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Abstract: INFO06

Establishing Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria (URIROX-2)

Session Information

Category: Bone and Mineral Metabolism

  • No subcategory defined

Authors

  • Kausz, Annamaria T., Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Weeks, Alicia, Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Tasian, Gregory Edward, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Scales, Charles D., Duke Clinical Research Institute, Durham, North Carolina, United States
Description

Hyperoxaluria is a major risk factor for calcium oxalate kidney stones (KS), and can also lead to chronic kidney disease. Enteric hyperoxaluria (EH) refers to increased urinary oxalate (UOx) excretion caused by fat malabsorption due to surgery or an underlying medical disorder. There are no approved therapies for EH.

Reloxaliase, a first-in-class oral enzyme therapy that decreases systemic oxalate absorption and in turn, UOx excretion by degrading oxalate within the GI tract, is in development to treat EH. Results of URIROX-1, the first Phase 3 study, and COVID-19, led to streamlining of the second pivotal Phase 3 study, URIROX-2. Notably, a higher than expected KS event rate in URIROX-1 reduced the sample size required to accrue enough KS events to enable demonstration of a meaningful reduction in KS disease progression.

URIROX-2 is double-blind, randomized placebo-controlled trial recruiting 200 subjects ≥18 years with EH and KS, eGFR ≥30 mL/min/1.73m2 and UOx ≥50 mg/d. Subjects will be randomized to reloxaliase (7,500 u) or placebo, dosed orally 3-5x/d, for a minimum of 2 years.

Primary endpoints are percent change from baseline in 24-h UOx during weeks 1-4, and KS disease progression, defined as a composite based on clinical events, procedures, or new KS or KS growth on serial imaging (KUB/US, and CT). Resource utilization for KS management, eGFR, and quality of life will be also be assessed. Many study visits may now be performed remotely with 24-h urine collections processed by visiting nurses, ensuring data capture continuity.

The adaptive design elements, including two conditional probability-based sample size reassessments, were incorporated to maximize trial efficiency and ensure success in achieving the UOx primary endpoint to support accelerated approval, and KS disease progression to confirm clinical benefit.

URIROX-2, the largest RCT to date in EH, will establish the effect of reloxaliase on 24-h UOx and KS disease progression, and will also provide valuable information regarding the natural history of EH and its impact on patients and healthcare resource utilization.

This international trial (ClinicalTrials.gov NCT03846090) is currently enrolling subjects. For information on becoming a clinical trial site, email: clinical302@allenapharma.com.

Funding

  • Allena Pharmaceuticals