Establishing the Safety and Efficacy of Reloxaliase (Oxalate Decarboxylase) in Patients with Enteric Hyperoxaluria: A Phase III Randomized, Double-Blind, Placebo-Controlled Study (uriROX-2)
Phase of Development
Reloxaliase (ALLN-177) is a crystalline formulation of B. subtilis oxalate decarboxylase, an oxalate-degrading enzyme expressed in E. coli, which degrades oxalate to formate and carbon dioxide. Once the capsule is taken (orally) with food, reloxaliase degrades dietary oxalate, resulting in decreased oxalate available for absorption into systemic circulation and subsequently reduced urinary oxalate (UOx) excretion.
The safety and effectiveness of reloxaliase are being tested against placebo, a capsule that looks the same as reloxaliase but does not have active ingredients.
Determine the efficacy effect of reloxaliase in reducing UOx excretion in subjects with enteric HOx
Evaluate the long-term safety of reloxaliase
Evaluate the long-term effect of treatment with reloxaliase on kidney stone disease progression and kidney function
Assess impact of treatment with reloxaliase on burden of illness (kidney stone associate healthcare resource utilization
Key Eligibility Criteria
If your patient’s status is "yes" to the following questions, it is a good indicator that he or she may be eligible for the study. If you determine that the patient may be eligible, contact a study site.
• Is the patient 18 years of age or older?
• Does the patient have an underlying enteric disorder associated with malabsorption? Examples could include Roux-en-Y gastric bypass, jejunoileal bypass, biliopancreatic diversion, short bowel syndrome, inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency, or celiac disease.
• Does the patient have a known or suspected history of HOx (e.g., history of kidney stones or oxalate nephropathy)?
• Does the patient have at least 1 documented kidney stone (spontaneous kidney stone passage or intervention to remove kidney stone, or new or enlarged stone on imaging) within 2 years prior to screening? AND Does the patient have at least 4 weeks elapsed since the last episode of symptomatic nephrolithiasis and/or intervention for kidney stone removal?
• For patients taking concomitant medication for management of kidney stone risk factors (e.g., thiazides, calcium supplements, alkali therapy, allopurinol): has the patient been on a stable dose regimen for ≥8 weeks prior to screening, and with no changes in dosing (dose level or dosing frequency) anticipated during the first 24 weeks of the study treatment period?
If your patient’s status is "yes" to the following questions, it is a good indicator that he or she may NOT be eligible for the study.
• Does the patient have a known genetic, congenital, or other cause of kidney stones (e.g., primary hyperoxaluria, primary hyperparathyroidism, medullary sponge kidney), OR recent kidney stone was determined to be due to an infection (e.g., struvite stone, recurrent urinary tract infections) or medications associated with crystalluria (e.g., carbonic anhydrase inhibitors [acetazolamide, topiramate], triamterene, protease inhibitors, guaifenesin, ephedrine, sulfonamides)?Is the patient unable or unwilling to discontinue Vitamin C supplementation at Screening and for the duration of the study?
• Has the patient had any malignancy or treatment for malignancy within 12 months prior to Screening with the exception of localized basal cell or squamous cell skin cancer or any cancer in situ?
• Note: Patients in remission and on a stable dose of chronic suppressive or maintenance therapy are NOT excluded.
• Does the patient have an active autoimmune disorder or other condition requiring therapy with high doses of systemic steroids (i.e., >10 mg/day prednisone or equivalent) or intensification of other immunosuppressant therapy within 4 weeks prior to Screening?
• Note: Stable patients on low chronic or maintenance doses of steroids or other immunosuppressant drugs, including transplant recipients, are NOT excluded.