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PhenylketonuriaPhase 2NCT01560286

A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks

A Phase 2 study testing BMN 165 (rAvPAL-PEG) in people with Phenylketonuria, run by BioMarin Pharmaceutical at 6 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 primary objective of the study is to evaluate the effect of dosing regimens of multiple subcutaneous (SC) doses of rAvPAL-PEG to induce an early and sustained Phe reduction while decreasing the frequency and severity of hypersensitivity reactions in patients 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?
BMN 165 (rAvPAL-PEG)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
6 sitesUnited States
Study dates
May 2012to Jul 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

  • A diagnosis of PKU, with the following:
  • Current blood Phe concentration of ≥ 600 µmol/L at Screening.
  • Average blood Phe concentration of ≥ 600 µmol/L over the past 6 months, using available data.
  • Naïve to prior treatment with rAvPAL-PEG.
  • Evidence that the patient is a non responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan, insufficient response per investigator determination, unsuitable for Kuvan® per Investigator determination, and treatment end date ≥ 2 days prior to Day 1 [ie, first dose]). Patients 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 after the nature of the study has been explained and prior to any research-related procedures. In the case of participants under the age of 18 or participants who have been deemed mentally unable to provide informed consent, a parent or legal guardian may provide written informed consent (and, if required, the patient will provide written assent).
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  • Willing and able to comply with all study procedures.
  • Between the ages of 16 and 70 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 patients 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 and willing to continue with the diet while on study so as to avoid potential variability of response due to variations in dietary intake.
  • In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.

Who cannot join

  • 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, including use of large amino acids, within 2 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 a PEG containing product. Patients 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).
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  • Any condition that, in the view of the PI, places the patient 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.
  • A positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen and hepatitis C antibody.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Albany Medical Center

    Albany, New York, 12208

  • The Children's Hospital

    Aurora, Colorado, 80048

  • Children's Hospital Boston

    Boston, Massachusetts, 02115

  • University of Florida, Gainesville

    Gainesville, Florida, 32610

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

Other trials in United States

About this study

Official title: A Phase II, Multi-center, Open-label, Dose-finding Study to Evaluate Safety, Efficacy and Tolerability of Subcutaneously (SC) Administered rAvPAL-PEG in Patients With PKU for 24 Weeks

The primary objective of the study is to evaluate the effect of dosing regimens of multiple subcutaneous (SC) doses of rAvPAL-PEG to induce an early and sustained Phe reduction while decreasing the frequency and severity of hypersensitivity reactions in patients with PKU.

Read the detailed description

The primary rationale for this study is to define an optimal rAvPAL-PEG dose regimen by establishing the therapeutic effect within the shortest time possible time for induction, titration and maintenance phases while reducing the severity and frequency of hypersensitivity reactions that may lead to dose interruptions. It is hypothesized that these goals can be achieved by keeping rAvPAL-PEG doses low when anti-PEG IgM response is predicted to be high and titrating to an efficacious dose once the IgG response to PAL has developed. Further investigation is needed to determine how early and quickly patients can titrate safely to lower blood Phe; therefore, this protocol proposes to assess two Groups using an induction/titration and maintenance schedule with an aim towards establishing the therapeutic effect safety within an optimal period of time.

Conditions
Phenylketonuria
Being tested
BMN 165 (rAvPAL-PEG)
Keywords
PKU, Injections, PEG-PAL, PAL
Medical subject headings
Phenylketonurias

What participants receive

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

  • BMN 165 (rAvPAL-PEG)Biological

    Also called Recombinant Anabaena variabilis phenylalanine ammonia lyase

    Subcutaneous injection of rAvPAL-PEG administered from 1 time up to 5 times per week between 2.5mg up to a maximum of 375mg for 24 weeks.

Study groups in NCT01560286
Study groupRoleWhat they receive
Group 1Experimental4-8 week induction of rAvPAL-PEG at 2.5 mg, followed by titration to maintenance dose
Receives: Biological: BMN 165 (rAvPAL-PEG)

What is being measured

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

  1. Blood Phenylalanine Concentration

    All patients will have their plasma Phenylalanine (Phe) assessed. Please note that "Pharmacokinetics Sub-study" was not performed, and thus no results are available.

    Measured: Baseline, Week 24

Secondary outcomes (9)

  1. Number of Participants With Study Drug Related Adverse Events

    Measured: Minimum Weekly Assessment of Injection Sites, Vital Signs and Adverse Events. Other Safety Assessments will be performed at other intervals (below):

  2. Percentage of Participants With Positive Anti-PAL Immunoglobulin G [IgG]

    Antibody Positivity

    Measured: Baseline, Week 24

  3. Trough Concentration of BMN 165

    PK assessment from pre-dose blood draw.

    Measured: Week 1, Week 24

  4. Percentage of Participants With Positive Anti-PEG IgG

    Antibody Positivity

    Measured: Baseline, Week 24

  5. Percentage of Participants With Positive PAL-IgM

    Antibody Positivity

    Measured: Baseline, Week 24

  6. Percentage of Participants With Positive Anti-PEG-IgM

    Antibody positivity

    Measured: Baseline, Week 24

  7. Percentage of Participants With Positive Neutralizing Antibodies [Nab]

    Antibody positivity

    Measured: Baseline, Week 24

  8. Percentage of Participants With Positive Anti-PAL-IgE Antibodies

    Antibody positivity

    Measured: Baseline, Week 24

  9. Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies

    Antibody positivity

    Measured: Baseline, Week 24

Timeline

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

  1. First posted22 Mar 2012 (estimated)
  2. Study startMay 2012
  3. Primary completionSep 2013
  4. Study completionJul 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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01560286
Sponsor's protocol ID
165-205
Status last verified
Jul 2019
First submitted
5 Mar 2012
Last updated
6 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BMN 165 (rAvPAL-PEG) in people with Phenylketonuria, run by BioMarin Pharmaceutical at 6 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 12 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 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 27 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 24). 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 NCT01560286.

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 6 Aug 2019.

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