Proteon Therapeutics, a company developing novel, first-in-class therapeutics to address the medical needs of patients with kidney and vascular diseases, has announced that it will increase the planned enrollment of its ongoing phase 3 PATENCY-2 trial to 600 patients. The increased sample size follows a review of the statistical plan, which revealed a calculation error that overstated the trial’s power for secondary patency, one of the co-primary endpoints. The increased sample size provides 88% power to detect the differences observed in the PATENCY-1 trial with a p-value =0.05 for secondary patency, and 98% power with a p-value =0.05 for fistula use for hemodialysis, the other co-primary endpoint.
The increase in sample size does not alter the study endpoints, which use the same definitions as in the PATENCY-1 trial.
Secondary patency is defined as the length of time from surgical creation until fistula abandonment (final failure). In PATENCY-1, vonapanitase-treated patients experienced a 34% reduction in the risk of secondary patency loss over one year, compared to placebo (p=0.048). At the end of one year, 74% of vonapanitase-treated patients maintained secondary patency, compared to 61% of placebo-treated patients.
Use for hemodialysis is defined as use of the fistula for hemodialysis for at least 90 days or, if hemodialysis was not initiated at least 90 days prior to the patient’s last visit, for at least 30 days prior to the patient’s last visit and in use at the patient’s last visit. In PATENCY-1, 64% of vonapanitase-treated patients used their fistula for hemodialysis, compared to 44% of placebo-treated patients (p=0.006), a 45% relative increase.
With this change in sample size, Proteon expects to complete enrollment in the first quarter of 2018 and to report top-line data in the first quarter of 2019. Proteon still expects to submit a Biologics License Application (BLA) to the US. Food and Drug Administration (FDA) in 2019.
Proteon received written confirmation from the FDA that, if the PATENCY-2 trial is successful in showing statistical significance (p=0.05) on each of the co-primary endpoints, the PATENCY-2 trial together with data from previously completed studies would provide the basis for a BLA submission as a single pivotal study.