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

M
Melissa Lah, MD

Primary Investigator

Administratively Closed
15 years - 100 years
All
Phase N/A
5 participants needed
2 Locations

Brief description of study

BMN 307 is an experimental drug that is being evaluated for the treatment of patients with phenylketonuria (PKU). The purpose of this study is to find the best dose of BMN 307 and to learn the effects (good and bad) this drug has on people with PKU.

Detailed description of study

Participants will complete physical exams, a liver ultrasound and optional biopsy, ECG, diet diary, vaccines/titers, brain function tests, breath tests, interview, and questionnaires throughout the study. Participants will also provide blood, urine, stool, saliva, and semen samples throughout the study.
Participants will take steroids by mouth daily for 16 weeks prior to starting the study drug. BMN 307 will be infused over a 1-5 hour period at the clinic, and participants will remain in the clinic for 8 hours following infusion. Participants will then complete follow-up visits weekly for 16 weeks, every 2 weeks for weeks 16-24, every 4 weeks for weeks 24-96, every 12 weeks for weeks 96-120, every 24 weeks for weeks 120-240, and a final visit at week 260.
Participants will receive a stipend of $100 per study visit (a maximum of $5,000 if all visits are completed) in addition to reimbursement for reasonable travel costs and expenses incurred for each study visit completed. 

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: 2002122874, Phenylketonuria, PKU
  • Age: 15 years - 100 years
  • Gender: All

Age
1. Part A: age 18 years and older at Screening
2. Part B: age 15 years and older at Screening (as allowed per local HA and EC/IRB)
 
Type of Participant and Disease Characteristics
3. Diagnosis of PKU which is a condition characterized by PAH deficiency
4. Average of two plasma Phe levels > 600 μmol/L during the Screening period
5. 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:
o Last dose of pegvaliase or large neutral amino acids (LNAAs) must have been at least 30 days prior to Screening
o Last dose of sapropterin must have been at least 7 days prior to Screening
6. Ability and willingness to maintain dietary protein intake consistent with baseline intake for the duration of the study unless otherwise directed.
7. Willingness to abstain from alcohol, herbal and natural remedies, dietary supplements, and hepatotoxic medications from Screening through at least 52 weeks post-BMN 307 administration
8. Ability to maintain stable doses of medication for ADHD, depression, anxiety, or other psychiatric disorders for ≥ 8 weeks prior to Screening. Subjects must also be willing to maintain stable doses of these medications during Screening and throughout the study, unless change is medically indicated
9. Willingness to avoid donation of semen until 3 consecutive semen samples are negative for vector DNA.
10. Willingness to avoid donation of blood until 3 consecutive blood samples are negative for vector DNA.
11. Willingness to avoid donation of organs or tissue until 3 consecutive negative vector DNA samples in all collected matrices (refer to Section 8.4.7).
12. Willingness and capable per investigator opinion to comply with study procedures and requirements
13. Up to date with the following vaccinations at Screening:
o S. Pneumoniae with pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23). Subjects who never received vaccinations against these pathogens (or with uncertain vaccination history against these pathogens) must be willing to receive administration of PCV13 during the screening period and PPSV23 during the study. PCV13 and PPSV23 are not required for subjects with known contraindication (refer to Table 1.3.1 and Section 6.5.1).
o Influenza virus. Subjects without documentation of receipt of influenza vaccination for the current influenza season will be administered influenza vaccine during the screening period. If influenza vaccine for current season is not available or not indicated at time of Screening, the subject will receive the vaccination when seasonally appropriate. The influenza vaccine is not required for subjects with known contraindication (refer to Table 1.3.1 and Section 6.5.1).
Subjects receiving one or more of these vaccinations must have at least 2 weeks between the date of the last vaccination and the date of BMN 307 infusion (ie, Day 1).
 
Sex
14. Males and females are eligible to participate in this clinical study
15. Sexually active male subjects must agree to use an acceptable method of effective contraception for at least 12 weeks post-BMN 307 administration (refer to Appendix 5, Section 10.5). After 12 weeks, subjects may stop contraception use only if they have had 3 consecutive semen samples with no detectable viral vector DNA
16. 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 (refer to Appendix 5, Section 10.5).
17. Not breastfeeding at Screening, and not planning to become pregnant (self or partner) or breastfeed during required period of contraception (refer to Appendix 5, Section 10.5).
 
Informed Consent
18. Subjects must be capable of giving signed informed consent as described in Appendix 1, Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
 
19. Parent(s) or guardian(s), for subject less than the age of majority, must be willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects under the age of majority must be willing and able to provide written assent (if required by local HA or the EC/IRB) after the nature of the study has been explained and prior to performance of any research-related procedure.
 
Optional Liver Biopsy 
Subjects ≥ 18 years of age able to sign informed consent and comply with requirements for the optional liver biopsy.

Updated on 13 Nov 2025. Study ID: MMGE-BIOMARIN-307-201, 2002122874, TX11334

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