Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria

Phenylketonuria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634660
• Other study ID #: PAL-001
• Status: Completed
• Phase: Phase 1
• First received: March 6, 2008
• Last updated: January 30, 2017
• Start date: May 2008
• Est. completion date: October 2009

Study information

• Verified date: January 2017
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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.

• 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.

Exclusion Criteria:

• 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.

• 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).

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

Drug:
• rAvPAL-PEG
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.

Locations

Country	Name	City	State
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Mount Sinai Medical Center	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Washington University Center for Applied Research Sciences	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• 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.	6 weeks
Secondary	• 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 , ?z and t1/2	6 weeks
Secondary	• 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 , ?z and t1/2	6 weeks