Phenylketonuria
Conditions
Keywords
PKU, PEG PAL, BioMarin
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.
Interventions
DRUGrAvPAL-PEG 0.001 mg/kg
In Part 1, the planned starting dose levels is 0.001 mg/kg
DRUGrAvPAL-PEG 0.003 mg/kg
In Part 1, the planned starting dose levels is 0.003 mg/kg
DRUGrAvPAL-PEG 0.01 mg/kg
In Part 1, the planned starting dose levels is 0.01 mg/kg
DRUGrAvPAL-PEG 0.03 mg/kg
In Part 1, the planned starting dose levels is 0.03 mg/kg
DRUGrAvPAL-PEG 0.1 mg/kg
In Part 1, the planned starting dose levels is 0.1 mg/kg
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* For subjects who did not participate in PAL-001, diagnosis of PKU with both of the following: Current blood Phe concentration of ≥ 600 mmol/L at Screening and average blood Phe concentration of ≥ 600 µmol/L over the past 3 years, using available data. * For subjects who did not participate in PAL-001, evidence that the subject is a non-responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan®, insufficient response per investigator determination, and treatment end date ≥ 14 days prior to Day 1 \[ie, first dose\]). Subjects who have had a previous response to Kuvan® treatment but are not currently taking Kuvan® because of noncompliance and have been off treatment for ≥ 6 months prior to Screening are eligible for participation. * Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures. * Between the ages of 16 and 55 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 subjects 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. * In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening. * Willing and able to comply with study procedures.
Exclusion criteria
* 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 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 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 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. * 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 subject 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Blood Phenylalanine Concentrations | Baseline, Week 1/Day 5, Week 7, Week 16/Day 106 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Drug Related Adverse Events | Screening, Weeks 1-22 | — |
| Number of Participants With Positive PAL IgG Antibody | Baseline, Week 12 | Antibody against PAL (phenylalanine ammonia lyase) measured over time |
| Number of Participants With Positive PAL IgM Antibody | Baseline, Week 12 | Antibody positivity over time |
| Number of Participants With Positive PEG IgM Antibody | Baseline, Week 16 | Antibody positivity over time |
| Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline, Week 12 | Antibody positivity over time |
| Percentage of Participants With Positive PAL IgE Antibody | Baselline, Week 12 | Antibody positivity over time |
| Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline, Week 12 | Antibody positivity over time |
| Number of Participants With Positive PEG IgG Antibody | Baseline, Week 16 | Antibody positivity over time |
Other
| Measure | Time frame | Description |
|---|---|---|
| Trough Concentration of BMN 165 | Baseline, Baseline/pre-dose, Week 7, and Week 16/Day 106 | Plasma concentrations of rAvPAL-PEG (BMN 165) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Starting Dose=0.001 mg/kg Subjects will start on rAvPAL-PEG 0.001 mg/kg | 7 |
| Starting Dose=0.003 mg/kg Subjects will start on rAvPAL-PEG 0.003 mg/kg | 9 |
| Starting Dose=0.01 mg/kg Subjects will start on rAvPAL-PEG 0.01 mg/kg | 13 |
| Starting Dose=0.03 mg/kg Subjects will start on rAvPAL-PEG 0.03 mg/kg | 1 |
| Starting Dose=0.1 mg/kg Subjects will start on rAvPAL-PEG 0.1 mg/kg | 10 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg |
|---|---|---|---|---|---|---|
| Age, Continuous | 26.1 years STANDARD_DEVIATION 6.35 | 23.3 years STANDARD_DEVIATION 3.45 | 29.2 years STANDARD_DEVIATION 5.95 | 26.5 years STANDARD_DEVIATION 5.65 | 22.0 years | 25.2 years STANDARD_DEVIATION 8.6 |
| Age, Customized < 18 years of age | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Customized > or = 18 years of age | 38 Participants | 7 Participants | 9 Participants | 13 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 7 Participants | 9 Participants | 13 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 38 Participants | 7 Participants | 9 Participants | 12 Participants | 1 Participants | 9 Participants |
| Region of Enrollment United States | 40 Participants | 7 Participants | 9 Participants | 13 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Female | 20 Participants | 3 Participants | 7 Participants | 6 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 20 Participants | 4 Participants | 2 Participants | 7 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 | 0 / 13 | 0 / 1 | 0 / 10 |
| other Total, other adverse events | 7 / 7 | 9 / 9 | 13 / 13 | 1 / 1 | 10 / 10 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 | 1 / 13 | 0 / 1 | 1 / 10 |
Outcome results
Primary
Blood Phenylalanine Concentrations
Time frame: Baseline, Week 1/Day 5, Week 7, Week 16/Day 106
Population: Efficacy Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Starting Dose=0.001 mg/kg | Blood Phenylalanine Concentrations | Baseline | 1382.7 umol/L | Standard Deviation 191.4 |
| Starting Dose=0.001 mg/kg | Blood Phenylalanine Concentrations | week 16 Day 106 | 1284.0 umol/L | Standard Deviation 221.73 |
| Starting Dose=0.001 mg/kg | Blood Phenylalanine Concentrations | Week 7 | 1436.0 umol/L | Standard Deviation 274.08 |
| Starting Dose=0.001 mg/kg | Blood Phenylalanine Concentrations | Week 1 Day 5 | 1405.3 umol/L | Standard Deviation 190.87 |
| Starting Dose=0.003 mg/kg | Blood Phenylalanine Concentrations | week 16 Day 106 | 1049.4 umol/L | Standard Deviation 378 |
| Starting Dose=0.003 mg/kg | Blood Phenylalanine Concentrations | Week 1 Day 5 | 1276.3 umol/L | Standard Deviation 410.22 |
| Starting Dose=0.003 mg/kg | Blood Phenylalanine Concentrations | Baseline | 1336.1 umol/L | Standard Deviation 344.87 |
| Starting Dose=0.003 mg/kg | Blood Phenylalanine Concentrations | Week 7 | 1324.8 umol/L | Standard Deviation 304.64 |
| Starting Dose=0.01 mg/kg | Blood Phenylalanine Concentrations | Week 1 Day 5 | 1216.5 umol/L | Standard Deviation 434.53 |
| Starting Dose=0.01 mg/kg | Blood Phenylalanine Concentrations | Baseline | 1290.5 umol/L | Standard Deviation 459.43 |
| Starting Dose=0.01 mg/kg | Blood Phenylalanine Concentrations | week 16 Day 106 | 1093.5 umol/L | Standard Deviation 445.02 |
| Starting Dose=0.01 mg/kg | Blood Phenylalanine Concentrations | Week 7 | 1108.7 umol/L | Standard Deviation 510.74 |
| Starting Dose=0.03 mg/kg | Blood Phenylalanine Concentrations | Week 7 | 1849.0 umol/L | — |
| Starting Dose=0.03 mg/kg | Blood Phenylalanine Concentrations | Baseline | 846.0 umol/L | — |
| Starting Dose=0.03 mg/kg | Blood Phenylalanine Concentrations | Week 1 Day 5 | 682.0 umol/L | — |
| Starting Dose =0.1 mg/kg | Blood Phenylalanine Concentrations | week 16 Day 106 | 930.7 umol/L | Standard Deviation 331.36 |
| Starting Dose =0.1 mg/kg | Blood Phenylalanine Concentrations | Baseline | 1310.3 umol/L | Standard Deviation 319.01 |
| Starting Dose =0.1 mg/kg | Blood Phenylalanine Concentrations | Week 1 Day 5 | 863.7 umol/L | Standard Deviation 307.59 |
| Starting Dose =0.1 mg/kg | Blood Phenylalanine Concentrations | Week 7 | 1321.6 umol/L | Standard Deviation 350.78 |
| Total | Blood Phenylalanine Concentrations | week 16 Day 106 | 1088.5 umol/L | Standard Deviation 367.67 |
| Total | Blood Phenylalanine Concentrations | Baseline | 1310.8 umol/L | Standard Deviation 353.86 |
| Total | Blood Phenylalanine Concentrations | Week 1 Day 5 | 1158.5 umol/L | Standard Deviation 403.63 |
| Total | Blood Phenylalanine Concentrations | Week 7 | 1284.5 umol/L | Standard Deviation 405.75 |
Secondary
Number of Participants With Positive PAL IgG Antibody
Antibody against PAL (phenylalanine ammonia lyase) measured over time
Time frame: Baseline, Week 12
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PAL IgG Antibody | Baseline | 3 Participants |
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PAL IgG Antibody | Week 12 | 7 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PAL IgG Antibody | Baseline | 2 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PAL IgG Antibody | Week 12 | 8 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PAL IgG Antibody | Baseline | 2 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PAL IgG Antibody | Week 12 | 12 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PAL IgG Antibody | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PAL IgG Antibody | Week 12 | 1 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PAL IgG Antibody | Baseline | 0 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PAL IgG Antibody | Week 12 | 10 Participants |
| Total | Number of Participants With Positive PAL IgG Antibody | Baseline | 7 Participants |
| Total | Number of Participants With Positive PAL IgG Antibody | Week 12 | 38 Participants |
Secondary
Number of Participants With Positive PAL IgM Antibody
Antibody positivity over time
Time frame: Baseline, Week 12
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PAL IgM Antibody | Baseline | 1 Participants |
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PAL IgM Antibody | Week 12 | 4 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PAL IgM Antibody | Baseline | 2 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PAL IgM Antibody | Week 12 | 3 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PAL IgM Antibody | Baseline | 5 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PAL IgM Antibody | Week 12 | 8 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PAL IgM Antibody | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PAL IgM Antibody | Week 12 | 0 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PAL IgM Antibody | Baseline | 4 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PAL IgM Antibody | Week 12 | 10 Participants |
| Total | Number of Participants With Positive PAL IgM Antibody | Baseline | 12 Participants |
| Total | Number of Participants With Positive PAL IgM Antibody | Week 12 | 25 Participants |
Secondary
Number of Participants With Positive PEG IgG Antibody
Antibody positivity over time
Time frame: Baseline, Week 16
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PEG IgG Antibody | Baseline | 2 Participants |
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PEG IgG Antibody | Week 16 | 6 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PEG IgG Antibody | Baseline | 5 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PEG IgG Antibody | Week 16 | 7 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PEG IgG Antibody | Baseline | 7 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PEG IgG Antibody | Week 16 | 12 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PEG IgG Antibody | Baseline | 1 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PEG IgG Antibody | Week 16 | 0 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PEG IgG Antibody | Baseline | 4 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PEG IgG Antibody | Week 16 | 9 Participants |
| Total | Number of Participants With Positive PEG IgG Antibody | Baseline | 19 Participants |
| Total | Number of Participants With Positive PEG IgG Antibody | Week 16 | 34 Participants |
Secondary
Number of Participants With Positive PEG IgM Antibody
Antibody positivity over time
Time frame: Baseline, Week 16
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PEG IgM Antibody | Baseline | 1 Participants |
| Starting Dose=0.001 mg/kg | Number of Participants With Positive PEG IgM Antibody | Week 16 | 7 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PEG IgM Antibody | Baseline | 2 Participants |
| Starting Dose=0.003 mg/kg | Number of Participants With Positive PEG IgM Antibody | Week 16 | 7 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PEG IgM Antibody | Baseline | 2 Participants |
| Starting Dose=0.01 mg/kg | Number of Participants With Positive PEG IgM Antibody | Week 16 | 8 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PEG IgM Antibody | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Number of Participants With Positive PEG IgM Antibody | Week 16 | 0 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PEG IgM Antibody | Baseline | 0 Participants |
| Starting Dose =0.1 mg/kg | Number of Participants With Positive PEG IgM Antibody | Week 16 | 9 Participants |
| Total | Number of Participants With Positive PEG IgM Antibody | Baseline | 5 Participants |
| Total | Number of Participants With Positive PEG IgM Antibody | Week 16 | 34 Participants |
Secondary
Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies
Antibody positivity over time
Time frame: Baseline, Week 12
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
| Total | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Baseline | 0 Participants |
| Total | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies | Week 12 | 0 Participants |
Secondary
Percentage of Participants With Positive Neutralizing Antibodies [NAb]
Antibody positivity over time
Time frame: Baseline, Week 12
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 0 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 1 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 3 Participants |
| Total | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Baseline | 0 Participants |
| Total | Percentage of Participants With Positive Neutralizing Antibodies [NAb] | Week 12 | 4 Participants |
Secondary
Percentage of Participants With Positive PAL IgE Antibody
Antibody positivity over time
Time frame: Baselline, Week 12
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Starting Dose=0.001 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 1 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Starting Dose=0.003 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Starting Dose=0.01 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 0 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Starting Dose=0.03 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Starting Dose =0.1 mg/kg | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 0 Participants |
| Total | Percentage of Participants With Positive PAL IgE Antibody | Baseline | 0 Participants |
| Total | Percentage of Participants With Positive PAL IgE Antibody | Week 12 | 1 Participants |
Secondary
Study Drug Related Adverse Events
Time frame: Screening, Weeks 1-22
Population: The safety population will consist of all subjects who receive any amount of study drug throughout the study duration and have post-treatment safety information (laboratory values, vital signs, adverse events, 12-lead electrocardiogram, antibodies, and physical examinations).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Starting Dose=0.001 mg/kg | Study Drug Related Adverse Events | 5 Participants |
| Starting Dose=0.003 mg/kg | Study Drug Related Adverse Events | 9 Participants |
| Starting Dose=0.01 mg/kg | Study Drug Related Adverse Events | 11 Participants |
| Starting Dose=0.03 mg/kg | Study Drug Related Adverse Events | 1 Participants |
| Starting Dose =0.1 mg/kg | Study Drug Related Adverse Events | 10 Participants |
| Total | Study Drug Related Adverse Events | 36 Participants |
Other Pre-specified
Trough Concentration of BMN 165
Plasma concentrations of rAvPAL-PEG (BMN 165)
Time frame: Baseline, Baseline/pre-dose, Week 7, and Week 16/Day 106
Population: The PK population will consist of all subjects who received any amount of study drug and have post-treatment plasma BMN 165 concentration measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Starting Dose=0.001 mg/kg | Trough Concentration of BMN 165 | Baseline | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.001 mg/kg | Trough Concentration of BMN 165 | Week 16-Day 106 | 7.8 ng/mL | Standard Deviation 20.52 |
| Starting Dose=0.001 mg/kg | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.003 mg/kg | Trough Concentration of BMN 165 | Week 16-Day 106 | 3.1 ng/mL | Standard Deviation 8.7 |
| Starting Dose=0.003 mg/kg | Trough Concentration of BMN 165 | Baseline | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.003 mg/kg | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.01 mg/kg | Trough Concentration of BMN 165 | Baseline | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.01 mg/kg | Trough Concentration of BMN 165 | Week 16-Day 106 | 6.0 ng/mL | Standard Deviation 14.54 |
| Starting Dose=0.01 mg/kg | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | Standard Deviation 0 |
| Starting Dose=0.03 mg/kg | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | — |
| Starting Dose=0.03 mg/kg | Trough Concentration of BMN 165 | Baseline | 0 ng/mL | — |
| Starting Dose =0.1 mg/kg | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | Standard Deviation 0 |
| Starting Dose =0.1 mg/kg | Trough Concentration of BMN 165 | Baseline, pre-dose | 1.6 ng/mL | Standard Deviation 5.06 |
| Starting Dose =0.1 mg/kg | Trough Concentration of BMN 165 | Week 16-Day 106 | 0 ng/mL | Standard Deviation 0 |
| Total | Trough Concentration of BMN 165 | Baseline | 0 ng/mL | Standard Deviation 0 |
| Total | Trough Concentration of BMN 165 | Baseline, pre-dose | 1.6 ng/mL | Standard Deviation 5.06 |
| Total | Trough Concentration of BMN 165 | Week 16-Day 106 | 4.2 ng/mL | Standard Deviation 12.74 |
| Total | Trough Concentration of BMN 165 | Week 7 | 0 ng/mL | Standard Deviation 0 |