Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria

NCT03847090 | Terminated Phase 3 DMC FDA Drug

• 2 other identifiers: ALLN-177-3022018-000921-29
• Study Type: interventional
• Target: 92
• Locations: 16 countries
• Sites: 113

Brief Summary

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

Conditions

Enteric Hyperoxaluria

Keywords

kidney stone; hyperoxaluria; enteric hyperoxaluria; oxalate; kidney calcification

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Percent change from baseline in 24-hour urinary oxalate excretion during Weeks 16-24

  24 weeks

• Proportion of subjects with a ≥ 20% reduction from baseline in 24-hour urinary oxalate excretion during Weeks 1-4

  4 weeks

• Hospitalizations or emergency room (ER) visits or procedures for the management of kidney stones

  up to 48 months

• Change in estimated glomerular filtration rate (eGFR) from baseline

  up to 48 months

Study Arms (2)

Reloxaliase

EXPERIMENTAL

Reloxaliase (ALLN-177) 142 mg of oxalate decarboxylase (equivalent to 3,750 units of enzyme activity) per capsule

Drug: Reloxaliase

placebo

PLACEBO COMPARATOR

placebo capsule

Drug: Placebo

Interventions

Reloxaliase DRUG

Reloxaliase 2 capsules, orally, with each meal/snack, 3 to 5 times per day

Also known as: ALLN-177, Oxalate decarboxylase

Reloxaliase

Placebo DRUG

Placebo 2 capsules, orally, with each meal/snack, 3 to 5 times per day

Also known as: Placebo capsule

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Allena Pharmaceuticals: lead

Study Sites (113)

University of Alabama- Department of Urology

Birmingham, Alabama, 35234, United States

Location

Alliance for Multispecialty Research, LLC

Mobile, Alabama, 36608, United States

Location

Aventiv Research Inc.

Mesa, Arizona, 85210, United States

Location

Arizona Kidney Disease and Hypertension Center (AKDHC)- Phoenix

Peoria, Arizona, 85381, United States

Location

Arizona Kidney Disease and Hypertension Center (AKDHC)- Glendale

Phoenix, Arizona, 85016, United States

Location

Mayo Mercy Hospital

Phoenix, Arizona, 85054, United States

Location

Urological Associates of Southern Arizona

Tucson, Arizona, 85715, United States

Location

Banner University Medical Center

Tucson, Arizona, 85724, United States

Location

Arkansas Urology

Little Rock, Arkansas, 72211, United States

Location

Applied Research Center of Arkansas

Little Rock, Arkansas, 72212, United States

Location

Renal Consultants Medical Group

Granada Hills, California, 91344, United States

Location

Amicis Research

Northridge, California, 91324, United States

Location

University of California, San Diego (UCSD) Health System

San Diego, California, 92103, United States

Location

University of California- San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Sutter Health- Sacramento

Vacaville, California, 95688, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

South Florida Nephrology Group PA Research Div

Coral Springs, Florida, 33071, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Quantum Clinical Research

Hialeah, Florida, 33012, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Pro-Care Research Center, Corp

Miami Gardens, Florida, 33014, United States

Location

Avanza Medical Research Center

Pensacola, Florida, 32503, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Idaho Catalyst Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Idaho Urologic Institute

Meridian, Idaho, 83642, United States

Location

IU Health Physicians

Carmel, Indiana, 46032, United States

Location

Indiana University (IU) Nephrology

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Regional Urology

Shreveport, Louisiana, 71106, United States

Location

Chesapeake Urology Associates, LLC d/b/a/ Chesapeake Urology Research Associates

Glen Burnie, Maryland, 21061, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48084, United States

Location

Mayo Clinic- Department of Nephrology Hyperoxaluria Center

Rochester, Minnesota, 55905, United States

Location

University of Missouri Healthcare

Columbia, Missouri, 65211, United States

Location

Montana Medical Research, Inc

Missoula, Montana, 59808, United States

Location

Sheldon J. Freedman, MD

Las Vegas, Nevada, 89144, United States

Location

New York Presbyterian/Queens

Flushing, New York, 11355, United States

Location

Long Island Gastrointestinal Research Group

Great Neck, New York, 11023, United States

Location

New York University School of Medicine- Langone Medical Center

New York, New York, 10016, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

University of North Carolina (UNC) - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27516, United States

Location

Associated Urologists of North Carolina

Raleigh, North Carolina, 27612, United States

Location

University of Cincinnati (UC) - Department of Nephrologyv

Cincinnati, Ohio, 45267, United States

Location

Ohio State University (OSU)-Renal Division

Columbus, Ohio, 43210, United States

Location

Clinical Research Solutions- Middleburg Heights

Middleburg Heights, Ohio, 44130, United States

Location

Genito-Urinary Surgeons

Toledo, Ohio, 43606, United States

Location

Oregon Health and Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

Lifespan Physician Group Minimally Invasive Urology Institute

Providence, Rhode Island, 02916, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Accelemed Research Institute

Austin, Texas, 78745, United States

Location

Renal Disease Research Institute

Dallas, Texas, 75246, United States

Location

Houston Metro Urology

Houston, Texas, 77027, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Urology San Antonio Research

San Antonio, Texas, 78229, United States

Location

Baylor Scott and White Research Institute- Temple

Temple, Texas, 76508, United States

Location

Virginia Urology

Richmond, Virginia, 23235, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

University of Wisconsin - Division of Nephrology

Madison, Wisconsin, 53705, United States

Location

Medizinische Universitat Wien, Innere Medizin III

Vienna, 1090, Austria

Location

UVC Brugmann University Hospital- Centre Hospitalier Universitaire

Brussels, 1020, Belgium

Location

Universite Libre de Bruxelles -Hospital Erasme

Brussels, 1070, Belgium

Location

University Hospital Gent

Ghent, 90000, Belgium

Location

Hospital das Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital das Clinicas da UFMG

Belo Horizonte, MG-30130-100, Brazil

Location

Faculdade de Medicina do ABC

Santo André, Sp-09060-870, Brazil

Location

Pesquisare Saude

Santo André, SP-09080-110, Brazil

Location

University of Alberta- Division of Urology

Edmonton, Alberta, T6G1Z1, Canada

Location

Silverado Research Inc

Victoria, British Columbia, V8T2C1, Canada

Location

Centre de Recherche Du Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

Location

Alpha Recherche Clinique

Québec, Quebec, G2J 0C4, Canada

Location

Polyclinic Solme

Zagreb, 10000, Croatia

Location

Hopital Beaujon_AP_HP

Clichy, 92110, France

Location

AP-HM Hospital de la Conception

Marseille, 13385, France

Location

Hospital Tenon-AP-HP

Paris, 75970, France

Location

CHRU de Nancy-Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Charite Universitaetsmedizin- Berlin

Berlin, 10117, Germany

Location

Klinikum der Universitaet- Muenche

München, 81377, Germany

Location

Azienda USL Toscana Centro-Ospedale Santa Maria Nuova

Florence, 50122, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino IST

Genova, 16132, Italy

Location

Fondazione Policlinico Universitario A.Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

Invesclinic MX

Irapuato, Gto, C.P, 36650, Mexico

Location

ICARO Investigaciones en Medicina SA de CV/Hospital Christus Muguerza

Chihuahua City, 31000, Mexico

Location

Clinstile, S.A. de C.V- Col. Roma Norte Delegacion

Cuauhtémoc, 06700, Mexico

Location

Centro specializado en Diabetes, Obesidad y Prevencion de Enfermedades Cardiovasculares

Mexico City, 11650, Mexico

Location

Hospital Fernando da Fonseca

Amadora, 2720-276, Portugal

Location

Centro Hospitalar Universitario de Sao Joao

Porto, 4200-319, Portugal

Location

Sana Medical Center

Bucharest, 011025, Romania

Location

Institutul Clinic Fundeni

Bucharest, 022328, Romania

Location

Spitalul Clinic Universitar de Urgenta Bucuresti

Bucharest, 50098, Romania

Location

ClinTrial/County Hospital Caracal

Caracal, 235200, Romania

Location

Centru de Diagnostic si Tratament Affidea- Medicina Interna

Constanța, 900590, Romania

Location

Clinic of Urology LLC

Penza, 440026, Russia

Location

LLC Medsi St Petersburg

Saint Petersburg, 191025, Russia

Location

S.M Kirov Military Medical Academy

Saint Petersburg, 194044, Russia

Location

Medical Center "Reavita Med StP" LLC

Saint Petersburg, 194354, Russia

Location

City Hospital #15

Saint Petersburg, 198205, Russia

Location

Saratov State Medical University, n.a. V.I. Razumosky

Saratov, 410054, Russia

Location

Fundacio Puigvert

Barcelona, 08025, Spain

Location

Hospital Universitari de Girona

Girona, 17007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Inselspital, Universitaetsspital Bern Inselspital Bern University Hospital

Bern, 3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Nephrology Department

Lausanne, CH 1011, Switzerland

Location

University Hospital of Wales

Cardiff, CF144XW, United Kingdom

Location

Darent Valley Hospital

Dartford, DA2-8DA, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

South Tyneside District Hospital - South Shields

South Shields, NE34 0PL, United Kingdom

Location

Wrexham Maelor Hospital

Wrexham, LL13 7TD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27529510 BACKGROUND

• 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 BACKGROUND

Related 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

MeSH Terms

Conditions

Kidney Calculi; Hyperoxaluria

Interventions

reloxaliase; oxalate decarboxylase

Condition Hierarchy (Ancestors)

Nephrolithiasis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• David Clark, MD

  Allena Pharmaceuticals Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: February 20, 2019
• Study Start: August 26, 2019
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: June 10, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6); CH (2); DE (2); BE (3); ME (4); BR (4); CR (1); IT (3); US (64); PT (2); AU (1); RO (5); GB (5); ES (3); FR (4); CA (4)