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A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks

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.
 
ClinicalTrials.gov Identifier: NCT01560286
Recruitment Status : Completed
First Posted : March 22, 2012
Results First Posted : February 27, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Phenylketonuria
Intervention Biological: BMN 165 (rAvPAL-PEG)
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title BMN 165 (rAvPAL-PEG)
Hide Arm/Group Description [Not Specified]
Period Title: Overall Study
Started 24
Completed 24
Not Completed 0
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description All 24 Enrolled Subjects
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
29.3  (11.43)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
< 18 years
1
   4.2%
> or = 18 years
23
  95.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
13
  54.2%
Male
11
  45.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
24
 100.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
24
 100.0%
Other
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
 100.0%
1.Primary Outcome
Title Blood Phenylalanine Concentration
Hide Description All patients will have their plasma Phenylalanine (Phe) assessed. Please note that "Pharmacokinetics Sub-study" was not performed, and thus no results are available.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population will consist of all subjects who received any amount of study drug and have post-treatment blood Phe concentration measurements.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: umol/L
Baseline 1168.8  (290.98)
Week 24 617.6  (529.28)
2.Secondary Outcome
Title Number of Participants With Study Drug Related Adverse Events
Hide Description [Not Specified]
Time Frame Minimum Weekly Assessment of Injection Sites, Vital Signs and Adverse Events. Other Safety Assessments will be performed at other intervals (below):
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
23
  95.8%
3.Secondary Outcome
Title Percentage of Participants With Positive Anti-PAL Immunoglobulin G [IgG]
Hide Description Antibody Positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 4.3
Week 24 95.5
4.Secondary Outcome
Title Trough Concentration of BMN 165
Hide Description PK assessment from pre-dose blood draw.
Time Frame Week 1, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population will consist of all subjects who received any amount of study drug and have post-treatment plasma BMN 165 concentration measurements.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 1 Day 1 0.2  (1.09)
Week 24 2341.1  (4768.28)
5.Secondary Outcome
Title Percentage of Participants With Positive Anti-PEG IgG
Hide Description Antibody Positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 26.1
Week 24 22.7
6.Secondary Outcome
Title Percentage of Participants With Positive PAL-IgM
Hide Description Antibody Positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 34.8
Week 24 90.9
7.Secondary Outcome
Title Percentage of Participants With Positive Anti-PEG-IgM
Hide Description Antibody positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 4.3
Week 24 9.1
8.Secondary Outcome
Title Percentage of Participants With Positive Neutralizing Antibodies [Nab]
Hide Description Antibody positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 0
Week 24 27.3
9.Secondary Outcome
Title Percentage of Participants With Positive Anti-PAL-IgE Antibodies
Hide Description Antibody positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 0
Week 24 0
10.Secondary Outcome
Title Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies
Hide Description Antibody positivity
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population will consist of all subjects who receive any amount of study drug throughout the study duration.
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description:
All 24 Enrolled Subjects
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage
Baseline 0
Week 24 0
Time Frame Week 0- Week 24
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title rAvPAL-PEG
Hide Arm/Group Description All 24 Enrolled Subjects
All-Cause Mortality
rAvPAL-PEG
Affected / at Risk (%)
Total   0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
rAvPAL-PEG
Affected / at Risk (%) # Events
Total   1/24 (4.17%)    
Investigations   
Blood creatine phosphokinase increased  1  1/24 (4.17%)  1
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
rAvPAL-PEG
Affected / at Risk (%) # Events
Total   23/24 (95.83%)    
Blood and lymphatic system disorders   
Lymphadenopathy  1  2/24 (8.33%)  2
Gastrointestinal disorders   
Diarrhoea  1  3/24 (12.50%)  3
Dyspepsia  1  2/24 (8.33%)  2
Nausea  1  8/24 (33.33%)  9
Toothache  1  2/24 (8.33%)  2
Vomiting  1  3/24 (12.50%)  5
General disorders   
Injection site bruising  1  10/24 (41.67%)  13
Injection site erythema  1  13/24 (54.17%)  40
Injection site induration  1  2/24 (8.33%)  2
Injection site pruritus  1  5/24 (20.83%)  11
Injection site rash  1  8/24 (33.33%)  16
Injection site reaction  1  18/24 (75.00%)  123
Injection site swelling  1  3/24 (12.50%)  5
Injection site urticaria  1  2/24 (8.33%)  3
Local swelling  1  2/24 (8.33%)  4
Mass  1  2/24 (8.33%)  2
Pain  1  2/24 (8.33%)  2
Pyrexia  1  6/24 (25.00%)  8
Immune system disorders   
Seasonal allergy  1  2/24 (8.33%)  5
Infections and infestations   
Nasopharyngitis  1  4/24 (16.67%)  4
Oral herpes  1  2/24 (8.33%)  2
Rhinovirus infection  1  2/24 (8.33%)  3
Sinusitis  1  2/24 (8.33%)  2
Upper respiratory tract infection  1  9/24 (37.50%)  10
Investigations   
C-reactive protein increased  1  3/24 (12.50%)  3
Complement factor decreased  1  2/24 (8.33%)  2
Red blood cell sedimentation rate increased  1  2/24 (8.33%)  2
Urine albumin/creatinine ratio increased  1  2/24 (8.33%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  18/24 (75.00%)  80
Back pain  1  3/24 (12.50%)  8
Joint swelling  1  2/24 (8.33%)  3
Musculoskeletal pain  1  3/24 (12.50%)  3
Myalgia  1  3/24 (12.50%)  4
Pain in extremity  1  3/24 (12.50%)  3
Pain in jaw  1  2/24 (8.33%)  2
Nervous system disorders   
Dizziness  1  4/24 (16.67%)  5
Headache  1  7/24 (29.17%)  12
Sinus headache  1  2/24 (8.33%)  2
Psychiatric disorders   
Anxiety  1  3/24 (12.50%)  4
Depression  1  2/24 (8.33%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/24 (20.83%)  5
Dyspnoea  1  3/24 (12.50%)  8
Oropharyngeal pain  1  2/24 (8.33%)  2
Skin and subcutaneous tissue disorders   
Dermatitis contact  1  2/24 (8.33%)  2
Erythema  1  2/24 (8.33%)  3
Hyperhidrosis  1  2/24 (8.33%)  2
Pruritus  1  5/24 (20.83%)  6
Rash  1  8/24 (33.33%)  13
Rash generalised  1  5/24 (20.83%)  10
Rash pruritic  1  2/24 (8.33%)  2
Urticaria  1  3/24 (12.50%)  6
Vascular disorders   
Flushing  1  4/24 (16.67%)  5
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. Medical Director, Clinical Science
Organization: BioMarin Pharmaceutical Inc
Phone: 415-475-5854
EMail: Ari.Gershman@bmrn.com
Layout table for additonal information
Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01560286     History of Changes
Other Study ID Numbers: 165-205
First Submitted: March 5, 2012
First Posted: March 22, 2012
Results First Submitted: June 22, 2018
Results First Posted: February 27, 2019
Last Update Posted: August 6, 2019