PHYOX: Phase 1 Clinical Development Program

PHYOX: Phase 1 Clinical Development Program


In order to speed the drug development process, Dicerna developed a novel clinical trial design: the PHYOX study (also known as DCR-PHXC-101) was a Phase 1 single-ascending dose study in normal healthy volunteers (NHVs) and patients with primary hyperoxaluria (PH). This clinical trial design was selected to rapidly advance DCR-PHXC as Dicerna works to develop a therapy for PH.

The study was divided into two groups:

  • Group A was a placebo-controlled, single-blind, single-center Phase 1 study in NHVs
  • Group B was an open-label, multi-center study in patients with PH type 1 (PH1) and PH type 2 (PH2)

We initiated the PHYOX trial in NHVs in the fourth quarter of 2017 and dosed the first patient with PH in May 2018.

The primary objective of the PHYOX trial (ClinicalTrials.gov: NCT03392896) is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses of DCR-PHXC. Secondary endpoints include the change in 24-hour urinary oxalate excretion from baseline, defined as the mean of two 24-hour collections during screening.

Proof-of-Concept Data

In the second half of 2018, Dicerna announced the presentation of late-breaking data from its ongoing PHYOX Phase 1 trial, in a poster presented at the American Society of Nephrology (ASN) Annual Kidney Week 2018. DCR-PHXC, the Company’s lead GalXC™ product candidate, was associated with normalization or near-normalization of urinary oxalate levels in a majority of adult patients with PH1 and PH2 following single-dose administration. Investigators reported that:

  • A single 3.0-mg/kg dose of DCR-PHXC brought urinary oxalate levels into the normal range (defined as 24-hour excretion ≤0.46 mmol) at one or more post-dose time points in three of four participants, including a mean maximal reduction in 24-hour urinary oxalate of 65%.
  • A single 1.5-mg/kg dose led to near-normalization (defined as 24-hour excretion <0.6 and ≥0.46 mmol) in three of four PH1 participants and led to a mean maximal reduction in urinary oxalate of 50% in the five patients dosed at that level, including one PH2 patient.
  • All patients demonstrated a clinically significant reduction in urinary oxalate (defined as >30% reduction compared to baseline).
  • Based on a data cut of October 1, 2018, DCR-PHXC is safe and well-tolerated in this ongoing study, based on data from 12 adult participants with PH1 (n=11) and PH2 (n=1) and 25 adult normal healthy volunteers (NHVs).

The observed reduction in 24-hour urinary oxalate following a single dose of DCR-PHXC in both PH1 and PH2 participants is a promising sign of this compound’s potential potency and duration of action.

The Future of PHYOX

The next step in the development process for DCR-PHXC is a multi-dose Phase 2/3 registration trial, which the Company is on track to initiate in the first quarter of 2019. More information about the clinical trial and study design will be forthcoming.