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Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00634660
First received: March 6, 2008
Last updated: January 30, 2017
Last verified: January 2017
  Purpose
The purpose of this study is to assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU.

Condition Intervention Phase
Phenylketonuria Drug: rAvPAL-PEG Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • • 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.


Secondary Outcome Measures:
  • • To evaluate the pharmacokinetics (PK) of single, SC injections of rAvPAL-PEG administered at escalating doses, in subjects with PKU. [ Time Frame: 6 weeks ]
    Specifically, exposure, AUC- and Cmax -dose proportionality, Tmax , λz and t1/2

  • • To evaluate the effect of different dose levels of rAvPAL-PEG on blood Phe concentrations in subjects with PKU. [ Time Frame: 6 weeks ]
    Specifically, exposure, AUC- and Cmax -dose proportionality, Tmax , λz and t1/2


Enrollment: 25
Study Start Date: May 2008
Study Completion Date: October 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 0.001 mg/kg
One subcutaneous injection of 0.001 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 0.003 mg/kg
One subcutaneous injection of 0.003 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 0.01 mg/kg
One subcutaneous injection of 0.01 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 0.03 mg/kg
One subcutaneous injection of 0.03 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 0.1 mg/kg
One subcutaneous injection of 0.1 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 0.3 mg/kg
One subcutaneous injection of 0.3 mg/kg of rAvPAL-PEG.
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.
Active Comparator: 1.0 mg/kg
One subcutaneous injection of 1.0 mg/kg of rAvPAL-PEG.
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.

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).
  Eligibility

Ages Eligible for Study:   16 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634660

Locations
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University Center for Applied Research Sciences
St. Louis, Missouri, United States, 63110
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Celeste Decker, MD BioMarin Pharmaceutical
  More Information

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT00634660     History of Changes
Other Study ID Numbers: PAL-001
Study First Received: March 6, 2008
Last Updated: January 30, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on September 19, 2017