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

• 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: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Phenylketonuria
• Intervention: Biological: BMN 165 (rAvPAL-PEG)
• Enrollment: 24

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	BMN 165 (rAvPAL-PEG)
Arm/Group Description	[Not Specified]
Period Title: Overall Study
Started	24
Completed	24
Not Completed	0

Baseline Characteristics

Arm/Group Title		rAvPAL-PEG
Arm/Group Description		All 24 Enrolled Subjects
Overall Number of Baseline Participants		24
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%

Outcome Measures

1. Primary Outcome

Title	Blood Phenylalanine Concentration
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

Outcome Measure Data

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
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
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):

Outcome Measure Data

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
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]
Description	Antibody Positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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
Description	PK assessment from pre-dose blood draw.
Time Frame	Week 1, Week 24

Outcome Measure Data

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
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
Description	Antibody Positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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
Description	Antibody Positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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
Description	Antibody positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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]
Description	Antibody positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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
Description	Antibody positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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
Description	Antibody positivity
Time Frame	Baseline, Week 24

Outcome Measure Data

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
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

Adverse Events

Time Frame	Week 0- Week 24
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	rAvPAL-PEG
Arm/Group Description	All 24 Enrolled Subjects
All-Cause Mortality
	rAvPAL-PEG
	Affected / at Risk (%)
Total	0/24 (0.00%)
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
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

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

• Name/Title: Sr. Medical Director, Clinical Science
• Organization: BioMarin Pharmaceutical Inc
• Phone: 415-475-5854
• EMail: Ari.Gershman@bmrn.com

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01560286
• 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