Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01560286
Other study ID # 165-205
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date May 2012
Est. completion date July 2015

Study information

Verified date July 2019
Source BioMarin Pharmaceutical
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

The primary rationale for this study is to define an optimal rAvPAL-PEG dose regimen by establishing the therapeutic effect within the shortest time possible time for induction, titration and maintenance phases while reducing the severity and frequency of hypersensitivity reactions that may lead to dose interruptions. It is hypothesized that these goals can be achieved by keeping rAvPAL-PEG doses low when anti-PEG IgM response is predicted to be high and titrating to an efficacious dose once the IgG response to PAL has developed. Further investigation is needed to determine how early and quickly patients can titrate safely to lower blood Phe; therefore, this protocol proposes to assess two Groups using an induction/titration and maintenance schedule with an aim towards establishing the therapeutic effect safety within an optimal period of time.


Recruitment information / eligibility

Status Completed
Enrollment 24
Est. completion date July 2015
Est. primary completion date September 2013
Accepts healthy volunteers No
Gender All
Age group 16 Years to 70 Years
Eligibility Inclusion Criteria:

1. 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.

2. 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.

3. 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).

4. Willing and able to comply with all study procedures.

5. Between the ages of 16 and 70 years, inclusive.

6. 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.

7. Sexually active patients must be willing to use an acceptable method of contraception while participating in the study.

8. 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.

9. In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.

Exclusion Criteria:

1. 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.

2. 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.

3. 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.

4. 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.

5. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.

6. 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).

7. 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.

8. Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.

9. Creatinine > 1.5 times the upper limit of normal.

10. A positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen and hepatitis C antibody.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
BMN 165 (rAvPAL-PEG)
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.

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 University of Florida, Gainesville Gainesville Florida
United States Nebraska Medical Center Omaha Nebraska
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 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 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):
Secondary Percentage of Participants With Positive Anti-PAL Immunoglobulin G [IgG] Antibody Positivity Baseline, Week 24
Secondary Trough Concentration of BMN 165 PK assessment from pre-dose blood draw. Week 1, Week 24
Secondary Percentage of Participants With Positive Anti-PEG IgG Antibody Positivity Baseline, Week 24
Secondary Percentage of Participants With Positive PAL-IgM Antibody Positivity Baseline, Week 24
Secondary Percentage of Participants With Positive Anti-PEG-IgM Antibody positivity Baseline, Week 24
Secondary Percentage of Participants With Positive Neutralizing Antibodies [Nab] Antibody positivity Baseline, Week 24
Secondary Percentage of Participants With Positive Anti-PAL-IgE Antibodies Antibody positivity Baseline, Week 24
Secondary Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies Antibody positivity Baseline, Week 24
See also
  Status Clinical Trial Phase
Completed NCT05099640 - A Study of PTC923 in Participants With Phenylketonuria Phase 3
Completed NCT01924026 - Neurocognitive Outcomes in Mild Hyperphenylalaninemia (MHP)MHP Study N/A
Completed NCT01428258 - Phase 2 Study of Glycomacropeptide Versus Amino Acid Diet for Management of Phenylketonuria N/A
Completed NCT00925054 - Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU Phase 2
Completed NCT00778206 - PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry
Recruiting NCT05948020 - Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria N/A
Recruiting NCT05781399 - First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria Phase 1
Completed NCT02555579 - Simplified Diet Approach in Phenylketonuria N/A
Completed NCT03097250 - MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
Completed NCT01965912 - Kuvan®'s Effect on the Cognition of Children With Phenylketonuria Phase 4
Completed NCT01965691 - Protein Requirements in Children With Phenylketonuria (PKU) N/A
Completed NCT00688844 - Nutritional and Neurotransmitter Changes in PKU Subjects on BH4 N/A
Completed NCT00789568 - A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects Phase 1
Terminated NCT01465100 - Liver Cell Transplant for Phenylketonuria Phase 1/Phase 2
Completed NCT01732471 - Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria Phase 3
Completed NCT04879277 - Study of Low-grade Systemic Inflammation in Adult Patients With Phenylketonuria N/A
Completed NCT02176603 - Observational Study of Endothelial Dysfunction in Phenylketonuria N/A
Completed NCT01869972 - Biological Variation of Phenylalanine in Patients With Hyperphenylalaninemia N/A
Terminated NCT01904708 - Moderate Intensity Exercise and Phenylketonuria N/A
Completed NCT01819727 - An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 Phase 3