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

Enteric Hyperoxaluria Clinical Trial

— URIROX-2  

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03847090
• Other study ID #: ALLN-177-302
• Secondary ID: 2018-000921-29
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2019
• Est. completion date: May 19, 2022

Study information

• Verified date: June 2022
• Source: Allena Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: May 19, 2022
• Est. primary completion date: May 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Enteric Hyperoxaluria

Intervention

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

Locations

Country	Name	City	State
Austria	Medizinische Universitat Wien, Innere Medizin III	Wien
Belgium	UVC Brugmann University Hospital- Centre Hospitalier Universitaire	Brussels
Belgium	Universite Libre de Bruxelles -Hospital Erasme	Bruxelles
Belgium	University Hospital Gent	Gent
Brazil	Hospital das Clinicas da UFMG	Belo Horizonte
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre	RS
Brazil	Faculdade de Medicina do ABC	Santo André
Brazil	Pesquisare Saude	Santo André
Canada	University of Alberta- Division of Urology	Edmonton	Alberta
Canada	Centre de Recherche Du Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Alpha Recherche Clinique	Québec	Quebec
Canada	Silverado Research Inc	Victoria	British Columbia
Croatia	Polyclinic Solme	Zagreb
France	Hopital Beaujon_AP_HP	Clichy
France	AP-HM Hospital de la Conception	Marseille
France	Hospital Tenon-AP-HP	Paris
France	CHRU de Nancy-Hopitaux de Brabois	Vandœuvre-lès-Nancy
Germany	Charite Universitaetsmedizin- Berlin	Berlin
Germany	Klinikum der Universitaet- Muenche	München
Italy	Azienda USL Toscana Centro-Ospedale Santa Maria Nuova	Firenze
Italy	IRCCS Azienda Ospedaliera Universitaria San Martino IST	Genova
Italy	Fondazione Policlinico Universitario A.Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Rome
Mexico	ICARO Investigaciones en Medicina SA de CV/Hospital Christus Muguerza	Chihuahua
Mexico	Centro specializado en Diabetes, Obesidad y Prevencion de Enfermedades Cardiovasculares	Ciudad de mexico
Mexico	Clinstile, S.A. de C.V- Col. Roma Norte Delegacion	Cuauhtémoc
Mexico	Invesclinic MX	Irapuato	Gto, C.P
Portugal	Hospital Fernando da Fonseca	Amadora
Portugal	Centro Hospitalar Universitario de Sao Joao	Porto
Romania	Sana Medical Center	Bucharest
Romania	Spitalul Clinic Universitar de Urgenta Bucuresti	Bucharest
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	ClinTrial/County Hospital Caracal	Caracal
Romania	Centru de Diagnostic si Tratament Affidea- Medicina Interna	Constanta
Russian Federation	Clinic of Urology LLC	Penza
Russian Federation	City Hospital #15	Saint Petersburg
Russian Federation	LLC Medsi St Petersburg	Saint Petersburg
Russian Federation	Medical Center "Reavita Med StP" LLC	Saint Petersburg
Russian Federation	S.M Kirov Military Medical Academy	Saint Petersburg
Russian Federation	Saratov State Medical University, n.a. V.I. Razumosky	Saratov
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital Universitari de Girona	Girona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Switzerland	Inselspital, Universitaetsspital Bern Inselspital Bern University Hospital	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Nephrology Department	Lausanne
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Darent Valley Hospital	Dartford
United Kingdom	The Royal Free Hospital	London
United Kingdom	South Tyneside District Hospital - South Shields	South Shields
United Kingdom	Wrexham Maelor Hospital	Wrexham
United States	University of Michigan	Ann Arbor	Michigan
United States	Accelemed Research Institute	Austin	Texas
United States	Northeast Clinical Research Center	Bethlehem	Pennsylvania
United States	University of Alabama- Department of Urology	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	IU Health Physicians	Carmel	Indiana
United States	University of North Carolina (UNC) - Chapel Hill	Chapel Hill	North Carolina
United States	University of Cincinnati (UC) - Department of Nephrologyv	Cincinnati	Ohio
United States	University of Missouri Healthcare	Columbia	Missouri
United States	Ohio State University (OSU)-Renal Division	Columbus	Ohio
United States	South Florida Nephrology Group PA Research Div	Coral Springs	Florida
United States	Renal Disease Research Institute	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	New York Presbyterian/Queens	Flushing	New York
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Chesapeake Urology Associates, LLC d/b/a/ Chesapeake Urology Research Associates	Glen Burnie	Maryland
United States	Renal Consultants Medical Group	Granada Hills	California
United States	Long Island Gastrointestinal Research Group	Great Neck	New York
United States	Quantum Clinical Research	Hialeah	Florida
United States	Houston Metro Urology	Houston	Texas
United States	Idaho Catalyst Clinical Research	Idaho Falls	Idaho
United States	Indiana University (IU) Nephrology	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Sheldon J. Freedman, MD	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	Applied Research Center of Arkansas	Little Rock	Arkansas
United States	Arkansas Urology	Little Rock	Arkansas
United States	University of Wisconsin - Division of Nephrology	Madison	Wisconsin
United States	Idaho Urologic Institute	Meridian	Idaho
United States	Aventiv Research Inc.	Mesa	Arizona
United States	Pro-Care Research Center, Corp	Miami Gardens	Florida
United States	Clinical Research Solutions- Middleburg Heights	Middleburg Heights	Ohio
United States	Montana Medical Research, Inc	Missoula	Montana
United States	Alliance for Multispecialty Research, LLC	Mobile	Alabama
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	New York University School of Medicine- Langone Medical Center	New York	New York
United States	Amicis Research	Northridge	California
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Arizona Kidney Disease and Hypertension Center (AKDHC)- Phoenix	Peoria	Arizona
United States	Arizona Kidney Disease and Hypertension Center (AKDHC)- Glendale	Phoenix	Arizona
United States	Mayo Mercy Hospital	Phoenix	Arizona
United States	Oregon Health and Science University (OHSU)	Portland	Oregon
United States	Lifespan Physician Group Minimally Invasive Urology Institute	Providence	Rhode Island
United States	Associated Urologists of North Carolina	Raleigh	North Carolina
United States	Virginia Urology	Richmond	Virginia
United States	Mayo Clinic- Department of Nephrology Hyperoxaluria Center	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Urology San Antonio Research	San Antonio	Texas
United States	University of California, San Diego (UCSD) Health System	San Diego	California
United States	University of California- San Francisco (UCSF)	San Francisco	California
United States	Regional Urology	Shreveport	Louisiana
United States	Stanford University School of Medicine	Stanford	California
United States	University of South Florida	Tampa	Florida
United States	Baylor Scott and White Research Institute- Temple	Temple	Texas
United States	Genito-Urinary Surgeons	Toledo	Ohio
United States	Banner University Medical Center	Tucson	Arizona
United States	Urological Associates of Southern Arizona	Tucson	Arizona
United States	Sutter Health- Sacramento	Vacaville	California
United States	Urology of Virginia	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Allena Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  France,  Germany,  Italy,  Mexico,  Portugal,  Romania,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

References & 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External 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