A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme

Am J Nephrol. 2016;44(2):150-8. doi: 10.1159/000448766. Epub 2016 Aug 17.


Background: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine.

Methods: This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period.

Results: The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD).

Conclusions: In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Bacillus subtilis / enzymology*
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / adverse effects
  • Bacterial Proteins / therapeutic use*
  • Carboxy-Lyases / administration & dosage
  • Carboxy-Lyases / adverse effects
  • Carboxy-Lyases / therapeutic use*
  • Cross-Over Studies
  • Diet / adverse effects
  • Double-Blind Method
  • Female
  • Gastrointestinal Absorption / drug effects
  • Healthy Volunteers
  • Humans
  • Hyperoxaluria / chemically induced
  • Hyperoxaluria / drug therapy*
  • Hyperoxaluria / urine
  • Kidney Calculi / prevention & control*
  • Male
  • Middle Aged
  • Oxalates / metabolism*
  • Oxalates / pharmacology
  • Oxalates / urine
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Renal Elimination


  • Bacterial Proteins
  • Oxalates
  • Recombinant Proteins
  • Carboxy-Lyases
  • oxalate decarboxylase