Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU)

NCT01212744 | Completed Phase 2 Results DMC

• 1 other identifier: PAL-004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate the effect of daily administration of rAvPAL-PEG on the reduction of blood Phe concentrations in subjects with PKU.

Conditions

Phenylketonuria

Keywords

PEG PAL; PKU; injection;

Outcome Measures

Primary Outcomes (1)

• Blood Phenylalanine Concentration

  Plasma Phe

  Baseline, Week 16

Secondary Outcomes (9)

• Study Drug Related Adverse Events

  Weekly

• Percentage of Participants With PAL IgG Antibody Percentage of Participants With Positive PAL IgG

  Baseline, Week 16

• Plasma Concentrations of rAvPAL-PEG (BMN 165)

  Baseline, Week 8, Week 13

• Percentage of Participants With PEG-IgG Antibody Positivity

  Baseline, Week 16

• Percentage of Participants With PAL-IgM Antibody Positivity

  Baseline, Week 16

Study Arms (1)

rAvPAL-PEG

EXPERIMENTAL

rAvPAL-PEG in varying doses

Drug: rAvPAL-PEG

Interventions

rAvPAL-PEG DRUG

0.06 mg/kg/day, 0.1 mg/kg/day, 0.2 mg/kg/day, 0.4 mg/kg/day, 0.6 mg/kg/day, 0.8 mg/kg/day

Also known as: Recombinant Anabaena variabilis phenylalanine ammonia lyase

rAvPAL-PEG

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PKU with both of the following: current blood Phe concentration of ≥ 600 micromol/L at screening and average blood Phe concentration of ≥ 600 micromol/L over the past 3 years, using available data
• Evidence that the subject is a non-responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan, insufficient response per investigator determination, and treatment end date ≥ 14 days prior to Day 1 \[ie, first dose\]). Subjects who have had a previous response to Kuvan® treatment but are not currently taking Kuvan® because of noncompliance and have been off treatment for ≥ 4 months prior to screening are eligible for participation.
• 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 legally authorized representative, 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.
• Between the ages of 16 and 70 years, inclusive.
• Negative pregnancy test at screening and willing to have additional pregnancy tests performed during the study for females of childbearing potential only. Females considered not of childbearing potential are those who have been in menopause for at least 2 years or have had a tubal ligation at least 1 year prior to screening, or who have had a total hysterectomy.
• Willing to use an acceptable method of contraception while participating in the study (sexually active subjects only).
• Maintained a stable diet with no significant modifications during the 4 weeks preceding the administration of study drug.
• In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and ECG at screening.

You may not qualify if:

• Prior use of rAvPAL-PEG.
• Use of any investigational product 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, within 3 months prior to screening and during study participation.
• Known hypersensitivity to rAvPAL-PEG excipients.
• 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 investigator, places the subject at high risk of poor treatment compliance or of not completing the study.
• 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 (9)

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Weisskopf Child Evaluation Center / University of Louisville

Louisville, Kentucky, 40202, 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

Albany Medical Center

Albany, New York, 12208, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53705, United States

Location

Related Publications (1)

• 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

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: Medical Director
• Organization: BioMarin Pharmaceutical Inc.

ari.gershman@bmrn.com

415-475-5854

Study Officials

• Ari Gershman, 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: September 29, 2010
• First Posted: October 1, 2010
• Study Start: March 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: February 26, 2019
• Results First Posted: February 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)