Abstract: TH-PO1073
Results of a Phase 2 RCT of ALLN-177 in Patients with Secondary Hyperoxaluria
Session Information
- Mineral Disease: Nephrolithiasis
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Mineral Disease
- 1204 Mineral Disease: Nephrolithiasis
Authors
- Nigwekar, Sagar U., Massachusetts General Hospital , Boston, Massachusetts, United States
- Lingeman, James E., IU Health Physicians Urology, Indianapolis, Indiana, United States
- Bolognese, James A, Cytel inc, Cambridge, Massachusetts, United States
- Kausz, Annamaria T., Allena Pharmaceuticals, Newton, Massachusetts, United States
Background
Hyperoxaluria (HOx) is a metabolic disorder associated with increased risk of nephrolithiasis and other sequelae including oxalate nephropathy. Secondary HOx is caused by excess oxalate absorption from diet due to enteric disorders (enteric HOx, EH) or is unexplained (idiopathic). There are no approved pharmacotherapies for HOx. To address this unmet need, ALLN-177 was developed as a novel oral formulation of crystalline oxalate decarboxylase, an oxalate-specific enzyme that degrades oxalate in the gastrointestinal (GI) tract, thereby reducing urine oxalate (UOx).
Methods
This double-blind, placebo-controlled RCT randomized adult subjects with secondary HOx and UOx ≥50 mg/d 1:1 to ALLN-177 (7500 u/meal) or placebo taken orally with meals 3x/day for 28 days. Multiple 24-hr urine collections were obtained to determine change in UOx, and the primary analysis used a mixed effects repeated measures analysis of variance model.
Results
67 subjects were randomized and treated (32 ALLN-177, 35 placebo); 18 had EH. The primary endpoint (EP) 24-hr UOx change from baseline to Week (Wk) 4 showed a trend favoring ALLN-177 (-5.4 mg/d; see Table). Key secondary EP were statistically significant, and a substantially greater, clinically meaningful treatment effect was seen in post-hoc analyses in the predefined EH subset, including the time-weighted average (TWA) assessing the aggregate effect across the study duration.
Adverse events were reported by 50% of ALLN-177 subjects vs. 63% placebo, and GI AEs were the most frequently reported, 16% ALLN-177 vs 40% placebo. No subjects discontinued ALLN-177 for any reason.
Conclusion
ALLN-177 was well-tolerated and has potential to meaningfully reduce UOx in patients with EH, who have a substantially increased risk for renal complications and thus an unmet need for an effective therapy to reduce UOx.
| Endpoints | All | Enteric |
| Comparison vs. Placebo mean (90% CI) | Comparison vs. Placebo mean (90% CI) | |
| Least squares mean change in UOx to Wk4 – mg/d | -5.4 (-14.05, 3.16) | -15.4 (-46.31, 15.62) |
| Change in TWA UOx (Wks1-4) – mg/d | -6.7 (-13.03, -0.30) | -23.1 (-43.95, -2.15) |
| % change in UOx to Wk4 | -13.18% (-24.66, -1.71) | -35.3% (-70.19, -0.41) |
Funding
- Commercial Support –