Trial Outcomes & Findings for An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 (NCT NCT01819727)
NCT ID: NCT01819727
Last Updated: 2019-02-26
Results Overview
Hypersensitivity AEs will be identified in two ways: * Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ) * Modified Hypersensitivity SMQ to include above additional preferred terms
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
261 participants
Primary outcome timeframe
baseline and 36 weeks
Results posted on
2019-02-26
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Overall Study
STARTED
|
131
|
130
|
|
Overall Study
COMPLETED
|
111
|
102
|
|
Overall Study
NOT COMPLETED
|
20
|
28
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
8
|
9
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Physician Decision
|
3
|
2
|
|
Overall Study
Pregnancy
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Study Terminated by Sponsor
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
11
|
|
Overall Study
Unable to demostrate ability self-inject
|
0
|
1
|
|
Overall Study
Quit due to lack of health benifits
|
0
|
1
|
Baseline Characteristics
An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
Baseline characteristics by cohort
| Measure |
BMN 165, 20mg/Day
n=131 Participants
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
n=130 Participants
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
n=261 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30.2 years
STANDARD_DEVIATION 8.63 • n=5 Participants
|
28.1 years
STANDARD_DEVIATION 8.77 • n=7 Participants
|
29.2 years
STANDARD_DEVIATION 8.75 • n=5 Participants
|
|
Age, Customized
16 - <18 years
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Customized
18 - <66 years
|
126 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
250 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
62 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
125 Participants
n=5 Participants
|
128 Participants
n=7 Participants
|
253 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
130 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
254 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
131 Participants
n=5 Participants
|
130 Participants
n=7 Participants
|
261 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 36 weeksPopulation: The safety population will consist of all subjects who receive any pegvaliase throughout the study duration. The safety population will be analyzed according to the treatment assignment actually received.
Hypersensitivity AEs will be identified in two ways: * Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ) * Modified Hypersensitivity SMQ to include above additional preferred terms
Outcome measures
| Measure |
BMN 165, 20mg/Day
n=131 Participants
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
n=130 Participants
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.
|
|---|---|---|
|
Number of Participants With Hypersensitivity Adverse Reaction
|
111 Participants
|
119 Participants
|
SECONDARY outcome
Timeframe: baseline and 36 weeksPopulation: The intent-to-treat (ITT) population will consist of all subjects who are randomized to study treatment whether or not treatment was received.
Plasma phenylalanine (Phe) concentration
Outcome measures
| Measure |
BMN 165, 20mg/Day
n=131 Participants
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
n=130 Participants
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.
|
|---|---|---|
|
Blood Phenylalanine Concentration
Week 36
|
868.4 umol/L
Standard Deviation 501.78
|
624.4 umol/L
Standard Deviation 530.58
|
|
Blood Phenylalanine Concentration
Baseline
|
1241.0 umol/L
Standard Deviation 389.70
|
1224.4 umol/L
Standard Deviation 384.28
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 36 weeksPopulation: The intent-to-treat (ITT) population will consist of all subjects who are randomized to study treatment whether or not treatment was received.
All patients will complete a 3-day diet diary in order to assess dietary phenylalanine intake.
Outcome measures
| Measure |
BMN 165, 20mg/Day
n=131 Participants
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
n=130 Participants
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.
|
|---|---|---|
|
Dietary Phenylalanine
Baseline
|
1750.8 mg
Standard Deviation 1168.91
|
1647.9 mg
Standard Deviation 1222.68
|
|
Dietary Phenylalanine
Week 36
|
1851.8 mg
Standard Deviation 1145.06
|
2057.9 mg
Standard Deviation 1448.21
|
Adverse Events
BMN 165, 20mg/Day
Serious events: 7 serious events
Other events: 130 other events
Deaths: 1 deaths
BMN 165, 40mg/Day
Serious events: 19 serious events
Other events: 129 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BMN 165, 20mg/Day
n=131 participants at risk
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
n=130 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
General disorders
Electrocution
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.00%
0/130 • Week 0- Week 36
|
|
General disorders
Injection site reaction
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.00%
0/130 • Week 0- Week 36
|
|
General disorders
Puncture site haemorrhage
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Immune system disorders
Anaphylactic reaction
|
1.5%
2/131 • Number of events 2 • Week 0- Week 36
|
4.6%
6/130 • Number of events 6 • Week 0- Week 36
|
|
Immune system disorders
Anaphylactoid reaction
|
0.00%
0/131 • Week 0- Week 36
|
1.5%
2/130 • Number of events 2 • Week 0- Week 36
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/131 • Week 0- Week 36
|
2.3%
3/130 • Number of events 3 • Week 0- Week 36
|
|
Immune system disorders
Serum sickness
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Investigations
Blood creatine phosphokinase increased
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papilloma
|
0.00%
0/131 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Pregnancy, puerperium and perinatal conditions
Abortion missed
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.00%
0/130 • Week 0- Week 36
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/131 • Week 0- Week 36
|
1.5%
2/130 • Number of events 2 • Week 0- Week 36
|
|
Vascular disorders
Deep vein thrombosis
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
0.00%
0/130 • Week 0- Week 36
|
Other adverse events
| Measure |
BMN 165, 20mg/Day
n=131 participants at risk
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
n=130 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
9.2%
12/131 • Number of events 21 • Week 0- Week 36
|
7.7%
10/130 • Number of events 18 • Week 0- Week 36
|
|
Gastrointestinal disorders
Abdominal discomfort
|
8.4%
11/131 • Number of events 13 • Week 0- Week 36
|
3.8%
5/130 • Number of events 5 • Week 0- Week 36
|
|
Gastrointestinal disorders
Abdominal pain
|
6.9%
9/131 • Number of events 10 • Week 0- Week 36
|
3.8%
5/130 • Number of events 8 • Week 0- Week 36
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.6%
10/131 • Number of events 13 • Week 0- Week 36
|
3.8%
5/130 • Number of events 6 • Week 0- Week 36
|
|
Gastrointestinal disorders
Diarrhoea
|
9.9%
13/131 • Number of events 16 • Week 0- Week 36
|
8.5%
11/130 • Number of events 13 • Week 0- Week 36
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
8/131 • Number of events 13 • Week 0- Week 36
|
6.9%
9/130 • Number of events 11 • Week 0- Week 36
|
|
Gastrointestinal disorders
Nausea
|
22.1%
29/131 • Number of events 38 • Week 0- Week 36
|
16.9%
22/130 • Number of events 28 • Week 0- Week 36
|
|
Gastrointestinal disorders
Vomiting
|
16.0%
21/131 • Number of events 33 • Week 0- Week 36
|
12.3%
16/130 • Number of events 20 • Week 0- Week 36
|
|
General disorders
Chills
|
11.5%
15/131 • Number of events 22 • Week 0- Week 36
|
6.9%
9/130 • Number of events 13 • Week 0- Week 36
|
|
General disorders
Fatigue
|
16.0%
21/131 • Number of events 58 • Week 0- Week 36
|
10.0%
13/130 • Number of events 27 • Week 0- Week 36
|
|
General disorders
Injection site bruising
|
18.3%
24/131 • Number of events 65 • Week 0- Week 36
|
20.0%
26/130 • Number of events 44 • Week 0- Week 36
|
|
General disorders
Injection site erythema
|
43.5%
57/131 • Number of events 323 • Week 0- Week 36
|
46.9%
61/130 • Number of events 210 • Week 0- Week 36
|
|
General disorders
Injection site haemorrhage
|
5.3%
7/131 • Number of events 9 • Week 0- Week 36
|
3.1%
4/130 • Number of events 6 • Week 0- Week 36
|
|
General disorders
Injection site oedema
|
0.00%
0/131 • Week 0- Week 36
|
5.4%
7/130 • Number of events 112 • Week 0- Week 36
|
|
General disorders
Injection site pain
|
20.6%
27/131 • Number of events 63 • Week 0- Week 36
|
22.3%
29/130 • Number of events 55 • Week 0- Week 36
|
|
General disorders
Injection site pruritus
|
22.1%
29/131 • Number of events 87 • Week 0- Week 36
|
27.7%
36/130 • Number of events 119 • Week 0- Week 36
|
|
General disorders
Injection site rash
|
16.8%
22/131 • Number of events 96 • Week 0- Week 36
|
21.5%
28/130 • Number of events 66 • Week 0- Week 36
|
|
General disorders
Injection site reaction
|
61.1%
80/131 • Number of events 700 • Week 0- Week 36
|
52.3%
68/130 • Number of events 495 • Week 0- Week 36
|
|
General disorders
Injection site swelling
|
17.6%
23/131 • Number of events 70 • Week 0- Week 36
|
15.4%
20/130 • Number of events 45 • Week 0- Week 36
|
|
General disorders
Injection site urticaria
|
7.6%
10/131 • Number of events 27 • Week 0- Week 36
|
10.8%
14/130 • Number of events 25 • Week 0- Week 36
|
|
General disorders
Oedema peripheral
|
4.6%
6/131 • Number of events 7 • Week 0- Week 36
|
6.9%
9/130 • Number of events 22 • Week 0- Week 36
|
|
General disorders
Pain
|
16.8%
22/131 • Number of events 31 • Week 0- Week 36
|
5.4%
7/130 • Number of events 11 • Week 0- Week 36
|
|
General disorders
Pyrexia
|
19.8%
26/131 • Number of events 43 • Week 0- Week 36
|
6.2%
8/130 • Number of events 13 • Week 0- Week 36
|
|
Immune system disorders
Hypersensitivity
|
3.1%
4/131 • Number of events 4 • Week 0- Week 36
|
5.4%
7/130 • Number of events 7 • Week 0- Week 36
|
|
Infections and infestations
Nasopharyngitis
|
18.3%
24/131 • Number of events 33 • Week 0- Week 36
|
19.2%
25/130 • Number of events 29 • Week 0- Week 36
|
|
Infections and infestations
Sinusitis
|
6.9%
9/131 • Number of events 10 • Week 0- Week 36
|
10.0%
13/130 • Number of events 13 • Week 0- Week 36
|
|
Infections and infestations
Upper respiratory tract infection
|
16.8%
22/131 • Number of events 27 • Week 0- Week 36
|
15.4%
20/130 • Number of events 24 • Week 0- Week 36
|
|
Injury, poisoning and procedural complications
Contusion
|
13.0%
17/131 • Number of events 26 • Week 0- Week 36
|
6.9%
9/130 • Number of events 11 • Week 0- Week 36
|
|
Investigations
Blood cortisol decreased
|
0.76%
1/131 • Number of events 1 • Week 0- Week 36
|
6.2%
8/130 • Number of events 8 • Week 0- Week 36
|
|
Investigations
Blood creatine phosphokinase increased
|
5.3%
7/131 • Number of events 7 • Week 0- Week 36
|
3.1%
4/130 • Number of events 4 • Week 0- Week 36
|
|
Investigations
C-reactive protein increased
|
9.2%
12/131 • Number of events 16 • Week 0- Week 36
|
7.7%
10/130 • Number of events 10 • Week 0- Week 36
|
|
Investigations
Complement factor C3 decreased
|
8.4%
11/131 • Number of events 12 • Week 0- Week 36
|
5.4%
7/130 • Number of events 7 • Week 0- Week 36
|
|
Investigations
Complement factor C4 decreased
|
9.2%
12/131 • Number of events 12 • Week 0- Week 36
|
4.6%
6/130 • Number of events 6 • Week 0- Week 36
|
|
Investigations
Red blood cell sedimentation rate increased
|
5.3%
7/131 • Number of events 8 • Week 0- Week 36
|
0.77%
1/130 • Number of events 1 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
59.5%
78/131 • Number of events 376 • Week 0- Week 36
|
70.8%
92/130 • Number of events 350 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.0%
21/131 • Number of events 34 • Week 0- Week 36
|
15.4%
20/130 • Number of events 26 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
6.1%
8/131 • Number of events 9 • Week 0- Week 36
|
4.6%
6/130 • Number of events 10 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
6.1%
8/131 • Number of events 15 • Week 0- Week 36
|
3.8%
5/130 • Number of events 6 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
9.2%
12/131 • Number of events 18 • Week 0- Week 36
|
14.6%
19/130 • Number of events 24 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.2%
12/131 • Number of events 18 • Week 0- Week 36
|
4.6%
6/130 • Number of events 9 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.8%
5/131 • Number of events 7 • Week 0- Week 36
|
7.7%
10/130 • Number of events 12 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.3%
20/131 • Number of events 42 • Week 0- Week 36
|
20.0%
26/130 • Number of events 52 • Week 0- Week 36
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
6.1%
8/131 • Number of events 9 • Week 0- Week 36
|
4.6%
6/130 • Number of events 8 • Week 0- Week 36
|
|
Nervous system disorders
Dizziness
|
15.3%
20/131 • Number of events 24 • Week 0- Week 36
|
16.2%
21/130 • Number of events 32 • Week 0- Week 36
|
|
Nervous system disorders
Headache
|
35.1%
46/131 • Number of events 112 • Week 0- Week 36
|
27.7%
36/130 • Number of events 98 • Week 0- Week 36
|
|
Psychiatric disorders
Anxiety
|
3.1%
4/131 • Number of events 11 • Week 0- Week 36
|
7.7%
10/130 • Number of events 11 • Week 0- Week 36
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.4%
11/131 • Number of events 12 • Week 0- Week 36
|
7.7%
10/130 • Number of events 13 • Week 0- Week 36
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.9%
9/131 • Number of events 10 • Week 0- Week 36
|
5.4%
7/130 • Number of events 7 • Week 0- Week 36
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.8%
22/131 • Number of events 23 • Week 0- Week 36
|
9.2%
12/130 • Number of events 14 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.1%
8/131 • Number of events 8 • Week 0- Week 36
|
9.2%
12/130 • Number of events 12 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.4%
11/131 • Number of events 17 • Week 0- Week 36
|
9.2%
12/130 • Number of events 28 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.8%
22/131 • Number of events 39 • Week 0- Week 36
|
19.2%
25/130 • Number of events 65 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.6%
27/131 • Number of events 68 • Week 0- Week 36
|
30.8%
40/130 • Number of events 83 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
2.3%
3/131 • Number of events 3 • Week 0- Week 36
|
6.2%
8/130 • Number of events 17 • Week 0- Week 36
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
13.7%
18/131 • Number of events 71 • Week 0- Week 36
|
23.1%
30/130 • Number of events 101 • Week 0- Week 36
|
Additional Information
Principal Scientist I, Clinical Sciences
BioMarin Pharmaceutical Inc.
Phone: 415-506-6348
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60