Conditions: Phenylketonuria
Keywords: PKU PEG PAL BioMarin
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 40
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate whether weekly injections of phenylalanine ammonia lyase (rAvPAL-PEG) can reduce blood phenylalanine concentrations in PKU subjects and whether repeated administration is safe.

Detailed description:
This is a 2 part, Phase 2, open-label dose-finding study in approximately 35 subjects with PKU. Seven dose cohorts are planned, each consisting of 5 subjects. In Part 1, the planned starting dose levels are those tested in PAL 001 (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg), provided no dose limiting toxicity was observed in PAL 001. In Parts 1 and 2, study drug will be administered by clinic staff.

Subjects who completed participation in PAL 001 will receive priority to participate in PAL 002. rAvPAL PEG naïve subjects will be enrolled to fill any dose cohort vacancies resulting from subjects who did not complete PAL 001 or who chose not to continue into PAL 002. In addition, if the number of dose cohorts determined in PAL 001 is less than 7, additional naïve subjects may be added to the existing dose cohorts to provide a total of approximately 35 subjects entering Part 1 of PAL 002. Furthermore, if serial dosing of cohorts in Part 1 of PAL 002 is stopped, additional subjects (either naïve subjects or PAL 001 subjects) may be added to the existing cohorts so that total study enrollment is approximately 35 subjects. In any of these cases, additional subjects will be enrolled sequentially from lowest to highest dose cohort.

Diet will not be altered during the course of this study, except as necessary for safety.

Subjects will be evaluated for safety and for blood Phe concentrations throughout the study. Toxicity will be measured according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.

A Data Monitoring Committee will monitor the study.

Arms:
arm 1: Subjects will start on rAvPAL-PEG 0.001 mg/kg arm 2: Subjects will start on rAvPAL-PEG 0.003 mg/kg arm 3: Subjects will start on rAvPAL-PEG 0.01 mg/kg arm 4: Subjects will start on rAvPAL-PEG 0.03 mg/kg arm 5: Subjects will start on rAvPAL-PEG 0.1 mg/kg

Interventions: intervention 1: rAvPAL-PEG 0.001 mg/kg intervention 2: rAvPAL-PEG 0.003 mg/kg intervention 3: rAvPAL-PEG 0.01 mg/kg intervention 4: rAvPAL-PEG 0.03 mg/kg intervention 5: rAvPAL-PEG 0.1 mg/kg
Intervention descriptions: intervention 1: In Part 1, the planned starting dose levels is 0.001 mg/kg intervention 2: In Part 1, the planned starting dose levels is 0.003 mg/kg intervention 3: In Part 1, the planned starting dose levels is 0.01 mg/kg intervention 4: In Part 1, the planned starting dose levels is 0.03 mg/kg intervention 5: In Part 1, the planned starting dose levels is 0.1 mg/kg

Protocol document: