4 at enrollment and this treatment was suspended after Part 1 and within one day the subjects started Phenoptin at approximately the same dose.
Detailed description
Within 4 weeks of completing screening assessments to determine eligibility, subjects will be enrolled in the study. The study will be conducted in two parts.
Part 1: After screening, all subjects will be followed for two weeks without modification of their baseline medical or dietary care.
Part 2: Beginning at Week 2, subjects who were receiving non-registered formulations of BH4 at enrollment will suspend this treatment and within one day will start Phenoptin at approximately the same dose of the non-registered BH4 formulation. Subjects not receiving BH4 at enrollment will begin treatment with Phenoptin at approximately 5 mg/kg/day, given orally, prior to meals.
At the discretion of the Investigator, the Phenoptin dose may be adjusted up or down at the Week 6 visit to control blood Phe levels (<360 µmol/L), or to optimize the clinical effect. The maximum dose allowed will be approximately 20 mg/kg/day. All subjects will receive Phenoptin for a total of 8 weeks. Subjects will be instructed to continue their usual diet without modification. Study visits will occur every other week.
Tyrosine, biopterin and neopterin will be analyzed at the following visits: Week 0 (enrollment), Week 2 (prior to dosing with Phenoptin), Week 8 (after 6 weeks of treatment with Phenoptin) and Week 10 (after 8 weeks of treatment with Phenoptin).During each visit, blood Phe level will be measured (2.5-5 hours after a meal), and safety evaluations will be performed. Safety will be assessed by monitoring adverse events and vital signs, performing physical examinations, assessing signs and symptoms of primary BH4 deficiency (i.e., neurological symptoms such as seizures, changes in muscle tone, weakness, etc.) and clinical laboratory tests (chemistry, hematology and urinalysis).
Extension: Upon completion of 8 weeks of treatment (i.e., at the Week 10 visit), subjects will be offered the option to continue treatment with Phenoptin in an extension of this study. Participation in the study extension will continue until one of the following occurs:
- the subject withdraws consent and discontinues from the study,
- the subject is discontinued from the study at the discretion of the investigator,
- the study drug is available through the appropriate marketing approval, or
- the study is terminated.
During the extension period, study drug will be dispensed to subjects monthly, and study visits will be required every 3 months. The Phenoptin dose may be adjusted at any visit during the study extension at the discretion of the Investigator. The maximum dose allowed will be approximately 20 mg/kg/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Outcomes were to be evaluated for all subjects with primary BH4 disease. Outcomes were also evaluated based on the type of BH4 deficiency either due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, GTPcyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR); or defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR)
| Arm | Type | Receives |
|---|---|---|
| Single Arm on Active Drug | Experimental | Drug: Phenoptin5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels Outcomes were also evaluated by the subject's type of BH4 deficiency either defects in the genes encoding the enzymes involved in biosynthesis or defects in the genes encoding the enzymes involved in recycling. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Documented history of blood Phe level > 180 µmol/L on at least one occasion
- Established diagnosis of hyperphenylalaninemia (HPA) due to primary BH4 deficiency with a documented defect in biopterin metabolism with blood or urine tests
- Willing and able to provide written informed consent or, in the case of subjects under the age of 18 years, provide written assent (if required) and written informed consent by a parent or legal guardian
- Negative urine pregnancy test at screening for females of child-bearing potential
- Male and female subjects of childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures and be willing to continue to use acceptable birth control measures, as determined by the Investigator, and be willing to continue to use acceptable birth control measures while participating in the study
Key exclusion criteria (10 listed)
- Perceived to be unreliable or unavailable for study participation or, if under the age of 18 years, have parents or legal guardians who are perceived to be unreliable or unavailable
- Use of any investigational agent (other than BH4) within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments
- Positive urine pregnancy test at screening (non-sterile females of child bearing potential only), already known to be pregnant or breastfeeding or planning a pregnancy in self or partner during the study
- Female subjects of childbearing potential not using an effective method of birth control, as determined by the PI, or unwilling to continue to use acceptable birth control measures.
- Alanine aminotransferase (ALT) > 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health Organization Toxicity Criteria) at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phenoptin5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels | Drug | Single Arm on Active Drug |
Primary outcome
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Time frame: At Baseline, Week 4 through Extension Week 130
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The ideal range for blood Phe levels is approximately 120-360 µmol/L.
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Time frame: At Baseline, Week 4 through Extension Week 130
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The objective of this outcome was to compare to Phe levels achieved using previous treatment regimens.
1 secondary outcome
Subjects Experiencing Adverse Events(AEs)
Time frame: Up to 35 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Phenoptin in people with Tetrahydrobiopterin Deficiencies and Hyperphenylalaninemia, Non-Phenylketonuric, run by BioMarin Pharmaceutical at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints (time frame: At Baseline, Week 4 through Extension Week 130). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.