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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01889862
First Posted: July 1, 2013
Last Update Posted: December 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
BioMarin Pharmaceutical
June 18, 2013
July 1, 2013
December 1, 2017
July 2013
December 31, 2018   (Final data collection date for primary outcome measure)
Incidence of adverse events experienced by subjects. [ Time Frame: Weekly throughout study. ]
Subjects will be assessed weekly for adverse events, including laboratory abnormalities.
  • Incidence of adverse events experienced by subjects. [ Time Frame: Weekly throughout study, an expected average of 3 years ]
    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 ]
    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).
Complete list of historical versions of study NCT01889862 on ClinicalTrials.gov Archive Site
  • Cognitive and mood symptoms BMN 165 [ Time Frame: Throughout the study ]
    ADHD-RS IV and the POMS (Profile of Mood States) will be used to evaluate cognitive and mood symptoms.
  • Plasma Phenylalanine (phe) levels [ Time Frame: Throughout the study ]
Cognitive and mood symptoms at Part 2 Week 8 in subjects on placebo versus BMN 165 [ Time Frame: Part 2 Week 8 ]
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.
Protein intake as reported by subjects in diet diary [ Time Frame: Every 4 weeks, an expected average of 3 years ]
Diet diary collected monthly to assess protein intake from medical food and from natural protein.
  • Protein intake as reported by subjects in diet diary [ Time Frame: Every 4 weeks, an expected average of 3 years ]
    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 ]
    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 ]
    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 ]
    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 ]
    Blood samples collected at 4 time points during Part 3 Week 9 to evaluate the multiple-dose PK/PD of BMN 165.
 
Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
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)
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.

165-302 is a Phase 3, 4 Part, 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: PK (plasma BMN 165) and PD (plasma Phe) assessment.
  • Part 4: A long-term, open-label extension study.
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Phenylketonuria (PKU)
  • Drug: BMN165 20mg/day
    Two different doses of BMN165 compared to each other and compared to placebo
    Other Name: PEG-PAL
  • Drug: BMN165 40mg/day
    Two different doses of BMN165 compared to each other and compared to placebo
    Other Name: PEG-PAL
  • Drug: Placebo
    Two different doses of BMN165 compared to each other and compared to placebo
    Other Name: Dextran 40
  • Active Comparator: BMN165 20mg/day
    BMN165 20mg/day self-administered daily
    Intervention: Drug: BMN165 20mg/day
  • Placebo Comparator: Low Placebo
    Low Placebo self-administered daily
    Intervention: Drug: Placebo
  • Active Comparator: BMN165 40mg/day
    BMN165 40mg/day self-administered daily
    Intervention: Drug: BMN165 40mg/day
  • Placebo Comparator: High Placebo
    High Placebo self-administered daily
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
250
March 31, 2019
December 31, 2018   (Final data collection date for primary outcome measure)

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

    • Males post vasectomy for 2 years with no known pregnancies do not need to use any other forms of contraception 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 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
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01889862
165-302
Yes
Not Provided
Plan to Share IPD: No
BioMarin Pharmaceutical
BioMarin Pharmaceutical
Not Provided
Study Director: Markus Merilainen, MD BioMarin Pharmaceutical
BioMarin Pharmaceutical
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP