A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks

NCT01560286 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 165-205
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

The primary objective of the study is to evaluate the effect of dosing regimens of multiple subcutaneous (SC) doses of rAvPAL-PEG to induce an early and sustained Phe reduction while decreasing the frequency and severity of hypersensitivity reactions in patients with PKU.

Conditions

Phenylketonuria

Keywords

PKU; Injections; PEG-PAL; PAL

Outcome Measures

Primary Outcomes (1)

• Blood Phenylalanine Concentration

  All patients will have their plasma Phenylalanine (Phe) assessed. Please note that "Pharmacokinetics Sub-study" was not performed, and thus no results are available.

  Baseline, Week 24

Secondary Outcomes (9)

• Number of Participants With Study Drug Related Adverse Events

  Minimum Weekly Assessment of Injection Sites, Vital Signs and Adverse Events. Other Safety Assessments will be performed at other intervals (below):

• Percentage of Participants With Positive Anti-PAL Immunoglobulin G [IgG]

  Baseline, Week 24

• Trough Concentration of BMN 165

  Week 1, Week 24

• Percentage of Participants With Positive Anti-PEG IgG

  Baseline, Week 24

• Percentage of Participants With Positive PAL-IgM

  Baseline, Week 24

Study Arms (1)

Group 1

EXPERIMENTAL

4-8 week induction of rAvPAL-PEG at 2.5 mg, followed by titration to maintenance dose

Biological: BMN 165 (rAvPAL-PEG)

Interventions

BMN 165 (rAvPAL-PEG) BIOLOGICAL

Subcutaneous injection of rAvPAL-PEG administered from 1 time up to 5 times per week between 2.5mg up to a maximum of 375mg for 24 weeks.

Also known as: Recombinant Anabaena variabilis phenylalanine ammonia lyase

Group 1

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:

• A diagnosis of PKU, with the following:
• Current blood Phe concentration of ≥ 600 µmol/L at Screening.
• Average blood Phe concentration of ≥ 600 µmol/L over the past 6 months, using available data.
• Naïve to prior treatment with rAvPAL-PEG.
• Evidence that the patient is a non responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan, insufficient response per investigator determination, unsuitable for Kuvan® per Investigator determination, and treatment end date ≥ 2 days prior to Day 1 \[ie, first dose\]). Patients 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 after the nature of the study has been explained and prior to any research-related procedures. In the case of participants under the age of 18 or participants who have been deemed mentally unable to provide informed consent, a parent or legal guardian may provide written informed consent (and, if required, the patient will provide written assent).
• Willing and able to comply with all study procedures.
• Between the ages of 16 and 70 years, inclusive.
• 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 patients must be willing to use an acceptable method of contraception while participating in the study.
• Maintained a stable diet with no significant modifications during the 4 weeks preceding the administration of study drug and willing to continue with the diet while on study so as to avoid potential variability of response due to variations in dietary intake.
• 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 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, including use of large amino acids, within 2 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.
• A prior reaction that included systemic symptoms (eg, respiratory or gastrointestinal problems, hypotension, angioedema, anaphylaxis) to a PEG containing product. Patients with a prior systemic reaction of generalized rash may be eligible for participation per the discretion of the Principal Investigator in consultation with the Sponsor's Medical Officer.
• 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 patient 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.
• A positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen and hepatitis C antibody.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (6)

The Children's Hospital

Aurora, Colorado, 80048, United States

Location

University of Florida, Gainesville

Gainesville, Florida, 32610, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

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: Sr. Medical Director, Clinical Science
• Organization: BioMarin Pharmaceutical Inc

Ari.Gershman@bmrn.com

415-475-5854

Study Officials

• Debra Lounsbury

  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: March 5, 2012
• First Posted: March 22, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: July 1, 2015
• Last Updated: August 6, 2019
• Results First Posted: February 27, 2019

Record last verified: 2019-07

Locations

US (6)