PhenylketonuriaPhase 1NCT00634660
Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria
A Phase 1 study testing rAvPAL-PEG in people with Phenylketonuria, run by BioMarin Pharmaceutical at 8 sites in United States.
Trial summary
The purpose of this study is to assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU. Read more about this study
- Who is it for?
- Ages 16 to 50 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- rAvPAL-PEG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2008to Oct 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 16 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of PKU with both of the following:
- Current blood Phe concentration of ≥600 µmol/L at Screening.
- Average blood Phe concentration of ≥600 µmol/L over the past 3 years, using available data.
- Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures.
- Willing and able to comply with all study procedures.
- Between the ages of 16 and 50 years, inclusive.
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- Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
- Stable diet with no significant modifications during the 4 weeks preceding the administration of study drug.
- In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.
Who cannot join
- Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
- Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease).
- Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.
- Known hypersensitivity to rAvPAL PEG or its excipients.
- Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
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- Creatinine above the upper limit of normal.
- Donation of blood or plasma within 30 days prior to the administration of study drug.
- Use of any over-the-counter (OTC) medication, including vitamins, within 7 days prior to the administration of study drug, without evaluation and approval by the Investigator.
- Use of any prescription medication within 14 days prior to the administration of study drug without evaluation and approval by the Investigator.
- Treatment with any drug known to affect hepatic enzyme activity, including (but not limited to) barbiturates, phenothiazines, cimetidine, or carbamazepine, within 30 days prior to study drug administration.
- Use of any tobacco products within 60 days prior to study drug administration.
- Positive urine screen for use of nicotine (cotinine) or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, and opiates).
- Positive test or has been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Memorial Hospital
Chicago, Illinois, 60614
University of Wisconsin
Madison, Wisconsin, 53705
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
Mount Sinai Medical Center
New York, New York, 10029
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
University of Utah Hospital
Salt Lake City, Utah, 84132
Washington University Center for Applied Research Sciences
St Louis, Missouri, 63110
About this study
Official title: A Phase I, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Subcutaneous Doses of rAvPAL-PEG in Subjects With Phenylketonuria
The purpose of this study is to assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU.
Read the detailed description
This is a Phase 1, open-label, single-dose study in approximately 35 subjects with PKU who are 16 to 50 years old. Seven cohorts are planned, each consisting of 5 subjects; the cohorts as planned are 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. Increasing doses of rAvPAL-PEG will be assessed sequentially until the final dose is evaluated or any of the stopping criteria are reached. Subjects will each receive a single dose and then will be followed for a total of 42 days (6 weeks) with visits to the clinical research unit (CRU) as specified in the Schedule of Events Toxicity will be measured according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v 3).
- Conditions
- Phenylketonuria
- Being tested
- rAvPAL-PEG
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAvPAL-PEGDrug
rAvPAL-PEG will be administered as a single, SC injection at dose levels of 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. The duration of treatment is a single dose of study drug with 42 days (6 weeks) of follow-up.
| Study group | Role | What they receive |
|---|---|---|
| 0.001 mg/kg | Active comparator | One subcutaneous injection of 0.001 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 0.003 mg/kg | Active comparator | One subcutaneous injection of 0.003 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 0.01 mg/kg | Active comparator | One subcutaneous injection of 0.01 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 0.03 mg/kg | Active comparator | One subcutaneous injection of 0.03 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 0.1 mg/kg | Active comparator | One subcutaneous injection of 0.1 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 0.3 mg/kg | Active comparator | One subcutaneous injection of 0.3 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
| 1.0 mg/kg | Active comparator | One subcutaneous injection of 1.0 mg/kg of rAvPAL-PEG. Receives: Drug: rAvPAL-PEG |
What is being measured
The primary outcome is the main question the study is designed to answer.
• To assess the incidence of treatment-emergent adverse events of a single, subcutaneous (SC) injections of rAvPAL-PEG in subjects with PKU.
Specifically, safety was to be assessed by examining the incidence of all treatment-emergent adverse events reported during the study period and clinically significant changes in vital signs and clinical laboratory results, including development of rAvPAL-PEG antibodies.
Measured: 6 weeks
Secondary outcomes (2)
• To evaluate the pharmacokinetics (PK) of single, SC injections of rAvPAL-PEG administered at escalating doses, in subjects with PKU.
Specifically, exposure, AUC- and Cmax -dose proportionality, Tmax , λz and t1/2
Measured: 6 weeks
• To evaluate the effect of different dose levels of rAvPAL-PEG on blood Phe concentrations in subjects with PKU.
Specifically, exposure, AUC- and Cmax -dose proportionality, Tmax , λz and t1/2
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startMay 2008
- Primary completionApr 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Celeste Decker, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634660
- Sponsor's protocol ID
- PAL-001
- Status last verified
- Jan 2017
- First submitted
- 6 Mar 2008
- Last updated
- 1 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Subcutaneous Doses of rAvPAL-PEG in Subjects With Phenylketonuria
- ClinicalTrials.gov ID
- NCT00634660
- Acronym / sponsor ID
- PAL-001
- Conditions
- Phenylketonuria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Apr 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Not posted in the source record
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 assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU.
Detailed description
This is a Phase 1, open-label, single-dose study in approximately 35 subjects with PKU who are 16 to 50 years old. Seven cohorts are planned, each consisting of 5 subjects; the cohorts as planned are 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. Increasing doses of rAvPAL-PEG will be assessed sequentially until the final dose is evaluated or any of the stopping criteria are reached. Subjects will each receive a single dose and then will be followed for a total of 42 days (6 weeks) with visits to the clinical research unit (CRU) as specified in the Schedule of Events Toxicity will be measured according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v 3).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 0.001 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.001 mg/kg of rAvPAL-PEG. |
| 0.003 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.003 mg/kg of rAvPAL-PEG. |
| 0.01 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.01 mg/kg of rAvPAL-PEG. |
| 0.03 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.03 mg/kg of rAvPAL-PEG. |
| 0.1 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.1 mg/kg of rAvPAL-PEG. |
| 0.3 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 0.3 mg/kg of rAvPAL-PEG. |
| 1.0 mg/kg | Active comparator | Drug: rAvPAL-PEGOne subcutaneous injection of 1.0 mg/kg of rAvPAL-PEG. |
Who may qualify
- Ages
- 16 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Diagnosis of PKU with both of the following:
- Current blood Phe concentration of ≥600 µmol/L at Screening.
- Average blood Phe concentration of ≥600 µmol/L over the past 3 years, using available data.
- Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures.
- Willing and able to comply with all study procedures.
Key exclusion criteria (14 listed)
- Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
- Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease).
- Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.
- Known hypersensitivity to rAvPAL PEG or its excipients.
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 |
|---|---|---|
| rAvPAL-PEGrAvPAL-PEG will be administered as a single, SC injection at dose levels of 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. The duration of treatment is a single dose of study drug with 42 days (6 weeks) of follow-up. | Drug | 0.001 mg/kg, 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg |
Primary outcome
• To assess the incidence of treatment-emergent adverse events of a single, subcutaneous (SC) injections of rAvPAL-PEG in subjects with PKU.
Time frame: 6 weeks
Specifically, safety was to be assessed by examining the incidence of all treatment-emergent adverse events reported during the study period and clinically significant changes in vital signs and clinical laboratory results, including development of rAvPAL-PEG antibodies.
2 secondary outcomes
• To evaluate the pharmacokinetics (PK) of single, SC injections of rAvPAL-PEG administered at escalating doses, in subjects with PKU.
Time frame: 6 weeks
• To evaluate the effect of different dose levels of rAvPAL-PEG on blood Phe concentrations in subjects with PKU.
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2017.
- Individual participant dataSharing planned: No
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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.
Celeste Decker, MD study director
BioMarin Pharmaceutical
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rAvPAL-PEG in people with Phenylketonuria, run by BioMarin Pharmaceutical at 8 sites in United States.
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 10 inclusion and 14 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 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
• To assess the incidence of treatment-emergent adverse events of a single, subcutaneous (SC) injections of rAvPAL-PEG in subjects with PKU. (time frame: 6 weeks). 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 1 Feb 2017.