Clinical Trials List
Protocol Number307-201
NCT Number(ClinicalTrials.gov Identfier)NCT04480567
2021-02-01 - 2024-01-31
Phase I/II
Not yet recruiting2
ICD-10E70.0
Classical phenylketonuria
ICD-10E70.1
Other hyperphenylalaninemias
ICD-9270.1
Phenylketonuria﹝PKU﹞
A Phase 1/2 Open-Label, Dose Escalation Study to Determine the Safety and Efficacy of BMN 307, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Phenylalanine Hydroxylase in Subjects With Phenylketonuria
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Trial Applicant
MEDPACE TAIWAN LIMITED
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Sponsor
BioMarin Pharmaceutical, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 吳嘉峯 Division of Pediatrics
- SUSAN SHUR-FEN GAU Division of Psychiatry
- WUH-LIANG HWU Division of Pediatrics
- 吳嘉峰 Division of Pediatrics
- NI-CHUNG LEE Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Phenylketonuria (PKU)
Objectives
Part A Objective
•Determine safe, effective, and tolerable dose of BMN 307 in subjects with PKU ≥ 18 years of age with plasma Phe > 600 μmol/L at baseline for expanded dosing in Part B
Part B Primary Objective
•Determine the efficacy of a single administration of BMN 307 on plasma Phe in subjects with PKU≥ 15 years of age with plasma Phe > 600μmol/L at baseline
Test Drug
BMN 307
Active Ingredient
AAV5-ApoE-hAAT-LGi-hPAH-GENEius1
Dosage Form
IVT
Dosage
6e13 vg/mL BMN 307，8 mL/vial
Endpoints
Part A
•Proportion of subjects achieving plasma Phe milestones (ie, plasma Phe≤ 360 μmol/L and Phe ≤ 120 μmol/L) by Week 8 post-infusion of BMN 307 within each dose cohort.
•Change from baseline in mean plasma Phe levels at Week 8 post-infusion of BMN 307 within each dose cohort
•Treatment emergent adverse events
Part B
•Change from baseline in mean plasma Phe levels during Week 10 to Week 12 post-infusion
•Proportion of subjects achieving plasma Phe milestones (ie, plasma Phe≤ 360 μmol/L and Phe ≤ 120 μmol/L) by Week 8 post-infusion of BMN 307 within each dose cohort.
•Change from baseline in mean plasma Phe levels at Week 8 post-infusion of BMN 307 within each dose cohort
•Treatment emergent adverse events
Part B
•Change from baseline in mean plasma Phe levels during Week 10 to Week 12 post-infusion
Inclution Criteria
Key inclusion criteria include:
1.Diagnosis of PKU which is a condition characterized by PAH deficiency
2.Average of two plasma Phe levels >600 u/mol during the Screening period
3.Never received pharmacotherapy to treat PKU or if previously on pharmacotherapy to treat PKU, pharmacotherapy must have been discontinued due to lack of tolerability or inability to achieve target efficacy. Subjects should not discontinue effective treatment to enroll in 307-201. Subjects previously on pharmacotherapy must have discontinued prior to screening as outlined below: oLast dose of pegvaliase or large neutral amino acids (LNAAs) must have been at least 30 days prior to Screening oLast dose of sapropterin must have been at least 7 days prior to Screening
4.Ability and willingness to maintain dietary protein intake consistent with baseline intake for the duration of the study unless otherwise directed.
5.Sexually active male subjects must agree to use an acceptable method of effective contraception for at least 12 weeks post-BMN 307 administration. After 12 weeks, subjects may stop contraception use only if they have had 3 consecutive semen samples with no detectable viral vector DNA
6.Women of childbearing potential must have a negative serum pregnancy test at Day -28 and Day -7 and must agree to use an acceptable method of highly effective contraception from Screening through the end of the study.
1.Diagnosis of PKU which is a condition characterized by PAH deficiency
2.Average of two plasma Phe levels >600 u/mol during the Screening period
3.Never received pharmacotherapy to treat PKU or if previously on pharmacotherapy to treat PKU, pharmacotherapy must have been discontinued due to lack of tolerability or inability to achieve target efficacy. Subjects should not discontinue effective treatment to enroll in 307-201. Subjects previously on pharmacotherapy must have discontinued prior to screening as outlined below: oLast dose of pegvaliase or large neutral amino acids (LNAAs) must have been at least 30 days prior to Screening oLast dose of sapropterin must have been at least 7 days prior to Screening
4.Ability and willingness to maintain dietary protein intake consistent with baseline intake for the duration of the study unless otherwise directed.
5.Sexually active male subjects must agree to use an acceptable method of effective contraception for at least 12 weeks post-BMN 307 administration. After 12 weeks, subjects may stop contraception use only if they have had 3 consecutive semen samples with no detectable viral vector DNA
6.Women of childbearing potential must have a negative serum pregnancy test at Day -28 and Day -7 and must agree to use an acceptable method of highly effective contraception from Screening through the end of the study.
Exclusion Criteria
Key exclusion criteria include:
1.Subjects with primary BH4 deficiency or other forms of BH4 metabolism deficiency
2.Any evidence of an active infection or any immunosuppressive disorder, including HIV infection
3.Clinically significant liver disease as assessed by ultrasound at Screening
4.Grade 3 or Grade 4 fibrosis as assessed by either Fibroscan or Enhanced Liver Fibrosis (ELF) test score > 10.51 at Screening, as regionally available and/or approved by health authorities (HA).
5.Significant liver dysfunction at Screening
6.Prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0 to 4 on the Batts-Ludwig (Batts, 1995) or METAVIR (Bedossa, 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
7.Prior treatment with gene therapy
8.Use of systemic immunosuppressive agents, including corticosteroids, within 30 days prior to BMN 307 administration 9.Detectable antibodies to the AAV5 capsid at Screening
10.Substance use disorder and/or, active major depressive disorder (as defined by the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders 5th edition ([DSM-5], American Psychiatric Association, 2013) in the past 12 months prior to Screening.
11.Any history of psychosis or bipolar disorder (as defined by DSM-5).
12.Contraindication to use of corticosteroids (CS) or history of condition that could worsen with CS therapy, as assessed and determined by the investigator.
1.Subjects with primary BH4 deficiency or other forms of BH4 metabolism deficiency
2.Any evidence of an active infection or any immunosuppressive disorder, including HIV infection
3.Clinically significant liver disease as assessed by ultrasound at Screening
4.Grade 3 or Grade 4 fibrosis as assessed by either Fibroscan or Enhanced Liver Fibrosis (ELF) test score > 10.51 at Screening, as regionally available and/or approved by health authorities (HA).
5.Significant liver dysfunction at Screening
6.Prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0 to 4 on the Batts-Ludwig (Batts, 1995) or METAVIR (Bedossa, 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
7.Prior treatment with gene therapy
8.Use of systemic immunosuppressive agents, including corticosteroids, within 30 days prior to BMN 307 administration 9.Detectable antibodies to the AAV5 capsid at Screening
10.Substance use disorder and/or, active major depressive disorder (as defined by the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders 5th edition ([DSM-5], American Psychiatric Association, 2013) in the past 12 months prior to Screening.
11.Any history of psychosis or bipolar disorder (as defined by DSM-5).
12.Contraindication to use of corticosteroids (CS) or history of condition that could worsen with CS therapy, as assessed and determined by the investigator.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
140 participants
