Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous (SC) Doses of rAvPAL-PEG in Subjects With PKU|
- Blood Phe concentrations [ Time Frame: Screening, Weeks 1-22 ] [ Designated as safety issue: No ]
- Safety [ Time Frame: Screening, Weeks 1-22 ] [ Designated as safety issue: Yes ]Safety will be evaluated on the incidence of AEs and clinically significant changes in vital signs and laboratory test results.
- Antibody response [ Time Frame: Periodically throughout the duration of the study (22 weeks) ] [ Designated as safety issue: No ]
- Pharmacokinetics [ Time Frame: Periodically throughout the duration of the study (22 weeks) ] [ Designated as safety issue: No ]Plasma concentrations of rAvPAL-PEG will be measured.
|Study Start Date:||September 2009|
|Study Completion Date:||June 2015|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Subjects will be given rAvPAL-PEG in varying doses not to exceed 5 mg/kg/week until efficacy is reached or until maximum tolerable dose has been reached.
In Part 1, the planned starting dose levels are those tested in PAL-001 (0.001, 0.003, 0.01, 0.03, and 0.1 mg/kg), provided no dose-limiting toxicity was observed in PAL-001. After each subject completes Part 1, the subject's rAvPAL-PEG dosing will continue in Part 2. In Part 2, each subject's dose will be adjusted to attain a target blood Phe concentration with target levels between 120-600 micromol/L and a minimum blood Phe concentration decrease of 30% from baseline.
Other Name: rAvPAL in varying doses determined by safety and efficacy.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00925054
|United States, Colorado|
|The Children's Hospital|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|Decatur, Georgia, United States, 30033|
|United States, Illinois|
|Children's Memorial Hospital|
|Chicago, Illinois, United States, 60614|
|United States, Minnesota|
|University of Minnesota Medical Center-Fairview|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Washington University Center for Applied Research Sciences|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Albany Medical Center|
|Albany, New York, United States, 12208|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|United States, Ohio|
|Akron Children's Hospital|
|Akron, Ohio, United States, 44308|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Utah|
|University of Utah Hospital|
|Salt Lake City, Utah, United States, 84132|
|Study Director:||Celeste Decker, MD||BioMarin Pharmaceutical|