BP41674_A study of RO7248824 in Angelman Syndrome patients (TANGELO)

• Research type

  Research Study

• Full title

  AN OPEN-LABEL, MULTICENTER STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF RO7248824 IN PARTICIPANTS WITH ANGELMAN SYNDROME

• IRAS ID

  280387

• Contact name

  Professor Helen Cross

• Contact email

  helen.cross@gosh.nhs.uk, h.cross@UCL.ac.uk

• Sponsor organisation

  F. Hoffmann-La Roche

• Eudract number

  2019-003787-48

• Duration of Study in the UK

  2 years, 10 months, days

• Research summary

  Angelman Syndrome (AS) is caused by various genetic defects leading to absence of functional Ubiquitin Protein Ligase E3A (UBE3A) protein selectively in neuronal cells, which results in severe physical and learning disabilities. In neuronal cells of unaffected individuals, the maternally-inherited UBE3A allele is the only source of UBE3A protein because the paternal UBE3A allele is silenced. In individuals with AS, the maternal UBE3A allele is not functional and therefore UBE3A is not generally expressed in neurons.
  There is a high unmet medical need in AS patients as there are no approved treatments for AS and no clear guidelines for symptom-based interventions in this population. Currently available treatments are symptomatic and largely limited to improvement of seizures and reduction of sleep disturbances. Insight into the mechanism of action of the disease, however, has suggested a path forward for disease-modifying therapies.
  RO7248824 aims to unsilence expression of the paternal gene and enable UBE3A protein production in neurons in AS according to the mechanism described above.
  The primary objective of this study is to assess the safety and tolerability profile of RO7248824 and the secondary to investigate the plasma pharmacokinetics (PK).
  This is a Phase I multicenter, non-randomized, adaptive, open label, multiple ascending, intra-participant dose-escalation study using intrathecal (IT) administration participants with (AS) aged 1-12 years.
  Each participant will receive up to three IT injections of varying dose levels over a period of 8 weeks, with a minimum of approximately 4 weeks between each dose administration. The total duration of the study will be up to 58 weeks.
  There will be approximately 66 patients recruited Globally of which 4 in the 2 UK sites
  The study is sponsored by F. Hoffman La Roche
  

• REC name

  North West - Greater Manchester Central Research Ethics Committee

• REC reference

  20/NW/0210

• Date of REC Opinion

  11 Jun 2020

• REC opinion

  Further Information Favourable Opinion