PAL-003: 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
|Principal Investigator: NicolaLongo|
|Keywords: PKU , phenylketonuria , PEG-PAL||Department: Pediatric Genetics|
|IRB Number: 00036245||Co Investigator: DaveViskochil|
|Specialty: Pediatric Genetics|
|Sub Specialties: Medical Genetics|
The need exists for a treatment that will help individuals with phenylketonuria (PKU) safely achieve lifelong, reliable control of blood phenylalanine (Phe) concentrations and improve functional outcomes. PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (rAvPAL-PEG) is a potential substitute for the phenylalanine hydroxylase (PAH) enzyme, which is defective in individuals with PKU. rAvPAL-PEG may control blood Phe concentrations, which may have additional clinical benefits. This study is an extension of the rAvPAL-PEG Phase 2 studies PAL-002, PAL-004, and 165-205. 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.
Blood Phe levels depend not only on the functional presence of the endogenous enzyme PAH but also on the dietary intake of Phe. It is important to understand the role of diet on blood Phe levels concurrent with the administration of rAvPAL-PEG treatment. Therefore, an exploratory objective has been added to this study to assess the relationship of diet, rAvPAL-PEG administration, and blood Phe level. Changes to subject diet are not allowed in this study unless per the Investigator in consultation with the Sponsor’s Medical Officer. Diet will be monitored using a diet diary.
The primary objective of the study is:
Must have completed participation and all protocol-defined study drug regimens in PAL-002 or PAL-004.
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. For subjects with a legally authorized representative, this representative may provide consent for the subject.
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 two acceptable methods of contraception while participating in the study. Males post vasectomy for 2 years with no known pregnancies do not need to use any other forms of contraception during 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.
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 other than rAvPAL-PEG 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 6 months prior to Screening and 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. Subjects 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. However, subjects who discontinued from study treatment early due to a reaction are not eligible to enroll into this study.
Pregnant or breastfeeding at Screening. 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).
Pregnant females are allowed to remain in the study, but not allowed to receive the study drug (observation only).
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 PAL-002 or PAL-004
Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
Creatinine > 1.5 times the upper limit of normal.