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An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 (Prism301)

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ClinicalTrials.gov Identifier: NCT01819727
Recruitment Status : Completed
First Posted : March 28, 2013
Results First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Phenylketonuria
Intervention: Drug: BMN 165

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
BMN 165, 20mg/Day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 or 40 mg/day. Randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600-900 μmol/L and > 900 μmol/L). All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the IP, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly dose to a daily dose regimen of 20 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 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 26 weeks-36 weeks in the study.
BMN 165, 40mg/Day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 or 40 mg/day. Randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600-900 μmol/L and > 900 μmol/L). All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the IP, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly dose to a daily dose regimen of 20 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 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 26 weeks-36 weeks in the study.

Participant Flow:   Overall Study
    BMN 165, 20mg/Day   BMN 165, 40mg/Day
STARTED   131   130 
COMPLETED   111   102 
NOT COMPLETED   20   28 
Adverse Event                8                9 
Death                1                0 
Lost to Follow-up                1                1 
Physician Decision                3                2 
Pregnancy                1                0 
Protocol Violation                0                2 
Study Terminated by Sponsor                0                1 
Withdrawal by Subject                6                11 
Unable to demostrate ability self-inject                0                1 
Quit due to lack of health benifits                0                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
BMN 165, 20mg/Day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 or 40 mg/day. Randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600-900 μmol/L and > 900 μmol/L). All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the IP, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly dose to a daily dose regimen of 20 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 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 26 weeks-36 weeks in the study.
BMN 165, 40mg/Day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 or 40 mg/day. Randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600-900 μmol/L and > 900 μmol/L). All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction). After the IP, subjects will enter the Titration Period (Weeks 5 up to 34) where they will increase their weekly dose to a daily dose regimen of 20 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 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 26 weeks-36 weeks in the study.
Total Total of all reporting groups

Baseline Measures
   BMN 165, 20mg/Day   BMN 165, 40mg/Day   Total 
Overall Participants Analyzed 
[Units: Participants]
 131   130   261 
Age 
[Units: Years]
Mean (Standard Deviation)
 30.2  (8.63)   28.1  (8.77)   29.2  (8.75) 
Age, Customized 
[Units: Participants]
Count of Participants
     
16 - <18 years   5   6   11 
18 - <66 years   126   124   250 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      62  47.3%      68  52.3%      130  49.8% 
Male      69  52.7%      62  47.7%      131  50.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      6   4.6%      1   0.8%      7   2.7% 
Not Hispanic or Latino      125  95.4%      128  98.5%      253  96.9% 
Unknown or Not Reported      0   0.0%      1   0.8%      1   0.4% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native   0   1   1 
Asian   0   0   0 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   1   2   3 
White   130   124   254 
Other   0   2   2 
Region of Enrollment 
[Units: Participants]
Count of Participants
     
United States   131   130   261 


  Outcome Measures

1.  Primary:   Number of Participants With Hypersensitivity Adverse Reaction   [ Time Frame: baseline and 36 weeks ]

2.  Secondary:   Blood Phenylalanine Concentration   [ Time Frame: baseline and 36 weeks ]

3.  Other Pre-specified:   Dietary Phenylalanine   [ Time Frame: baseline and 36 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Principal Scientist I, Clinical Sciences
Organization: BioMarin Pharmaceutical Inc.
phone: 415-506-6348
e-mail: dlounsbury@bmrn.com



Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01819727     History of Changes
Other Study ID Numbers: 165-301
Prism301 ( Other Identifier: Phase 3 "brand" name )
First Submitted: March 18, 2013
First Posted: March 28, 2013
Results First Submitted: June 22, 2018
Results First Posted: September 10, 2018
Last Update Posted: September 10, 2018