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Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00924703
Recruitment Status : Completed
First Posted : June 19, 2009
Results First Posted : October 12, 2021
Last Update Posted : October 12, 2021
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief Summary:
This study is an extension of previous rAvPAL-PEG studies. Administration of rAvPAL-PEG will be continued to assess whether long-term dosing of rAvPAL-PEG is safe and can maintain reduced blood Phe concentrations in PKU subjects.

Condition or disease Intervention/treatment Phase
Phenylketonuria Drug: rAvPAL-PEG Phase 2

Detailed Description:
PAL-003 is designed to evaluate long-term treatment of subjects who are continuing to take rAvPAL-PEG. Subjects'previous rAvPAL-PEG dosing will continue in PAL-003. In PAL-003, each subject's dose will be adjusted as needed to attain or maintain blood Phe concentrations of 60-600 µmol/L. rAvPAL-PEG dose will be based on either a subject's weight or will be a fixed dose (subjects who have maintained blood Phe levels to 60-600 µmol/L for at least 2 consecutive weeks and who have maintained a stable rAvPAL-PEG dose for at least 2 consecutive weeks). Doses will be evaluated on an individual basis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Long-term Extension of a Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous Doses of rAvPAL-PEG in Subjects With PKU
Actual Study Start Date : January 13, 2010
Actual Primary Completion Date : January 31, 2019
Actual Study Completion Date : January 31, 2019

Arm Intervention/treatment
Experimental: rAvPAL-PEG
rAvPAL-PEG in varying doses dependent on safety and efficacy.
Drug: rAvPAL-PEG
The doses are planned to be in the same range as those tested in PAL-002 or PAL-004 and then modified either by increasing or decreasing the dose, adhering to an upper limit up to 5.0 mg/kg per week or 375 mg/week, considering each subject's individual responses related to safety and efficacy.
Other Name: Pegvaliase

Primary Outcome Measures :
  1. Change From Baseline in the Blood Phenylalanine (Phe) Concentration [ Time Frame: At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240 ]
    Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)

Secondary Outcome Measures :
  1. Pharmacokinetics-Plasma Pegvaliase Concentration [ Time Frame: At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240 ]
    Steady-state Pharmacokinetics (PK) of pegvaliase was measured in subjects who have achieved and maintained target blood Phe

  2. Number of Subjects With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 109 months. ]
    A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase (PAL-003)

  3. Percentage of Participants With Positive PEG IgG Antibody [ Time Frame: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156 ]
    The presence of IgG Antibodies against PEG (polyethylene glycol) is measured overtime

  4. Percentage of Participants With Positive PAL IgG Antibody [ Time Frame: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156 ]
    The presence of IgG Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must have completed participation in previous rAvPAL-PEG studies.
  • 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.
  • 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.
  • Maintained a stable diet.
  • 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 (with the exception of rAvPAL-PEG) or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • Use of any medication that is intended to treat PKU within 14 days prior to the administration of study drug.
  • Use or planned use of any injectable drugs containing PEG (other than rAvPAL-PEG), including Depo-Provera during study participation.
  • A prior reaction that included systemic symptoms (eg, generalized hives, respiratory or gastrointestinal problems, hypotension, angioedema, anaphylaxis) to rAvPAL-PEG or a PEG-containing product.
  • 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 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, including hypersensitivity reactions that necessitated early termination from previous rAvPAL-PEG studies.
  • Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
  • Creatinine > 1.5 times the upper limit of normal.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00924703

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United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Illinois
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, United States, 60611
United States, Kentucky
University of Louisville, Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65212
Washington University Center for Applied Research Sciences
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15224
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84108
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Director, MD BioMarin Pharmaceutical
  Study Documents (Full-Text)

Documents provided by BioMarin Pharmaceutical:
Study Protocol  [PDF] March 31, 2017
Statistical Analysis Plan  [PDF] April 27, 2016

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT00924703    
Other Study ID Numbers: PAL-003
First Posted: June 19, 2009    Key Record Dates
Results First Posted: October 12, 2021
Last Update Posted: October 12, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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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