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

NCT00924703 | Completed Phase 2 Results DMC

• 1 other identifier: PAL-003
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 14

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.

Conditions

Phenylketonuria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Pharmacokinetics-Plasma Pegvaliase Concentration

  At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

  Up to 109 months.

• Percentage of Participants With Positive PEG IgG Antibody

  At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

• Percentage of Participants With Positive PAL IgG Antibody

  At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

Study Arms (1)

rAvPAL-PEG

EXPERIMENTAL

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

Drug: rAvPAL-PEG

Interventions

rAvPAL-PEG 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.

Also known as: Pegvaliase

rAvPAL-PEG

Eligibility Criteria

• Age: 16 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (14)

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Ann and Robert H Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

University of Louisville, Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Washington University Center for Applied Research Sciences

St Louis, Missouri, 63110, United States

Location

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84108, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 32593547 DERIVED

• 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.

  PMID: 29973227 DERIVED

MeSH Terms

Conditions

Phenylketonurias

Interventions

pegvaliase

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Debra Lounsbury/Sr Principle Scientist, Clinical Sciences
• Organization: BioMarin Pharmaceutical Inc.

Dlounsbury@bmrn.com

415-506-6348

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: June 19, 2009
• Study Start: January 13, 2010
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)