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PhenylketonuriaPhase 2NCT01212744

Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU)

A Phase 2 study testing rAvPAL-PEG in people with Phenylketonuria, run by BioMarin Pharmaceutical at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effect of daily administration of rAvPAL-PEG on the reduction of blood Phe concentrations in subjects with PKU. Read more about this study

Who is it for?
Ages 16 to 70 years
Conditions the study is for
Phenylketonuria
What is being tested?
rAvPAL-PEG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
9 sitesUnited States
Study dates
Mar 2011to Apr 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis of PKU with both of the following: current blood Phe concentration of ≥ 600 micromol/L at screening and average blood Phe concentration of ≥ 600 micromol/L over the past 3 years, using available data
  • 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 ≥ 4 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 legally authorized representative, after the nature of the study has been explained, and prior to any research-related procedures.
  • Willing and able to comply with all study procedures.
  • Between the ages of 16 and 70 years, inclusive.
  • Negative pregnancy test at screening and willing to have additional pregnancy tests performed during the study for females of childbearing potential only. Females considered not of childbearing potential are those who have been in menopause for at least 2 years or have had a tubal ligation at least 1 year prior to screening, or who have had a total hysterectomy.
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  • Willing to use an acceptable method of contraception while participating in the study (sexually active subjects only).
  • 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 ECG at screening.

Who cannot join

  • Prior use of rAvPAL-PEG.
  • Use of any investigational product 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.
  • Known hypersensitivity to rAvPAL-PEG excipients.
  • Breastfeeding at screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
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  • 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 investigator, 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Albany Medical Center

    Albany, New York, 12208

  • The Children's Hospital

    Aurora, Colorado, 80045

  • University of Missouri

    Columbia, Missouri, 65212

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Florida

    Gainesville, Florida, 32610

  • Weisskopf Child Evaluation Center / University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin-Madison

    Madison, Wisconsin, 53705

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Washington University Center for Applied Research Sciences

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 2, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Dose Levels of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria

The purpose of this study is to evaluate the effect of daily administration of rAvPAL-PEG on the reduction of blood Phe concentrations in subjects with PKU.

Read the detailed description

This 16-week multi-center, open-label, Phase 2 study is designed to evaluate the safety, tolerability,and efficacy of daily SC injections of rAvPAL-PEG in subjects with PKU. Subjects who are naïve to prior treatment with rAvPAL-PEG and who have met the other study eligibility criteria will be enrolled at approximately 8 sites in the US and Canada. Up to 6 daily dose levels of rAvPAL-PEG are planned and may be assessed during this study (0.06 mg/kg/day, 0.1 mg/kg/day, 0.2 mg/kg/day;0.4 mg/kg/day, 0.6 mg/kg/day, or 0.8 mg/kg/day). Enrollment will begin with the 0.4 mg/kg/day dose level and additional higher or lower doses may be added. The additional dose levels chosen for assessment will be based on the safety (systemic reaction or clinically significant abnormal laboratory test results assessed as related to study drug) and efficacy (blood Phe reduction to less than or equal to 60 μmol/L) information of at least 3 subjects with at least 2 weeks of daily dosing with rAvPAL-PEG. Initiation of dosing at higher or lower dose levels will be per the determination of the Sponsor's Medical Officer in consultation with the Investigator.

Conditions
Phenylketonuria
Being tested
rAvPAL-PEG
Keywords
PEG PAL; PKU; injection;
Medical subject headings
Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rAvPAL-PEGDrug

    Also called Recombinant Anabaena variabilis phenylalanine ammonia lyase

    0.06 mg/kg/day, 0.1 mg/kg/day, 0.2 mg/kg/day, 0.4 mg/kg/day, 0.6 mg/kg/day, 0.8 mg/kg/day

Study groups in NCT01212744
Study groupRoleWhat they receive
rAvPAL-PEGExperimentalrAvPAL-PEG in varying doses
Receives: Drug: rAvPAL-PEG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Blood Phenylalanine Concentration

    Plasma Phe

    Measured: Baseline, Week 16

Secondary outcomes (9)

  1. Study Drug Related Adverse Events

    Safety will be evaluated on the incidence of AEs and clinically significant changes in vital signs as well as clinical labs and ECG. Please refer to AE section below for comprehensive listing of all adverse events recorded during study.

    Measured: Weekly

  2. Percentage of Participants With PAL IgG Antibody Percentage of Participants With Positive PAL IgG

    Antibody against phenylalanine ammonia lyase (PAL)

    Measured: Baseline, Week 16

  3. Plasma Concentrations of rAvPAL-PEG (BMN 165)

    Measurements taken pre-dose

    Measured: Baseline, Week 8, Week 13

  4. Percentage of Participants With PEG-IgG Antibody Positivity

    Antibodies against polyethylene glycol (PEG) of the IgG isotype

    Measured: Baseline, Week 16

  5. Percentage of Participants With PAL-IgM Antibody Positivity

    Antibodies against phenylalanine ammonia lyase (PAL) of the IgM isotype

    Measured: Baseline, Week 16

  6. Percentage of Participants With PEG-IgM Antibody Positivity

    Antibodies against polyethylene glycol (PEG) of the IgM isotype

    Measured: Baseline, Week 16

  7. Percentage of Participants With Neutralizing Antibody Positivity

    Antibody positivity over time

    Measured: Baseline, Week 16

  8. Percentage of Participants With PAL-IgE Antibody Positivity

    Antibodies against phenylalanine ammonia lyase (PAL) of the IgE isotype

    Measured: Baseline, Week 16

  9. Percentage of Participants With PAL-PEG-IgE Antibody Positivity

    Antibodies against phenylalanine ammonia lyase (PAL)-polyethylene glycol (PEG) of the IgE isotype

    Measured: Baseline, Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2010 (estimated)
  2. Study startMar 2011
  3. Primary completionApr 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01212744
Sponsor's protocol ID
PAL-004
Status last verified
Feb 2019
First submitted
29 Sep 2010
Last updated
26 Feb 2019
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Burton BK, Longo N, Vockley J, Grange DK, Harding CO, Decker C, Li M, Lau K, Rosen O, Larimore K, Thomas J; PAL-002 and PAL-004 Investigators. Pegvaliase for the treatment of phenylketonuria: Results of the phase 2 dose-finding studies with long-term follow-up. Mol Genet Metab. 2020 Aug;130(4):239-246. doi: 10.1016/j.ymgme.2020.06.006. Epub 2020 Jun 16.

    PubMed 32593547

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rAvPAL-PEG in people with Phenylketonuria, run by BioMarin Pharmaceutical at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Blood Phenylalanine Concentration (time frame: Baseline, Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01212744, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2019.

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