Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria (URIROX-2)

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)

The purpose of this study is to determine the efficacy, durability and long-term safety of reloxaliase in patients with enteric hyperoxaluria.

Study Overview

• Status: Terminated
• Conditions: Enteric Hyperoxaluria
• Intervention / Treatment: Drug: Reloxaliase; Drug: Placebo

Detailed Description

This is a phase 3, global, multi-center, randomized, double-blind, placebo-controlled study. This study is designed to determine the short- and long-term efficacy of reloxaliase in terms of reducing urinary oxalate excretion and clinical benefits compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Medizinische Universitat Wien, Innere Medizin III
• Belgium
  • Brussels, Belgium, 1020
    • UVC Brugmann University Hospital- Centre Hospitalier Universitaire
  • Bruxelles, Belgium, 1070
    • Universite Libre de Bruxelles -Hospital Erasme
  • Gent, Belgium, 90000
    • University Hospital Gent
• Brazil
  • Belo Horizonte, Brazil, MG-30130-100
    • Hospital das Clinicas da Ufmg
  • Santo André, Brazil, Sp-09060-870
    • Faculdade de Medicina do ABC
  • Santo André, Brazil, SP-09080-110
    • Pesquisare Saude
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas de Porto Alegre
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G1Z1
      • University of Alberta- Division of Urology
  • British Columbia
    • Victoria, British Columbia, Canada, V8T2C1
      • Silverado Research Inc
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
    • Québec, Quebec, Canada, G2J 0C4
      • ALPHA Recherche Clinique
• Croatia
  • Zagreb, Croatia, 10000
    • Polyclinic Solme
• France
  • Clichy, France, 92110
    • Hopital Beaujon_AP_HP
  • Marseille, France, 13385
    • AP-HM Hospital de la Conception
  • Paris, France, 75970
    • Hospital Tenon-AP-HP
  • Vandœuvre-lès-Nancy, France, 54500
    • CHRU de Nancy-Hopitaux de Brabois
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin- Berlin
  • München, Germany, 81377
    • Klinikum der Universitaet- Muenche
• Italy
  • Firenze, Italy, 50122
    • Azienda USL Toscana Centro-Ospedale Santa Maria Nuova
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Universitaria San Martino IST
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario A.Gemelli IRCCS - Universita Cattolica del Sacro Cuore
• Mexico
  • Chihuahua, Mexico, 31000
    • ICARO Investigaciones en Medicina SA de CV/Hospital Christus Muguerza
  • Ciudad de mexico, Mexico, 11650
    • Centro specializado en Diabetes, Obesidad y Prevencion de Enfermedades Cardiovasculares
  • Cuauhtémoc, Mexico, 06700
    • Clinstile, S.A. de C.V- Col. Roma Norte Delegacion
  • Gto, C.P
    • Irapuato, Gto, C.P, Mexico, 36650
      • Invesclinic MX
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Fernando da Fonseca
  • Porto, Portugal, 4200-319
    • Centro Hospitalar Universitario de Sao Joao
• Romania
  • Bucharest, Romania, 011025
    • SANA Medical Center
  • Bucharest, Romania, 50098
    • Spitalul Clinic Universitar de Urgenta Bucuresti
  • Bucuresti, Romania, 022328
    • Institutul Clinic Fundeni
  • Caracal, Romania, 235200
    • ClinTrial/County Hospital Caracal
  • Constanţa, Romania, 900590
    • Centru de Diagnostic si Tratament Affidea- Medicina Interna
• Russian Federation
  • Penza, Russian Federation, 440026
    • Clinic of Urology LLC
  • Saint Petersburg, Russian Federation, 191025
    • LLC Medsi St Petersburg
  • Saint Petersburg, Russian Federation, 194044
    • S.M Kirov Military Medical Academy
  • Saint Petersburg, Russian Federation, 194354
    • Medical Center "Reavita Med StP" LLC
  • Saint Petersburg, Russian Federation, 198205
    • City Hospital #15
  • Saratov, Russian Federation, 410054
    • Saratov State Medical University, n.a. V.I. Razumosky
• Spain
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Girona, Spain, 17007
    • Hospital Universitari de Girona
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitaetsspital Bern Inselspital Bern University Hospital
  • Lausanne, Switzerland, CH 1011
    • Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Nephrology Department
• United Kingdom
  • Cardiff, United Kingdom, CF144XW
    • University Hospital of Wales
  • Dartford, United Kingdom, DA2-8DA
    • Darent Valley Hospital
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital
  • South Shields, United Kingdom, NE34 0PL
    • South Tyneside District Hospital - South Shields
  • Wrexham, United Kingdom, LL13 7TD
    • Wrexham Maelor Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35234
      • University of Alabama- Department of Urology
    • Mobile, Alabama, United States, 36608
      • Alliance for Multispecialty Research, LLC
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Aventiv Research Inc.
    • Peoria, Arizona, United States, 85381
      • Arizona Kidney Disease and Hypertension Center (AKDHC)- Phoenix
    • Phoenix, Arizona, United States, 85016
      • Arizona Kidney Disease and Hypertension Center (AKDHC)- Glendale
    • Phoenix, Arizona, United States, 85054
      • Mayo Mercy Hospital
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Center
    • Tucson, Arizona, United States, 85715
      • Urological Associates of Southern Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urology
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center of Arkansas
  • California
    • Granada Hills, California, United States, 91344
      • Renal Consultants Medical Group
    • Northridge, California, United States, 91324
      • Amicis Research
    • San Diego, California, United States, 92103
      • University of California, San Diego (UCSD) Health System
    • San Francisco, California, United States, 94143
      • University of California- San Francisco (UCSF)
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
    • Vacaville, California, United States, 95688
      • Sutter Health- Sacramento
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • Florida
    • Coral Springs, Florida, United States, 33071
      • South Florida Nephrology Group PA Research Div
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Hialeah, Florida, United States, 33012
      • Quantum Clinical Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Miami Gardens, Florida, United States, 33014
      • Pro-Care Research Center, Corp
    • Pensacola, Florida, United States, 32503
      • Avanza Medical Research Center
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Idaho Catalyst Clinical Research
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute
  • Indiana
    • Carmel, Indiana, United States, 46032
      • IU Health Physicians
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (IU) Nephrology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Chesapeake Urology Associates, LLC d/b/a/ Chesapeake Urology Research Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48084
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic- Department of Nephrology Hyperoxaluria Center
  • Missouri
    • Columbia, Missouri, United States, 65211
      • University of Missouri Healthcare
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research, Inc
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Sheldon J. Freedman, MD
  • New York
    • Flushing, New York, United States, 11355
      • New York Presbyterian/Queens
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group
    • New York, New York, United States, 10016
      • New York University School of Medicine- Langone Medical Center
    • Rochester, New York, United States, 14620
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina (UNC) - Chapel Hill
    • Durham, North Carolina, United States, 27516
      • Duke University Medical Center
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologists of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati (UC) - Department of Nephrologyv
    • Columbus, Ohio, United States, 43210
      • Ohio State University (OSU)-Renal Division
    • Middleburg Heights, Ohio, United States, 44130
      • Clinical Research Solutions- Middleburg Heights
    • Toledo, Ohio, United States, 43606
      • Genito-Urinary Surgeons
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University (OHSU)
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02916
      • Lifespan Physician Group Minimally Invasive Urology Institute
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78745
      • Accelemed Research Institute
    • Dallas, Texas, United States, 75246
      • Renal Disease Research Institute
    • Houston, Texas, United States, 77027
      • Houston Metro Urology
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Research Institute- Temple
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin - Division of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provided informed consent
2. Age 18 years or older
3. Has an underlying enteric disorder associated with malabsorption with known or suspected history of hyperoxaluria (e.g., history of kidney stones or oxalate nephropathy)
4. Urinary oxalate ≥ 50 mg/24 hr
5. Has at least 1 documented kidney stone within 2 years

Exclusion Criteria:

1. Acute renal failure or estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2
2. Has a known genetic, congenital, or other cause of kidney stones
3. Unable or unwilling to discontinue Vitamin C supplementation >200mg daily
4. Cannot establish baseline kidney stone burden

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; placebo capsule	Drug: Placebo; Placebo 2 capsules, orally, with each meal/snack, 3 to 5 times per day; Other Names: Placebo capsule
Experimental: Reloxaliase; Reloxaliase (ALLN-177) 142 mg of oxalate decarboxylase (equivalent to 3,750 units of enzyme activity) per capsule	Drug: Reloxaliase; Reloxaliase 2 capsules, orally, with each meal/snack, 3 to 5 times per day; Other Names: Oxalate decarboxylase; ALLN-177

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in 24-hour urinary oxalate excretion during Weeks 1 to 4	Efficacy will be assessed based on percent change from baseline to the average across Weeks 1 to 4, derived from all 24-hour collections during Weeks 1 to 4 on treatment	4 weeks
Proportion of subjects with kidney stone disease progression (composite of symptomatic kidney stone(s) or finding of new or enlarged kidney stone(s) on imaging)	Efficacy will be assessed by comparing kidney stone disease progression event rate on reloxaliase vs. placebo	up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in 24-hour urinary oxalate excretion during Weeks 16-24	Efficacy will be assessed based on percent change from baseline to the average across Weeks 16-24, derived from all 24-hour collections during Weeks 16-24 on treatment	24 weeks
Proportion of subjects with a ≥ 20% reduction from baseline in 24-hour urinary oxalate excretion during Weeks 1-4	Efficacy will be assessed based on proportion of subjects with ≥ 20% reduction from baseline to the average across Weeks 1-4, derived from all 24-hour collections during Weeks 1-4 on treatment	4 weeks
Hospitalizations or emergency room (ER) visits or procedures for the management of kidney stones	Efficacy will be assessed by comparing utilization on reloxaliase vs. placebo	up to 48 months
Change in estimated glomerular filtration rate (eGFR) from baseline	Efficacy will be assessed by comparing the rate of change in eGFR on reloxaliase vs. placebo	up to 48 months

Collaborators and Investigators

• Sponsor: Allena Pharmaceuticals
• Investigators: Study Director: David Clark, MD, Allena Pharmaceuticals Inc

Publications and helpful links

General Publications

• Langman CB, Grujic D, Pease RM, Easter L, Nezzer J, Margolin A, Brettman L. 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.
• 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.

Helpful Links

• A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme
• ALLN-177, oral enzyme therapy for hyperoxaluria

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: February 18, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: hyperoxaluria; kidney stone; oxalate; enteric hyperoxaluria; kidney calcification
• Other Study ID Numbers: ALLN-177-302; 2018-000921-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No