Open-Label, Dose Escalation study of BMN 307 in Phenylketonuria

• Research type

  Research Study

• Full title

  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 and Plasma Phe Levels > 600 μmol/L

• IRAS ID

  272289

• Contact name

  Robin Lachmann

• Contact email

  robin.lachmann@uclh.nhs.uk

• Sponsor organisation

  BioMarin Pharmaceutical Inc.

• Eudract number

  2019-001878-28

• Duration of Study in the UK

  7 years, 10 months, 1 days

• Research summary

  Phenylketonuria (PKU) is a rare inherited disorder which affects the body's ability to break down the amino acid (a
  building block of protein) phenylalanine (Phe). If the disease is uncontrolled, elevated levels of Phe in the blood are
  toxic to the brain and can cause brain damage. PKU patients can experience symptoms such as poor sustained
  attention and a variety of behavioural and psychiatric problems including depression and anxiety, and a negative
  overall effect on quality of life. Current treatment involves a protein-restricted diet to control the level of Phe in the blood, however poor compliance rates to this diet are often demonstrated particularly amongst the adolescent.

  Studies suggest that the maintenance of low blood Phe through life is important in order to provide optimal brain
  function.

  302-201 is an open-label study to establish dose (Part A) and assess the safety and effectiveness (Part B) of BMN 307. BMN 307 is an Adeno-Associated Virus (AAV) Vector-Mediated gene transfer of Human Phenylalanine Hydroxylase (PAH). Based on non-clinical data in a mouse model, it is anticipated that a single dose of BMN 307 will result in restoration of normal Phe metabolism with rapid plasma Phe reduction.

  Approximately 78 patients will take part in this study globally (≥ 18 years for Part A and ≥ 15 years for Part B)
  
  Participants will be required to fast before certain visits, have blood tests, physical exams, liver assessments, keep a food diary, provide urine, stool, saliva and semen samples, perform a series of neurocognitive tests, and complete questionnaires and interviews to assess their disease over a 260 week period. Participants will also have the option to have a liver biopsy assess the effect of BMN 307 on the liver.

• REC name

  North East - York Research Ethics Committee

• REC reference

  19/NE/0325

• Date of REC Opinion

  13 Dec 2019

• REC opinion

  Further Information Favourable Opinion