Evaluation of the Efficacy and Safety of VX-864 in Subjects With the PiZZ Genotype

• Research type

  Research Study

• Full title

  A Phase 2, Open-label Study Evaluating Efficacy and Safety of VX-864 in Subjects With Alpha-1 Antitrypsin Deficiency Who Have the PiZZ Genotype, Over 48 Weeks

• IRAS ID

  1006714

• Contact name

  N/A N/A

• Contact email

  medicalinfo@vrtx.com

• Sponsor organisation

  Vertex Pharmaceuticals Incorporated

• Eudract number

  2022-002746-40

• Clinicaltrials.gov Identifier

  NCT05643495

• Research summary

  Research Summary
  Alpha-1 antitrypsin deficiency (AATD) is an inheritable genetic disorder involving a protein folding defect causing low circulating levels of alpha-1 antitrypsin (AAT). AAT is produced primarily in the liver and secreted into the blood to the lungs to protect the lungs from damage.
  A change in the AAT protein results in misfolding of the protein known as the Z-AAT protein (PiZZ) the Z protein produced is abnormal and gets trapped in the liver and cannot reach the circulation. The deficiency of circulating AAT can result in the increase risk of development of chronic lung condition. The build up of PIZZ genotype may cause liver damage.
  The purpose of this study is to investigate the effect and safety of VX-864 (investigational study drug) on blood levels of functional AAT in individuals with the PiZZ genotype.
  Approximately 20 subjects with the PiZZ genotype will be enrolled: Groups A and B will enroll approximately 10 subjects each. All subjects will receive VX-864 500 mg every 12 hours (q12h) for 48 weeks. Group A subjects will not have a liver biopsy. Subjects in Group B will have 2 liver biopsies performed over the course of the study.

  Summary of Results
  Lay Summary Results for VX22-864-108, A Study to Evaluate Efficacy and Safety of VX-864 in Participants With the PiZZ Genotype This study involved participants who have Alpha-1 Antitrypsin Deficiency who also have the PiZZ Genotype. It took place at 13 locations in 4 countries: Germany, Ireland, the UK and the United States. 14 people took part in this study. The study had 2 parts. In Part A participants got VX-864 twice a day for 48 weeks. In Part B participants had a small sample of their liver taken for testing and then received VX-848 twice a day for 48 weeks. They had another small sample of their liver taken for testing either half way through (24 weeks) or at the end of the study (48 weeks). The testing to see how well the study drug worked were stopped early because the sponsor decided to end them. Because of this, the results about how well the drug worked were not finished. For more information, detailed results are publicly available at www.clinicaltrials.gov, search NCT05643495 or VX22-864-108.

• REC name

  Wales REC 2

• REC reference

  22/WA/0346

• Date of REC Opinion

  21 Jun 2023

• REC opinion

  Further Information Favourable Opinion