Long-Term Extension of Phase 2 Protocols of rAvPAL-PEG in Subjects With PKU (PAL-003)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00924703
First received: June 18, 2009
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

This study is an extension of the dose-finding study (PAL-002), and also as an extension for the dose and frequency finding study (PAL-004). 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 Intervention Phase
Phenylketonuria
Drug: rAvPAL-PEG
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Blood Phe concentrations [ Time Frame: 3 days postdose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety based on the incidence of adverse events and clinically significant changes in vital signs [ Time Frame: Screening and weekly thereafter ] [ Designated as safety issue: Yes ]
  • Antibody response [ Time Frame: Week 1 and monthly thereafter (eg. Week 4, 8, etc.) ] [ Designated as safety issue: No ]
    The presence of antibodies will be assessed.

  • Pharmacokinetics [ Time Frame: Week 1 and weekly thereafter ] [ Designated as safety issue: No ]
    Plasma concentrations of rAvPAL-PEG will be measured when steady-state levels of Phe are attained.

  • Safety based on clinically significant changes in laboratory test results [ Time Frame: Screening and monthly thereafter ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2010
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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, considering each subject's individual responses related to safety and efficacy.
Other Name: Phenylalanine ammonia lyase

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.

  Eligibility

Ages Eligible for Study:   16 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have completed participation in PAL-002, PAL-004 or 165-205.
  • 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 PAL-002.
  • Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
  • Creatinine > 1.5 times the upper limit of normal.
  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: NCT00924703

Locations
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, 60614
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, 65201
Washington University Center for Applied Research Sciences
St. 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, 15213
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Celeste Decker, MD BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT00924703     History of Changes
Other Study ID Numbers: PAL-003
Study First Received: June 18, 2009
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

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 18, 2014