Clinical trial NCT00924703: Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Phenylketonuria
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2009-06-19
Enrollment: 68
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in the Blood Phenylalanine (Phe) Concentration
timeFrame: At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240
Secondary outcomes:
measure: Pharmacokinetics-Plasma Pegvaliase Concentration
timeFrame: At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 109 months.
measure: Percentage of Participants With Positive PEG IgG Antibody
timeFrame: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156
measure: Percentage of Participants With Positive PAL IgG Antibody
timeFrame: At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156
Other outcomes:
Locations:
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital
state: Illinois
city: Louisville
country: United States
facility: University of Louisville, Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Center for Applied Research Sciences
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.