Abstract: INFO16-SA
Establishing Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria (URIROX-2)
Session Information
- Informational Posters - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- No subcategory defined
Authors
- Kausz, Annamaria T., Allena Pharmaceuticals, Newton, Massachusetts, United States
- Curhan, Gary C., Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Tasian, Gregory Edward, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Scales, Charles D., Duke University, Durham, North Carolina, United States
Description
Hyperoxaluria (HOx) is a major risk factor for calcium oxalate kidney stones, which can lead to chronic kidney disease and end-stage kidney disease. Enteric hyperoxaluria (EH) refers to increased urinary oxalate (UOx) excretion as a complication of fat malabsorption due to GI surgery or other diverse gastrointestinal conditions. There are no approved therapies for EH; current recommendations include reducing dietary oxalate and increasing calcium and fluid intake, calcium/citrate supplements, and thiazides, but these may be difficult to sustain and of limited effectiveness.
Reloxaliase (ALLN-177) is a first-in-class oral enzyme therapy that achieves its therapeutic effect by degrading oxalate in the GI tract, resulting in less oxalate absorption and lower urinary oxalate (UOx) excretion.
The current trial (URIROX-2) is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of reloxaliase in patients with EH. The study is recruiting 400 subjects ≥18 years of age with a history of EH and at least one kidney stone, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2and baseline 24-hr UOx ≥50 mg/24hr. Subjects will be randomized to reloxaliase (7,500 units) or placebo, orally with each meal or snack(3-5x/day) and followed for a minimum of 2 years and up to 5 years. The primary endpoints are percent change from baseline in 24-hour UOx in weeks 1-4 and, in long-term follow-up, kidney-disease progression. Kidney stone progression will be assessed clinically as well as with serial imaging using KUB, ultrasound, and CT. Resource utilization for management of kidney stones, change in eGFR and quality of life (QoL) will also be assessed.
This is the largest RCT ever conducted in EH, and is designed to establish the effect of reloxaliase on 24-hour UOx excretion and kidney stone disease progression, provide valuable information regarding the natural history of disease on the basis of clinical, biological, radiographic and QoL endpoints.
This international trial is registered on ClinicalTrials.gov (NCT03846090) (funded by Allena Pharmaceuticals) is currently enrolling subjects. Information on becoming a clinical trial site can be obtained by calling (617) 467-4577 x398 or by email: clinical302@allenapharma.com
Funding
- Allena Pharmaceuticals