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Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU (Prism-2)

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ClinicalTrials.gov Identifier: NCT01889862
Recruitment Status : Completed
First Posted : July 1, 2013
Results First Posted : July 12, 2019
Last Update Posted : May 21, 2021
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief 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 adults with PKU.

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

Detailed Description:

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: Two sub-Parts to Part 3:- Part 3A - BMN 165 administered using vial and syringe during this open label period. Part 3B - BMN 165 administered using prefilled syringe during this open-label period.
  • Part 4: A long-term, open-label extension period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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)
Actual Study Start Date : July 29, 2013
Actual Primary Completion Date : January 13, 2016
Actual Study Completion Date : February 5, 2019


Arm Intervention/treatment
Active Comparator: BMN165 20mg/day
BMN165 20mg/day self-administered daily
Drug: BMN165 20mg/day
BMN165 20mg/day self-administered daily
Other Name: PEG-PAL

Placebo Comparator: 20 mg/day Placebo
20 mg/day Placebo self-administered daily
Drug: Placebo
Non-drug placebo, self-administered daily
Other Name: Dextran 40

Active Comparator: BMN165 40mg/day
BMN165 40mg/day self-administered daily
Drug: BMN165 40mg/day
BMN165 40mg/day self-administered daily
Other Name: PEG-PAL

Placebo Comparator: 40 mg/day Placebo
40 mg/day Placebo self-administered daily
Drug: Placebo
Non-drug placebo, self-administered daily
Other Name: Dextran 40




Primary Outcome Measures :
  1. Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 [ Time Frame: At Part 2 baseline and change from baseline at Part 2 week 8 ]
    Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo.


Secondary Outcome Measures :
  1. Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 [ Time Frame: At Part 2 baseline and change from baseline at Part 2 week 8 ]
    Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score >9 indicative of a presence of symptoms.

  2. Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 [ Time Frame: At Part 4 week 57, 105, 161, 209 and 249 ]
    The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes.

  3. Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 [ Time Frame: At Part 2 baseline and change from baseline at Part 2 week 8 ]

    Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS)

    PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).


  4. Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 [ Time Frame: At Part 2 baseline and change from baseline at Part 2 week 8 ]
    PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).

  5. Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 [ Time Frame: At Part 2 baseline and change from baseline at Part 2 week 8 ]
    Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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, 165-205, 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 Profile of Mood States (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 Attention Deficit Hyperactivity Disorder Rating Scale (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 ≥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
  • Alanine aminotransferase (ALT) concentration at least 2x the upper limit of normal
  • Creatinine at least 1.5x the upper limit of normal

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01889862


Locations
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Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Clinical Trial Specialist BioMarin Pharmaceutical
Additional Information:
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01889862    
Other Study ID Numbers: 165-302
First Posted: July 1, 2013    Key Record Dates
Results First Posted: July 12, 2019
Last Update Posted: May 21, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by BioMarin Pharmaceutical:
PKU
PEG-PAL
Prism
BioMarin
rAvPAL-PEG
BMN165
Additional relevant MeSH terms:
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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
Dextrans
Anticoagulants
Plasma Substitutes
Blood Substitutes