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

NCT ID: NCT00924703

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-13
• Study Completion Date: 2019-01-31

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.

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.

Conditions

Phenylketonuria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rAvPAL-PEG

rAvPAL-PEG in varying doses dependent on safety and efficacy.

Group Type: EXPERIMENTAL

rAvPAL-PEG

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Pegvaliase

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

The Children's Hospital

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Ann and Robert H Lurie Children's Hospital

Chicago, Illinois, United States

University of Louisville, Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Missouri

Columbia, Missouri, United States

Washington University Center for Applied Research Sciences

St Louis, Missouri, United States

Nebraska Medical Center

Omaha, Nebraska, United States

Albany Medical Center

Albany, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Burton BK, Longo N, Vockley J, Grange DK, Harding CO, Decker C, Li M, Lau K, Rosen O, Larimore K, Thomas J; PAL-002 and PAL-004 Investigators. Pegvaliase for the treatment of phenylketonuria: Results of the phase 2 dose-finding studies with long-term follow-up. Mol Genet Metab. 2020 Aug;130(4):239-246. doi: 10.1016/j.ymgme.2020.06.006. Epub 2020 Jun 16.

Reference Type: DERIVED

PMID: 32593547 (View on PubMed)

Longo N, Zori R, Wasserstein MP, Vockley J, Burton BK, Decker C, Li M, Lau K, Jiang J, Larimore K, Thomas JA. Long-term safety and efficacy of pegvaliase for the treatment of phenylketonuria in adults: combined phase 2 outcomes through PAL-003 extension study. Orphanet J Rare Dis. 2018 Jul 4;13(1):108. doi: 10.1186/s13023-018-0858-7.

Reference Type: DERIVED

PMID: 29973227 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PAL-003

Identifier Type: -

Identifier Source: org_study_id