Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria

A multi-center, open-label, single arm study to evaluate the safety and the effect of ALLN-177 to reduce urinary oxalate excretion in recurrent kidney stone formers with associated hyperoxaluria. The study design includes a screening period to confirm eligibility, followed by a 3-day baseline period, 4-day open label treatment period with ALLN-177 and 4-day follow up period.

• ALLN-177 (Drug), also known as Oxalate degrading enzyme, Oxalate decarboxylase: ALLN-177 is orally administered oxalate decarboxylase (OxDc). The goal of oral therapy with ALLN-177 is to enzymatically degrade both dietary oxalate and endogenously produced oxalate secreted in the gastrointestinal tract resulting in decreased absorption and reduced urinary oxalate excretion.

Primary outcomes

• Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion [7 days]: Change from Baseline is defined as Baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7).

Secondary outcomes

• Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion [7 days]: Percent Change from Baseline is defined as baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7) divided by baseline value times 100%

Sex: All

Inclusion Criteria:

* Able to provide informed consent
* Able to comply with study procedures
* History of enteric or idiopathic hyperoxaluria and at least one calcium oxalate kidney stone
* Hyperoxaluria >36mg of oxalate/24-hr
* May be taking drugs for the prevention of stone disease as long as there have been no changes in these medications for at least 3 months

Exclusion Criteria:

* Uric acid ≥1.5g/24-hr
* Estimated glomerular filtration rate of < 60 mL/min
* Positive results from drug urine screen
* Requires daily vitamin C (defined as >10 days of >300 mg/day)
* Diagnosis of 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.
* Auto-immune disorder requiring high dose steroids or other immunosuppressant drugs.
* Subjects who are pregnant. Women of childbearing potential must have a negative pregnancy test prior to enrollment and must practice approved methods of birth control during the trial
* History of cancer diagnosis except for within the past 5 years excluding dermal squamous and/or basal cell carcinoma or cervical carcinoma in situ.
* Taken investigational compound within 30 days prior to the first day of the study
* Treatment with cholestyramine
* Average daily dietary intake of <75 mg oxalate per day calculated from diet recalls

Participant flow

Outcome results

• Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion (Primary), Mean, mg/day: ALLN-177 -13.92 +/- 18.37
• Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion (Secondary), Mean, percentage change: ALLN-177 -13.28 +/- 16.62

Adverse events

Time frame: Up to 11 days.

Other adverse events by term

• Results publication: Lingeman JE, Pareek G, Easter L, Pease R, Grujic D, Brettman L, Langman CB. ALLN-177, oral enzyme therapy for hyperoxaluria. Int Urol Nephrol. 2019 Apr;51(4):601-608. doi: 10.1007/s11255-019-02098-1. Epub 2019 Feb 19. PMID 30783888

• Lee Brettman, MD, FACP, Study director, Medical Director