Evaluate the Effect of ALLN-177 in Reducing Urinary Oxalate in Patients With Hyperoxaluria and Kidney Stones

This is a multicenter, randomized, double-blind, placebo controlled study to evaluate the efficacy of ALLN 177 compared with placebo in reducing the urinary excretion of oxalate in subjects with secondary hyperoxaluria and kidney stones. ALLN-177 is an orally administered form of oxalate decarboxylase. The goal of therapy with ALLN-177 is to reduce urinary oxalate excretion by decreasing the absorption of oxalate from the gastrointestinal tract.

Eligible subjects will be randomized to 7 days of treatment with a dose ALLN-177 or placebo and following a washout period, crossed over to an alternate treatment. Urinary oxalate excretion will be assessed by 24-hr urine collections throughout the study.

The study allows for up to 60 subjects.

• ALLN-177 low dose (Drug), also known as Oxalate decarboxylase: ALLN-177 1,500 units (1 capsule)/meal PO 3 times per day
• ALLN-177 mid dose (Drug), also known as Oxalate decarboxylase: ALLN-177 3,000 units (2 capsules)/meal PO 3 times per day
• ALLN-177 high dose (Drug), also known as Oxalate decarboxylase: ALLN-177 7,500 units (5 capsules)/meal PO 3 times per day
• Placebo (Drug): Placebo: 1, 2 or 5 capsules with meals PO 3 times per day

Primary outcomes

• Mean urinary oxalate excretion (mg/24 h) following treatment [on 7 days of treatment]

Secondary outcomes

• Change from baseline in mean urinary oxalate excretion (mg/24 h) [on 7 days of treatment]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* History of enteric or idiopathic hyperoxaluria and at least one kidney stone within the past 2 years
* Hyperoxaluria at screening
* May be taking drugs for the prevention of stone disease

Exclusion Criteria:

* Hyperuricosuria
* Glomerular filtration rate < 55 mL/min/1.73m2
* Hypercalcemia or hypothyroidism
* Obstructive uropathy, chronic urosepsis, renal failure, renal tubular acidosis, primary hyperparathyroidism, primary hyperoxaluria, pure uric acid and cystine stones, and/or medullary sponge kidney
* Treatment with cholestyramine
* Average daily dietary intake of oxalate <75 mg per day

• Annamaria Kausz, MD MS, Study director, VP Clinical Development