Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU (Prism302)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01889862
First received: June 18, 2013
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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)
Primary Purpose: Treatment
Official Title: A Four-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 (PKU)

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. ] [ Designated as safety issue: Yes ]
    Subjects will be assessed weekly for adverse events, including laboratory abnormalities.


Secondary Outcome Measures:
  • Cognitive and mood symptoms BMN 165 [ Time Frame: Throughout the study ] [ 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 compared with subjects who self administer a placebo.

  • Plasma Phenylalanine (phe) levels [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
    phe levels will be assessed on subjects taking BMN 165, placebo, administering the study drug using vial and syringe as well as using pre-filled syringe.


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.


Estimated Enrollment: 250
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 each other and compared to placebo
Other Name: PEG-PAL
Placebo Comparator: Low Placebo
Low Placebo self-administered daily
Drug: Placebo
Two different doses of BMN165 compared to each other and compared to placebo
Other Name: Dextran 40
Active Comparator: BMN165 40mg/day
BMN165 40mg/day self-administered daily
Drug: BMN165 40mg/day
Two different doses of BMN165 compared to each other and compared to placebo
Other Name: PEG-PAL
Placebo Comparator: High Placebo
High Placebo self-administered daily
Drug: Placebo
Two different doses of BMN165 compared to each other and compared to placebo
Other Name: Dextran 40

Detailed Description:

165-302 is a Phase 3, 4 Part/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.

This study is open only to adults who have been exposed to BMN165 in a previous study.

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

  • PART 1: Open-label period
  • PART 2: A Randomized, double-blind, placebo-controlled period of 8 weeks
  • PART 3: Is a PK (plasma BMN 165) and PD (plasma Phe) assessment. During Part 3, subjects transition from vial and syringe to pre-filled syringe.
  • Part 4: A long-term, open-label extension study.
  Eligibility

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

INCLUSION CRITERIA

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

  • Have completed a prior BMN 165 study (PAL-003 or 165-301) prior to screening
  • Have had a stable BMN 165 dose regimen for at least 14 days prior to screening
  • Are at least 18 y/o and no older than 70 y/o at screening

    • Subjects who are < 18 y/o and are already enrolled into Study 165-301 under Amendment #1 (10JAN2014) may enroll into this study
  • Has identified a person who is ≥ 18 y/o who has the neurocognitive and linguistic capacities to comprehend and complete the POMS-Observer rated scale
  • Has identified a competent person(s) ≥ 18 y/o who can observe the subject during study drug administration at certain points in the study

    • A home healthcare nurse may perform the study drug observations
  • 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, a negative pregnancy test at screening and willing to have additional pregnancy tests during the study
  • If sexually active, willing to use two acceptable methods of contraception during and for 4 weeks after the study
  • Have received documented approval from a study dietitian confirming that the subject is capable of maintaining their diet
  • 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 ADHD, depression, anxiety, or other psychiatric disorder ≥8 weeks prior to enrollment and willing to maintain stable dose throughout study unless a change is medically indicated
  • General good health, as evidenced by physical examination, clinical laboratory evaluations, and ECG tests 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
  • Have known hypersensitivity to Dextran® or components of Dextran
  • Use or planned use of any injectable drugs containing PEG (except for 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
  • A history of organ transplantation or taking chronic immunosuppressive therapy
  • A history of substance abuse in the past 12 months or current alcohol or drug abuse
  • Current participation in the Kuvan registry study (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.
  • 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
  • ALT concentration at least 2x the upper limit of normal
  • Creatinine at least 1.5x 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 ClinicalTrials.gov identifier: NCT01889862

  Show 27 Study Locations
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Markus Merilainen, MD BioMarin Pharmaceutical
  More Information

Additional Information:
No publications provided

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

Keywords provided by BioMarin Pharmaceutical:
PKU
PEG-PAL
Prism
BioMarin
rAvPAL-PEG

Additional relevant MeSH terms:
Phenylketonurias
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

ClinicalTrials.gov processed this record on August 26, 2014