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

Phenylketonuria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00924703
• Other study ID #: PAL-003
• Status: Completed
• Phase: Phase 2
• Start date: January 13, 2010
• Est. completion date: January 31, 2019

Study information

• Verified date: September 2021
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

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.

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	The Children's Hospital	Aurora	Colorado
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Ann and Robert H Lurie Children's Hospital	Chicago	Illinois
United States	University of Missouri	Columbia	Missouri
United States	University of Florida	Gainesville	Florida
United States	University of Louisville, Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mount Sinai School of Medicine	New York	New York
United States	Nebraska Medical Center	Omaha	Nebraska
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University Center for Applied Research Sciences	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Blood Phenylalanine (Phe) Concentration	Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)	At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240
Secondary	Pharmacokinetics-Plasma Pegvaliase Concentration	Steady-state Pharmacokinetics (PK) of pegvaliase was measured in subjects who have achieved and maintained target blood Phe	At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240
Secondary	Number of Subjects With Treatment Emergent Adverse Events (TEAEs)	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)	Up to 109 months.
Secondary	Percentage of Participants With Positive PEG IgG Antibody	The presence of IgG Antibodies against PEG (polyethylene glycol) is measured overtime	At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156
Secondary	Percentage of Participants With Positive PAL IgG Antibody	The presence of IgG Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime	At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156