Background

Do you have a patient with a history of hyperoxaluria due to an underlying malabsorptive gastrointestinal condition (e.g., bariatric surgery, Crohn’s disease, short bowel syndrome, or other malabsorption disorders)?



If YES, your patient may be eligible for the uriROX-2 clinical research study.

Enteric
Hyperoxaluria
Overview

Enteric HOx refers to excessive excretion of oxalate in the urine that is a metabolic complication of increased gastrointestinal (GI) oxalate absorption. Enteric HOx is most commonly a complication of bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB), and can also be a consequence of inflammatory bowel diseases (IBDs) with small bowel involvement, such as Crohn’s disease or other conditions associated with GI malabsorption, including cystic fibrosis (and other conditions associated with pancreatic insufficiency) or short bowel syndrome following ileal resection for any reason. 1
The mechanisms potentially contributing to excessive GI absorption of oxalate and subsequent HOx in these settings include fat malabsorption (unabsorbed fat and bile acids react with calcium in the intestinal lumen, limiting the amount of calcium that can bind oxalate, leaving more free oxalate to be absorbed) and increased concentration of fatty acid and bile salts causing increased GI permeability.2 This is illustrated by one study using radiolabeled oxalate, which reported that subjects who had undergone jejunoileal bypass had substantially increased oxalate absorption, with 36.8% of the isotope detected in their urine, compared with 14.4% in idiopathic stone formers and 13.6% in normal controls. 3

There is an extensive epidemiologic literature describing enteric HOx, some reporting severe HOx. In bariatric surgery patients who have had a kidney stone, UOx excretion frequently exceeds 80 mg/24 hr, and some subjects may even have > 150 mg/24 hr. 4 Other disease states that lead to fat malabsorption, such as pancreatic insufficiency, cystic fibrosis, and small bowel resection, can also result in pronounced HOx. 5

In post-bariatric surgery patients and patients with other malabsorptive conditions, HOx is a well-described cause of nephrolithiasis and nephrocalcinosis. 6 In addition, enteric HOx is increasingly recognized as contributing to chronic kidney disease (CKD) and ESRD as a consequence of oxalate nephropathy. 7

A number of studies have identified higher UOx as a significant factor associated with kidney stones after bariatric surgery. 8
There is no approved pharmacologic therapy specifically directed at reducing the absorption of oxalate from the GI tract. Current management consists of recommendations to reduce dietary oxalate intake and increase calcium intake, and drink large volumes of fluid. These recommendations are aimed at decreasing oxalate absorbed from food and decreasing urinary CaOx crystalluria, to minimize the risk of subsequent kidney stone formation and/or oxalate nephropathy due to CaOx crystals.9 However, many subjects with enteric HOx may be unable to consistently ingest the quantities of fluid required to maintain adequate urine volume. Furthermore, recommendations for a low-oxalate diet are somewhat in conflict with general recommendations that patients follow a healthy diet composed of largely plant-based foods, as many plants are high in oxalate. In conclusion, there remains a significant unmet need for improved management of patients with enteric HOx.
Background

If you are interested in referring a patient to this important research effort or would like to speak with a member of the study team to learn more information about the uriROX‑2 study, please contact us.


uriROX‑2 Overview

Allena is committed to researching safe and effective treatments for patients with rare and severe metabolic and kidney disorders, including enteric hyperoxaluria.

Background
Protocol Title

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)

Protocol Number

ALLN-177-302

Phase of Development

Phase III

ClinicalTrials.gov Identifier

NCT03847090

Study Treatment

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.

Key Objectives
1

Evaluate the efficacy of reloxaliase in reducing UOx excretion in subjects with enteric HOx

2

Evaluate the long-term safety of reloxaliase

3

Evaluate the long-term effect of treatment with reloxaliase on kidney stone disease progression and kidney function

4

Assess impact of treatment with reloxaliase on burden of illness (kidney stone associated 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, please complete our contact form.
  • Is the patient 18 years of age or older?

  • Does the patient have an underlying enteric disorder associated with malabsorption? Examples could include malabsorptive bariatric surgery (e.g., Roux-en-Y gastric bypass, jejunoileal bypass, biliopancreatic diversion) a minimum of 12 months prior to screening, short bowel syndrome, inflammatory bowel disease with small bowel involvement, cystic fibrosis, pancreatic insufficiency, or celiac disease.

    • Note: Patients who have had restrictive-only bariatric procedures (e.g., vertical banded gastroplasty, adjustable gastric banding, sleeve gastrectomy) are not eligible.

    • Patients with a current ileostomy or a total colectomy are not eligible.

  • 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?

  • 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 a recent kidney stone was determined to be due to an infection (e.g., struvite stone, recurrent urinary tract infections), medications associated with crystalluria (e.g., carbonic anhydrase inhibitors [acetazolamide, topiramate], triamterene, protease inhibitors, guaifenesin, ephedrine, sulfonamides), or medications known to cause fat malabsorption (e.g., orlistat)?

  • 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 dose regimens of steroids or other immunosuppressant drugs, including transplant recipients, are NOT excluded.

Background

If you are interested in referring a patient to this important research effort or would like to speak with a member of the study team to learn more information about the uriROX‑2 study, please contact us.