Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00925054
• Date of registration: 17/06/2009
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical
• Public title: Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU
• Scientific 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
• Date of first enrolment: September 2009
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00925054
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Ari Gershman, MD
• Affiliation: BioMarin Pharmaceutical

Key inclusion & exclusion criteria

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.



Age minimum: 16 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Drug: rAvPAL-PEG 0.1 mg/kg

Drug: rAvPAL-PEG 0.001 mg/kg

Drug: rAvPAL-PEG 0.003 mg/kg

Drug: rAvPAL-PEG 0.03 mg/kg

Drug: rAvPAL-PEG 0.01 mg/kg

Primary Outcome(s)

Blood Phenylalanine Concentrations [Time Frame: Baseline, Week 1/Day 5, Week 7, Week 16/Day 106]

Secondary Outcome(s)

Number of Participants With Positive PAL IgM Antibody [Time Frame: Baseline, Week 12]

Number of Participants With Positive PEG IgG Antibody [Time Frame: Baseline, Week 16]

Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies [Time Frame: Baseline, Week 12]

Percentage of Participants With Positive PAL IgE Antibody [Time Frame: Baselline, Week 12]

Percentage of Participants With Positive Neutralizing Antibodies [NAb] [Time Frame: Baseline, Week 12]

Study Drug Related Adverse Events [Time Frame: Screening, Weeks 1-22]

Number of Participants With Positive PAL IgG Antibody [Time Frame: Baseline, Week 12]

Number of Participants With Positive PEG IgM Antibody [Time Frame: Baseline, Week 16]

Secondary ID(s)

PAL-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00925054