Abstract: TH-PO788

Phase 2 Open Label Single Arm Repeat Dose Study to Assess the Effect of SNF472 on Wound Healing in Uraemic Calciphylaxis Patients

Session Information

Category: Dialysis

  • 607 Dialysis: Epidemiology, Outcomes, Clinical Trials - Non-Cardiovascular

Authors

  • Brandenburg, Vincent, University Hospital Aachen, Herzogenrath, NW, Germany
  • Sinha, Smeeta, Salford Royal NHS Foundation Trust, Salford, United Kingdom
  • Torregrosa, Jose-Vicente, Hospital Clínic de Barcelona, Barcelona, Spain
  • Salcedo, Carolina, Sanifit, Palma, Spain
  • Klassen, Preston, Sanifit, Palma, Spain
  • Garg, Rekha, Sanifit, Palma, Spain
  • Joubert, Pieter H., Sanifit, Palma, Spain
  • Perelló, Joan, Sanifit, Palma, Spain
Background

SNF472, an intravenous (i.v.) formulation of myo-inositol hexaphosphate, is being developed for treating calciphylaxis (CUA) in patients with end-stage renal disease on hemodialysis (HD). It selectively inhibits the final common pathway in the etiology of vascular calcification, the formation and growth of hydroxyapatite crystals.

Methods

An open label, single arm trial investigating the effect of SNF472 on top of standard of care in the treatment of CUA in HD patients. Inclusion criteria was a new diagnosis of CUA or a recurrence of CUA after a period of at least 90 days without evidence of active CUA-related skin lesions. Patients are treated for 12 weeks with i.v. 6-9 mg/kg of SNF472 three times per week during each dialysis session. The endpoints are lesion score based on the Bates-Jensen Wound Assessment tool (BWAT; primary endpoint), pain assessed by Visual Analog Pain Scale (VAS) and a validated wound-associated quality of life (QoL) questionnaire. The BWAT and VAS are assessed every 2 weeks; wound-QoL is assessed at baseline, week 6 and week 12.

Results

The study has enrolled 12 patients with 9 completing the 12-week treatment, and 2 discontinued early due to death (not related to study drug) and 1 withdrew consent. Data from 9 completers shows a statistically significant reduction in BWAT score by week 10 which continued to week 12. Similarly, there was a statistically significant reduction in mean pain VAS score by week 8 and week 12. An increase in pain is noted one week after ending SNF472 treatment, strengthening the likelihood of a causal impact on pain. SNF472 has a statistically significant improvement on global wound-QoL, by week 12. Similarly, the 3 subscales of the global wound QoL scale all show improvements by week 12. There were 14 serious adverse events and 2 deaths, and none were related to SNF472 as per investigator.

Conclusion

These results suggest that SNF472 has a consistent benefit across multiple parameters and is well tolerated in patients with CUA. Thus, SNF472 has the potential to treat CUA, a rare and serious disease with a high mortality rate and no approved treatment.

Funding

  • Commercial Support