PhenylketonuriaPhase 3Prism301NCT01819727
An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
A Phase 3 study testing BMN 165 in people with Phenylketonuria, run by BioMarin Pharmaceutical at 31 sites in United States.
Trial summary
The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in patients 18 to 70 years old with hyperphenylalaninemia due to PKU. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- BMN 165
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 261 participants
- Where
- 31 sitesUnited States
- Study dates
- May 2013to 25 Nov 2015
- Phase
- Phase 3
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals eligible to participate in this study must meet all of the following criteria:
- A current diagnosis of PKU with the following:
- Current blood Phe concentration >600 µmol/L at screening and
- Average blood Phe concentration of >600 µmol/L over the past 6 months (per available data)
- Have no previous exposure to BMN 165
- Are ≥18 and ≤70 years of age at the time of screening
Show all 21Show fewer
- Subjects who are < 18 years of age but are already enrolled into the study may continue to participate
- If taking Kuvan, have a treatment end date ≥14 days prior to Day 1 (ie, first dose of BMN 165)
- Are 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
- Are willing and able to comply with all study procedures
- Has identified a person who is ≥ 18 years of age who has the neurocognitive and linguistic capacities to comprehend and complete the POMS-Observer-rated scale
- Has identified a competent person or persons who are ≥ 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration until dose titration has completed and if needed upon return to dosing after an AE and per investigator determination.
- A home healthcare nurse may perform the study drug observations.
- For females of childbearing potential, must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. (Females are considered not of childbearing potential if they have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to screening, or have had a total hysterectomy.)
- If sexually active, must be willing to use 2 acceptable methods of contraception while participating in the study and 4 weeks after the study.
- Males post vasectomy 2 years with no known pregnancies for at least 2 years do not need to use any other forms of birth control during the study.
- Females who have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to screening, or have had a total hysterectomy do not need to use any other forms of contraception during the study.
- Have received documented approval from a study dietician confirming that the subject is capable of maintaining their diet in accordance with dietary information presented in the protocol.
- Have neurocognitive and linguistic capacities to comprehend and answer investigator's prompts for the ADHD RS- Investigator rated instrument and to complete the POMS-Subject rated scale.
- If applicable, maintained stable dose of medication for attention deficit hyperactivity disorder (ADHD), depression, anxiety, or other psychiatric disorder for ≥8 weeks prior to enrollment and willing to maintain stable dose throughout study unless a change is medically indicated.
- Are in generally good health, as evidenced by physical examination, clinical laboratory evaluations and ECG tests performed at screening
Who cannot join
- Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
- 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 (except Kuvan), including the use of large neutral amino acids, within 2 days prior to administration of study drug Day 1 (first dose of BMN 165). Note: Kuvan treatment must be stopped ≥14 days before Day 1
- Use or planned use of any injectable drugs containing PEG (other than BMN 165), including medroxyprogesterone injection, within 3 months prior to screening and during study participation
- Known hypersensitivity to any components of BMN 165
- Current use of levodopa
Show all 16Show fewer
- A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody
- A history of organ transplantation or on chronic immunosuppressive therapy
- A history of substance abuse (as defined by the Diagnostic and Statistical Manual of Mental Disorders [DSM IV]) in the past 12 months or current alcohol or drug abuse
- Current participation in the Kuvan registry study (PKU Demographics, Outcomes and Safety [PKUDOS]). Patients may discontinue the PKUDOS registry trial to allow enrollment in this study
- Pregnant or breastfeeding at screening or planning to become pregnant (self or partner) or 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)
- Major surgery planned during the study period
- Any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or terminating early from 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
31 sites in 1 country.
31 sites in 1 country
United States31 sites
Albany Medical College
Albany, New York, 12208
The Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Cooper Health Systems
Camden, New Jersey, 08103
Ann and Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospital Cleveland, Case Medical Center
Cleveland, Ohio, 44106
University of Missouri
Columbia, Missouri, 65212
Emory Universty
Decatur, Georgia, 30033
Wayne State University
Detroit, Michigan, 48201
University of Florida Clinical Research Center
Gainesville, Florida, 32610
University of Texas Health Science at Houston
Houston, Texas, 77030
Riley Children's Hospital
Indianapolis, Indiana, 46202
University of California, Altman Clinical and Translational Research Institute
La Jolla, California, 92037
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Weisskopf Child Evaluation Center / University of Louisville
Louisville, Kentucky, 40202
University of Miami Health System
Miami, Florida, 33136
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Atlantic Health System - Morristown Medical Center
Morristown, New Jersey, 07960
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Icahn School of Medicine at Mount Sinai Medical Center
New York, New York, 10029
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University
Portland, Oregon, 97239
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84132
University of Washington Medical Center
Seattle, Washington, 98195
Washington University Center for Applied Research Sciences
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33606
About this study
Official title: A Phase 3, Open-Label, Randomized, Multi-Center Study to Assess the Safety & Tolerability of an Induction, Titration, and Maintenance Dose Regimen of BMN 165 Self Administered by Adults With PKU Not Previously Treated With BMN 165
The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in patients 18 to 70 years old with hyperphenylalaninemia due to PKU. Study BMN 165-301 is a Phase 3, open-label, randomized study designed to further characterize the safety of BMN 165 during two induction, titration, and maintenance dose regimens in adults with PKU who have not had previous exposure to BMN 165 (naive). Subjects will be randomized (1:1) to titrate up to one of two dose regimens. Other key features of this study are the dose regimens chosen for induction and titration; the study duration; self administration of study drug; and the chosen tertiary objectives.
Read the detailed description
Primary and Secondary Outcomes:
The primary objective of the study is the following:
- To characterize the safety and tolerability during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day
The secondary objective of the study is the following:
- To evaluate blood Phe concentration during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day
The tertiary objectives of the study are the following:
- Percentage of daily recommended intake for age of natural protein intake
- Dietary protein intake from medical food and intact food
- The ADHD-RS score (-Investigator Rated; inattentive subscale score, total score, and hyperactivity/impulsivity subscale score)
- POMS scores (-Observer Rated and -Subject Rated)
- Trough plasma concentrations of BMN 165
Primary Analysis:
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of AEs will be summarized by system organ class, preferred term, relationship to study drug, and severity for the subjects who are randomized to the 40 mg/day dose, the 20 mg/day dose, and overall. A by-subject listing will be provided for those subjects who experience an SAE, including death, or experience an AE associated with early withdrawal from the study or study drug. Hypersensitivity AEs and AEs that result in dosing interruption or dose reduction are of interest, and the percentage of subjects who report these AEs will be presented.
Clinical laboratory data will be summarized by the type of laboratory test for the subjects who are randomized to the 40 mg/day dose, the 20 mg /day dose, and overall. Frequency and percentage of subjects who experience abnormal (ie, outside of reference range) and/or clinically significant abnormalities after study drug administration will be presented for each clinical laboratory test. For each clinical laboratory test, descriptive statistics will be provided for baseline and all subsequent post-baseline visits. Changes from baseline to the post-baseline visits will also be provided. Descriptive statistics, including clinically significant changes from baseline, of vital signs, physical examination results, ECG test results, and immunogenicity test results will also be provided in a similar manner. Additionally, antibodies and titers will be summarized at the scheduled time point.
Detailed statistical methods will be provided in the Statistical Analysis Plan (SAP).
Secondary Analysis:
The secondary efficacy endpoint is change from baseline to end of study in blood Phe concentration.
Baseline is defined as the average of blood Phe concentrations collected prior to dosing at the Screening Visit and on Day 1.
The primary analysis method for the secondary endpoint will use a repeated measures model, with change from baseline Phe as the dependent variable and dose (40 mg/day or 20 mg/day), study week, and baseline Phe as independent variables.
A responder analysis will be presented as a cumulative distribution function. The percentage of subjects with blood Phe concentration below "X" umol/L at the end of the study will be plotted and summarized for various "X" as a cumulative distribution function for each of the 2 doses and overall.
Detailed statistical methods will be provided in the SAP.
Tertiary Analyses:
The statistical analysis method for tertiary endpoints (protein intake; the ADHD-RS IV score) will be descriptive. More details regarding the analysis methods for the tertiary endpoints will be provided in the SAP.
Trough plasma concentrations of BMN 165 will be evaluated.
DMC The Data Monitoring Committee (DMC) will act in an advisory capacity to
BioMarin to monitor subject safety and the efficacy of BMN 165 in subjects who participate in Study BMN 165-301 .The DMC responsibilities may include the following:
- Review the study protocol, informed consent and assent documents, and plans for data monitoring
- Evaluate the progress of the trial; study data quality; timeliness; subject recruitment, accrual and retention; subjects' risk versus benefit; and other factors that could affect the study outcome
- Consider relevant information that may have an effect on the safety of the participants or the ethics of the study
- Protect the safety of the study participants in accordance with the stopping rules as defined in study protocol
- Make recommendations to BioMarin concerning continuation or termination of the study or other modifications of the study based on their observations
- If appropriate, conduct interim analysis of safety and efficacy
- Conditions
- Phenylketonuria
- Being tested
- BMN 165
- Keywords
- PKU, PEG-PAL, BioMarin, rAv-PAL PEG, BMN 165, open label, Prism301, Pegvaliase
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMN 165Drug
Also called rAvPAL-PEG, Pegvaliase
After informed consent, eligible subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day. All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the Induction Period, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly BMN 165 dose to a daily dose regimen of 20 mg/day or 40 mg/day. The Titration Period will be individualized to each subject based on a minimum of 6 weeks (the amount of time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 30 weeks (accounts for dose reduction or interruption due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose regimen. The majority of subjects will maintain the 20 or 40 mg/day dose regimen for at least an additional 2 weeks until a minimum of approximately 26 weeks or a maximum of 36 weeks in the study.
| Study group | Role | What they receive |
|---|---|---|
| BMN 165, 20mg/day | Active comparator | Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L). Receives: Drug: BMN 165 |
| BMN 165, 40mg/day | Active comparator | Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L). Receives: Drug: BMN 165 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Hypersensitivity Adverse Reaction
Hypersensitivity AEs will be identified in two ways:
- Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ)
- Modified Hypersensitivity SMQ to include above additional preferred terms
Measured: baseline and 36 weeks
Secondary outcomes (1)
Blood Phenylalanine Concentration
Plasma phenylalanine (Phe) concentration
Measured: baseline and 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2013 (estimated)
- Study startMay 2013
- Primary completion25 Nov 2015
- Study completion25 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 261 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Markus Merilainen, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01819727
- Sponsor's protocol ID
- 165-301
- Other IDs
- Prism301
- Acronym
- Prism301
- Status last verified
- Feb 2019
- First submitted
- 18 Mar 2013
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Harding CO, Whitehall KB, Lilienstein J, Sazova O, Lindstrom K, Levy DG, Burton BK. Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase-3 PRISM open-label extension study. Genet Med. 2025 Aug;27(8):101459. doi: 10.1016/j.gim.2025.101459. Epub 2025 May 20.
PubMed 40411344Bilder DA, Arnold GL, Dimmock D, Grant ML, Janzen D, Longo N, Nguyen-Driver M, Jurecki E, Merilainen M, Amato G, Waisbren S. Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria. Am J Med Genet A. 2022 Mar;188(3):768-778. doi: 10.1002/ajmg.a.62574. Epub 2021 Nov 26.
PubMed 34826353
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-Label, Randomized, Multi-Center Study to Assess the Safety & Tolerability of an Induction, Titration, and Maintenance Dose Regimen of BMN 165 Self Administered by Adults With PKU Not Previously Treated With BMN 165
- ClinicalTrials.gov ID
- NCT01819727
- Acronym / sponsor ID
- Prism301 / 165-301
- Conditions
- Phenylketonuria
- Keywords
- PKU, PEG-PAL, BioMarin, rAv-PAL PEG, BMN 165, open label, Prism301, Pegvaliase
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 261 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- 25 Nov 2015 (actual)
- Study completion
- 25 Nov 2015 (actual)
- First posted
- 28 Mar 2013 (estimated)
- Results
- Posted 10 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in patients 18 to 70 years old with hyperphenylalaninemia due to PKU. Study BMN 165-301 is a Phase 3, open-label, randomized study designed to further characterize the safety of BMN 165 during two induction, titration, and maintenance dose regimens in adults with PKU who have not had previous exposure to BMN 165 (naive). Subjects will be randomized (1:1) to titrate up to one of two dose regimens. Other key features of this study are the dose regimens chosen for induction and titration; the study duration; self administration of study drug; and the chosen tertiary objectives.
Detailed description
Primary and Secondary Outcomes:
The primary objective of the study is the following:
- To characterize the safety and tolerability during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day
The secondary objective of the study is the following:
- To evaluate blood Phe concentration during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day
The tertiary objectives of the study are the following:
- Percentage of daily recommended intake for age of natural protein intake
- Dietary protein intake from medical food and intact food
- The ADHD-RS score (-Investigator Rated; inattentive subscale score, total score, and hyperactivity/impulsivity subscale score)
- POMS scores (-Observer Rated and -Subject Rated)
- Trough plasma concentrations of BMN 165
Primary Analysis:
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of AEs will be summarized by system organ class, preferred term, relationship to study drug, and severity for the subjects who are randomized to the 40 mg/day dose, the 20 mg/day dose, and overall. A by-subject listing will be provided for those subjects who experience an SAE, including death, or experience an AE associated with early withdrawal from the study or study drug. Hypersensitivity AEs and AEs that result in dosing interruption or dose reduction are of interest, and the percentage of subjects who report these AEs will be presented.
Clinical laboratory data will be summarized by the type of laboratory test for the subjects who are randomized to the 40 mg/day dose, the 20 mg /day dose, and overall. Frequency and percentage of subjects who experience abnormal (ie, outside of reference range) and/or clinically significant abnormalities after study drug administration will be presented for each clinical laboratory test. For each clinical laboratory test, descriptive statistics will be provided for baseline and all subsequent post-baseline visits. Changes from baseline to the post-baseline visits will also be provided. Descriptive statistics, including clinically significant changes from baseline, of vital signs, physical examination results, ECG test results, and immunogenicity test results will also be provided in a similar manner. Additionally, antibodies and titers will be summarized at the scheduled time point.
Detailed statistical methods will be provided in the Statistical Analysis Plan (SAP).
Secondary Analysis:
The secondary efficacy endpoint is change from baseline to end of study in blood Phe concentration.
Baseline is defined as the average of blood Phe concentrations collected prior to dosing at the Screening Visit and on Day 1.
The primary analysis method for the secondary endpoint will use a repeated measures model, with change from baseline Phe as the dependent variable and dose (40 mg/day or 20 mg/day), study week, and baseline Phe as independent variables.
A responder analysis will be presented as a cumulative distribution function. The percentage of subjects with blood Phe concentration below "X" umol/L at the end of the study will be plotted and summarized for various "X" as a cumulative distribution function for each of the 2 doses and overall.
Detailed statistical methods will be provided in the SAP.
Tertiary Analyses:
The statistical analysis method for tertiary endpoints (protein intake; the ADHD-RS IV score) will be descriptive. More details regarding the analysis methods for the tertiary endpoints will be provided in the SAP.
Trough plasma concentrations of BMN 165 will be evaluated.
DMC The Data Monitoring Committee (DMC) will act in an advisory capacity to
BioMarin to monitor subject safety and the efficacy of BMN 165 in subjects who participate in Study BMN 165-301 .The DMC responsibilities may include the following:
- Review the study protocol, informed consent and assent documents, and plans for data monitoring
- Evaluate the progress of the trial; study data quality; timeliness; subject recruitment, accrual and retention; subjects' risk versus benefit; and other factors that could affect the study outcome
- Consider relevant information that may have an effect on the safety of the participants or the ethics of the study
- Protect the safety of the study participants in accordance with the stopping rules as defined in study protocol
- Make recommendations to BioMarin concerning continuation or termination of the study or other modifications of the study based on their observations
- If appropriate, conduct interim analysis of safety and efficacy
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BMN 165, 20mg/day | Active comparator | Drug: BMN 165Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L). |
| BMN 165, 40mg/day | Active comparator | Drug: BMN 165Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Individuals eligible to participate in this study must meet all of the following criteria:
- A current diagnosis of PKU with the following:
- Have no previous exposure to BMN 165
- Are ≥18 and ≤70 years of age at the time of screening
- If taking Kuvan, have a treatment end date ≥14 days prior to Day 1 (ie, first dose of BMN 165)
Key exclusion criteria (16 listed)
- Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
- 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 (except Kuvan), including the use of large neutral amino acids, within 2 days prior to administration of study drug Day 1 (first dose of BMN 165). Note: Kuvan treatment must be stopped ≥14 days before Day 1
- Use or planned use of any injectable drugs containing PEG (other than BMN 165), including medroxyprogesterone injection, within 3 months prior to screening and during study participation
- Known hypersensitivity to any components of BMN 165
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMN 165Also: rAvPAL-PEG, PegvaliaseAfter informed consent, eligible subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day. All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the Induction Period, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly BMN 165 dose to a daily dose regimen of 20 mg/day or 40 mg/day. The Titration Period will be individualized to each subject based on a minimum of 6 weeks (the amount of time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 30 weeks (accounts for dose reduction or interruption due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose regimen. The majority of subjects will maintain the 20 or 40 mg/day dose regimen for at least an additional 2 weeks until a minimum of approximately 26 weeks or a maximum of 36 weeks in the study. | Drug | BMN 165, 20mg/day, BMN 165, 40mg/day |
Primary outcome
Number of Participants With Hypersensitivity Adverse Reaction
Time frame: baseline and 36 weeks
Hypersensitivity AEs will be identified in two ways: * Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ) * Modified Hypersensitivity SMQ to include above additional preferred terms
1 secondary outcome
Blood Phenylalanine Concentration
Time frame: baseline and 36 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40411344Harding CO, Whitehall KB, Lilienstein J, Sazova O, Lindstrom K, Levy DG, Burton BK. Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase-3 PRISM open-label extension study. Genet Med. 2025 Aug;27(8):101459. doi: 10.1016/j.gim.2025.101459. Epub 2025 May 20.
- Derived from this study: PubMed 34826353Bilder DA, Arnold GL, Dimmock D, Grant ML, Janzen D, Longo N, Nguyen-Driver M, Jurecki E, Merilainen M, Amato G, Waisbren S. Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria. Am J Med Genet A. 2022 Mar;188(3):768-778. doi: 10.1002/ajmg.a.62574. Epub 2021 Nov 26.
- Biomarin Pharmaceutical websiteLink provided by the sponsor.
- BioMarin sponsored PKU educational/community websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Phenylketonuria
RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Merilainen, MD study director
BioMarin Pharmaceutical
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BMN 165 in people with Phenylketonuria, run by BioMarin Pharmaceutical at 31 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 21 inclusion and 16 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 31 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 Sep 2018). 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?
Number of Participants With Hypersensitivity Adverse Reaction (time frame: baseline and 36 weeks). 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 NCT01819727, which also lists 2 linked publications.
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.