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A Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Subcutaneous Injections of BMN 165 in PKU Adults Who Have Previously Been Exposed to BMN165 (Prism302)

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
BioMarin Pharmaceutical Identifier:
First received: June 18, 2013
Last updated: June 10, 2014
Last verified: June 2014

The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in adults with PKU.

Condition Intervention Phase
Phenylketonuria (PKU)
Drug: BMN165 20mg/day
Drug: BMN165 40mg/day
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Three-Part, Phase 3, Randomized, Double-Blind, Placebo-Controlled, Four-Arm, Discontinuation Study to Evaluate the Efficacy and Safety of Subcutaneous Injections of BMN 165 Self Administered by Adults With Phenylketonuria

Resource links provided by NLM:

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Incidence of adverse events experienced by subjects. [ Time Frame: Weekly throughout study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    Subjects will be assessed weekly for adverse events, including laboratory abnormalities.

  • Plasma phenylalanine level at Part 2 Week 8 in subjects on placebo versus BMN 165. [ Time Frame: Part 2 Week 8 ] [ Designated as safety issue: No ]
    All subjects will have plasma phenylalanine level assessed at Part 2 Week 8. The comparison will be between subjects on placebo versus subjects on study drug (BMN 165).

Secondary Outcome Measures:
  • Cognitive and mood symptoms at Part 2 Week 8 in subjects on placebo versus BMN 165 [ Time Frame: Part 2 Week 8 ] [ Designated as safety issue: No ]
    ADHD-RS IV and the POMS (Profile of Mood States) will be used to evaluate cognitive and mood symptoms in subjects who self administer BMN 165 (40 or 20 mg/day) compared with subjects who self administer a placebo.

Other Outcome Measures:
  • Protein intake as reported by subjects in diet diary [ Time Frame: Every 4 weeks, an expected average of 3 years ] [ Designated as safety issue: No ]
    Diet diary collected monthly to assess protein intake from medical food and from natural protein. This will evaluate patient compliance to study requirements.

  • Trough plasma concentration (Cmin) of BMN 165 [ Time Frame: Part 2 Week 1, 4 and 8 ] [ Designated as safety issue: No ]
    Trough plasma concentrations of BMN 165 in subjects during Part 2 of the study assessed via pre-dose PK blood draw.

  • Plasma phenylalanine level in Part 3 (long term extension) [ Time Frame: Every 4 weeks, up to 172 weeks ] [ Designated as safety issue: No ]
    Pre-dose plasma sample drawn to assess the long-term effect of BMN 165 (40 mg/day) on blood Phe concentration.

  • Cognitive and mood symptoms in Part 3 (long term extension) [ Time Frame: Every 24 weeks, up to 172 weeks ] [ Designated as safety issue: No ]
    Cognitive and mood symptoms at Part 2 Week 8 in subjects on placebo versus BMN 165 ADHD-RS IV and the POMS (Profile of Mood States) will be used to evaluate cognitive and mood symptoms in subjects during the long-term extension.

  • Plasma concentration of BMN 165 over time in relation to plasma phenylalanine level [ Time Frame: Part 3 Week 9 ] [ Designated as safety issue: No ]
    Blood samples collected at 4 time points during Part 3 Week 9 to evaluate the multiple-dose PK/PD of BMN 165.

Estimated Enrollment: 120
Study Start Date: July 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BMN165 20mg/day
BMN165 20mg/day self-administered daily
Drug: BMN165 20mg/day
Two different doses of BMN165 compared to eachother and compared to placebo
Other Name: PEG-PAL
Placebo Comparator: Low Placebo
Low Placebo self-administered daily
Drug: Placebo
Other Name: Dextran 40
Active Comparator: BMN165 40mg/day
BMN165 40mg/day self-administered daily
Drug: BMN165 40mg/day
Other Name: PEG-PAL
Placebo Comparator: High Placebo
High Placebo self-administered daily
Drug: Placebo
Other Name: Dextran 40

Detailed Description:

Study BMN 165-302 is a Phase 3, 3 Part/4 armed, Randomized, Double-Blind, Placebo-Controlled, Discontinuation Study to Evaluate the Efficacy and Safety of Self Administered Subcutaneous Injections of BMN 165 by Adults With PKU.

In contrast to BMN study 165-301 (currently recruiting) which is open to adults who are naive to BMN165, this study is open only to adults who have been exposed to BMN165 in a previous study.

Study BMN 165-302 is a three-part, Phase 3 study.

Part 1 is an open-label run-in period designed to stabilize the dosing regimen of subjects who enroll from a previous BMN 165 study.

Part 2 is a double-blind, placebo-controlled, four-arm, discontinuation study designed to compare the blood Phe concentrations of subjects who continue administration with BMN 165 versus those of subjects who temporarily receive placebo.

Part 3 is a long-term, open-label extension study designed to evaluate the long-term efficacy and safety of BMN 165 and to provide long-term access to BMN 165 (no placebo).


Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Individuals eligible to participate in this study must meet all of the following criteria:

  • Have completed at least 14 weeks of administration with BMN 165 prior to screening
  • Have had a stable BMN 165 dose for at least 28 days prior to screening
  • Are at least 16 years of age and no older than 70 years of age at the time of screening
  • 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; for minors, parent or guardian provides written consent and assent may be requested
  • Are willing and able to comply with all study procedures
  • 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 two acceptable methods of contraception while participating in the study
  • Have maintained their diet (including medical formula) with no significant modifications during the 4 weeks prior to randomization and are willing to maintain their current diet and, if needed, adjust their dietary and/or medical food protein intake according to the study protocol
  • Have cognitive and linguistic capacities to complete the cognitive and mood questionnaires
  • If applicable, maintained stable dose of medication for 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 (hematology, chemistry, and urinalysis), and ECG tests performed at screening

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:

  • Use of any investigational product (except BMN 165) 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 (except BMN 165) intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of study drug (Day 1, first dose of BMN 165)
  • Have known hypersensitivity to any component of BMN 165
  • Have known hypersensitivity to Dextran or components of Dextran
  • 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
  • Current use of levodopa
  • A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody (subjects without screens during previous BMN 165 study)
  • A history of organ transplantation or on chronic immunosuppressive therapy
  • A history of substance abuse (as defined by the 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 at least 1.5 times the upper limit of normal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01889862

  Hide Study Locations
United States, California
University of California, San Diego School of Medicine
La Jolla, California, United States, 92103
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of South Florida
Tampa, Florida, United States, 3606
United States, Illinois
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Children's Hospital
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
University of Louisville, Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65212
Washington University Center for Applied Research Sciences
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Cooper Health Systems
Camden, New Jersey, United States, 08103
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Mount Sinai Medical Center
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14642
Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73140
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Houston Medical School
Houston, Texas, United States, 77030
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
United States, Washington
Unversity of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
BioMarin Pharmaceutical
Study Director: Markus Merilainen, MD BioMarin Pharmaceutical
  More Information

Additional Information:
No publications provided

Responsible Party: BioMarin Pharmaceutical Identifier: NCT01889862     History of Changes
Other Study ID Numbers: 165-302
Study First Received: June 18, 2013
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by BioMarin Pharmaceutical:

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases processed this record on July 26, 2014