Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy

Primary IgA Nephropathy Clinical Trial

— Nefigard  

Official title:

A Randomized, Double-blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy at Risk of Progressing to End-stage Renal Disease (NefIgArd)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03643965
• Other study ID #: Nef-301
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2018
• Est. completion date: July 10, 2023

Study information

• Verified date: July 2023
• Source: Calliditas Therapeutics AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall aim of the study is to evaluate the efficacy, safety, and tolerability of Nefecon 16 mg per day in the treatment of patients with primary IgAN (Immunoglobulin A nephropathy) at risk of progressing to end-stage renal disease (ESRD), despite maximum tolerated treatment with renin-angiotensin system (RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).

Description:

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety, and tolerability of oral Nefecon compared to matching placebo in patients with primary IgAN on a background of optimized RAS inhibitor therapy. The study will consist of 2 parts, Part A and Part B. Part A will include a 9 month blinded Treatment Period, and a 3-month Follow up Period. Part B of the study will consist of a 12-month observational Follow up Period; no study drug will be administered during Part B. Part A and B will be blinded. Safety will be monitored by an independent Data Safety Monitoring Board.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: July 10, 2023
• Est. primary completion date: July 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female or male patients =18 years

2. Biopsy-verified IgA nephropathy

3. Stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or Maximum Tolerated Dose (MTD) according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines

4. Urine protein creatinine ratio =1 g/24hr

5. eGFR =35 mL/min per 1.73 m2 and =90 mL/min per 1.73 m2 using the Chronic Kidney Diseae Epidemiology Collaboration (CKD-EPI) formula

6. Willing and able to give informed consent

Exclusion Criteria:

1. Systemic diseases that may cause mesangial IgA deposition.

2. Patients who have undergone a kidney transplant.

3. Patients with acute or chronic infectious disease including hepatitis, tuberculosis, human immunodeficiency virus (HIV), and chronic urinary tract infections.

4. Patients with liver cirrhosis, as assessed by the Investigator.

5. Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled.

6. Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator;

7. Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator

8. Patients with diagnosed malignancy within the past 5 years.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy

Intervention

Drug:
• Nefecon
Nefecon 16 mg for daily administration by mouth for 9 months.
• Placebo oral capsule
Placebo capsules for daily administration by mouth for 9 months.

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires, Pedriel 74	Capital federal
Argentina	Clinica Priv Velez Sarsfield	Córdoba
Argentina	Hospital Privado-Centro Medico de Cordoba, Naciones Unidas 346, Nefrologia piso 1	Córdoba
Argentina	Sanatorio Allende, Hipolito Yrigoyen 384, 2 Piso	Córdoba
Argentina	Hospital Universitario Austral, Unidad de Investigacion Clinica, Av. J.D. Peron 1500, piso 4	Pilar
Argentina	Clinico de Nefrologia, Urologia Y Enfermedades Cardiovasculares, Av. Gdor Freyre 3074	Santa Fe
Australia	Royal Adelaide Hospital, Port Rd.	Adelaide
Australia	Box Hill Hospital, Dept of Renal Medicine, Arnold Str 5	Box Hill
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Austin Health, Dept of Nephrology, 145 Studley Rd.	Heidelberg
Australia	Melbourne Health, Royal Melbourne Hospital, Dept of Nephrology,Grattan Str.	Parkville
Australia	Prince of Wales Hospital, Nephrology Dept, Parkes 3 West	Randwick
Australia	Western Health, Western Hospital-Sunshine Hospital, 176 Furlong Rd, Level 3, WHCRE Building	St Albans
Australia	Westmead Hospital, Dept of Renal Medicine, Hawkesbury Rd.	Westmead
Australia	Metro South Hospital and Health Service via Princess Alexandra Hospital, Dept of Nephrology, 199 Ipswich Rd.	Woolloongabba
Belarus	Brest Regional Hospital, 7 Meditsinskaya str.	Brest
Belarus	Gomel Regional Clinical Hospital, 5 Brat'ev Lizukovyh str.	Gomel
Belarus	Grodno Regional Clinical Hospital, 52 Bulvar Leninskogo Komsomola	Grodno
Belarus	4-th N.E. Savchenko City Clinical Hospital, 110, R. Luxemburg str.	Minsk
Belgium	Cliniques Universitaires Saint-Luc, Nephrology Dept, Av. Hippocrate 10	Brussel
Belgium	University Hospital Erasmus (Brussels), Recherche Clinique Nephrologie Transplantation, Route de Lennik 808	Brussels
Belgium	University Hospital Gent, Dept of Medical Nephrology, Corneel Heymanslaan 10	Gent
Belgium	Centre Hospitalier Universitaire de Liege, Nephrology Dept. Domaine Universitaire de Sart-Tilman	Liège
Belgium	AZ Delta, Wilgenstraat 2	Roeselare
Canada	CISSS de la Monteregie-Centre-Hopital Charles LeMoyne, Room E-304, 3120 Taschereau Blvd	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Sciences Centre, 1276 South Park St	Halifax	Nova Scotia
Canada	Royal Inland Hospital, Kidney Clinic, 7 South, 311 Columbia Street	Kamloops	British Columbia
Canada	Interior Health-Kelowna General Hosp (IH KGH), 2268 Pandosy Str.	Kelowna	British Columbia
Canada	Kingston General Hospital	Kingston	Ontario
Canada	CHUQ-L'Hotel Dieu de Quebec, 11 côte du Palais	Québec City	Quebec
Canada	Centre Hospiitalier Universitaire de Sherbrooke (CHUS), 3001, 12e Avenue Nord	Sherbrooke	Quebec
Canada	Hospital Maisonneuve-Rosemont, CNIB 3rd Floor, 1929 Bayview Avenue	Toronto	Ontario
Canada	Toronto General Hospital, University Health Network, 200 Elizabeth St, 8 N-849	Toronto	Ontario
Canada	Vancouver Coastal Health Authority, Gordon and Leslie Diamond Health Care Centre, 5 th floor, Diamond Building	Vancouver	British Columbia
Czechia	Fakultni nemocnice Brno, Interni gastroenterologicka klinika, Jihlavska 20	Brno
Czechia	Fakultni nemocnice Hradec Kralove, Sokolska 581	Hradec Králové
Czechia	Fakultni nemocnice Olomouc, I.P. Pavlova 185/6	Olomouc
Czechia	Fakultni nemocnice Kralovske Vinohrady, Linterni klinika, Srobarova 1150/50	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze, Klinik nefrologie, U Nemocnice 499/2	Praha 2
Finland	Helsinki University Central Hospital (HUCH), Nephrology Clinic, Meilahti Triangle Hospital	Helsinki
Finland	Study Cor Oy, Hoitajantie 4	Jyväskylä
Finland	Tampere University Hospital, P O Box 2000, Munuaiskeskus, Erakennus, 1. kerros	Tampere
France	Centre Hospitalier Boulogne sur Mer, 4eme etage Batiment Administratif, Allee Jacques Monod	Boulogne-sur-Mer
France	CHU Grenoble-Hopital Michallon, Service Nephrologie-Hemodialyse-Aphereses-Transplantation Renale, Boulevard de la Chantourne CS 10217	Grenoble
France	Lapeyronie Hospital, Univ Hospital Montpellier, 371 Av. du Doyen Gaston Giraud	Montpellier
France	Hopital Bichat-Claude Bernard, Service de Nephrologie, 46 rue Henri Huchard	Paris
France	Chu St Etienne-Hopital Nord, Service de Nephrologie Dialyse Transplantation renale, Av. Albert Raimond	Saint-Priest-en-Jarez
France	Centre Hospitalier de Valenciennes, Service de Nephrologie-Medecine Interne, Av. Desandrouin BP 379	Valenciennes
Germany	Uniklinik RWTH Aachen, Medizinische Klinik II, Pauwelsstrasse 30	Aachen
Germany	Universitaetsklinikum Carl Gustav Carus Dresden, Medizinische Klinik III, Nephrologie, Fetscherstr. 74	Dresden
Germany	Universitaetsklinikum Erlangen, Medizinisches Klinik 4, Ulmenweg 18	Erlangen
Germany	Universitaetsklinikum Heidelberg-Nephrologie, Renal Clinic, Im Neuenheimer Feld 162	Heidelberg
Germany	Universitatsklinik Schleswig-Holstein-Campus Lubek, Medizinische Klinik I, Nephrologie, Ratzeburger Allee 160	Lubeck
Germany	University Clinic Munich, LMU-Inner City Medical Polyclinic, Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV	Munich
Germany	Universitaetsklinikum Regensburg, Abteilung für Nephrologie, Franz-Josef-Strauss Allee 11	Regensburg
Greece	General Hospital of Athens-Laiko, Nephrology Clinic, 17 Agiou Thoma Street	Athens
Greece	University Hospital of Heraklion, Nephrology Clinic, Diastaurosi Staurakion-Vouton	Heraklion
Greece	University General Hospital of Ioannina, Nephrology Clinic, Leof. Stavros Niarchou	Ioánnina
Greece	University Hospital of Larissa Medical School, Nefrology Clinic, Mezourlo	Larissa
Greece	General Hospital of Nikaia Ag. Panteleimon, Nephrology Clinic, Mantouvalou 3 Str.	Níkaia
Greece	University General Hospital of Patras, Rio	Patras
Greece	Hippokration General Hosp of Thessaloniki, Nephrology Clinic, 49 Konstantinoupoleos Str	Thessaloníki
Italy	Azienda Ospedale Policlinico di Bari	Bari
Italy	ASST di Lecco, Presidio Ospedaliero Alessandro Manzoni, Via dell´Eremo 9/11	Lecco
Italy	Ospedale San Carlo Borromeo, Via Pio II, 3	Milano
Italy	Istituti Clinici Scientifici Maugeri Spa-Societa Benefit, Div. di Nephrologia ed Emodialist, Via S. Maugeri 10	Pavia
Korea, Republic of	Dong-A University Hospital, Won Suk An, 26 Daesingongwon-Ro Seogu	Busan
Korea, Republic of	Kyungpook National University Hospital, 130 Dongdeok-ro Jung-gu	Daegu
Korea, Republic of	Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu	Daejeon
Korea, Republic of	Hallym University Sacred Heart Hospital,22 Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si	Gyeonggi-do
Korea, Republic of	Chung-Ang University Hospial, 102 Heukseok-ro, Dongiak-gu	Seoul
Korea, Republic of	Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu	Seoul
Korea, Republic of	Seoul St. Mary´s Hospital, 222 Banpo-Daero, Seocho-gu	Seoul
Poland	Uniwersyteckie Centrum Kliniczne-Szpital Gdanskiego Uniwersytetu Medycznego	Gdansk
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny, Uniwersytetu Medycznego w Lodzi, ul Pomorska 251	Lódz
Poland	Wojewodzki Szpital Specjalistyczny w Olsztynie, Oddzial Kliniczny Nefrologiczny, Hipertensjologii i Chorob Wewnetrznych, ul. Zolnierska 18	Olsztyn
Poland	Sonomed Sp. z.o.o. ul. Bandurskiego 98/U12	Szczecin
Spain	Hospital Universitario Fundacion Alcorcon, C/Budapest 1	Alcorcón
Spain	Hospital Clinic Barcelona, Escalera 12, Planta 5, Calle Villaroel 170	Barcelona
Spain	Hospital del Mar, Passeig Maritim 25-29	Barcelona
Spain	Hospital Universitario Vall d´Hebron, Passeig Vall d´Hebron 119-129	Barcelona
Spain	Hospital Universitari Arnau de Vilanova, Avenida Alcalde Rovire Roure 80	Lleida
Spain	Hospital 12 de Octubre, Residencia General (Sotano 1)-Area de Ensayos Clinicos, Avda. Cordoba s/n	Madrid
Spain	Hospital General Universitario Gregorio Maranon, Servicio de Nefrologica, C/Dr. Esquerdo 46	Madrid
Sweden	Sahlgrenska University Hospital, Njurmottagningen, Vita Stråket 12	Göteborg
Sweden	Universitetssjukhuset Linköping, Njurmedicinska kliniken	Linköping
Sweden	Danderyds sjukhus, Njurmedicinska kliniken	Stockholm
Sweden	Karolinska University Hospital-Huddinge, Njur-KBC M87	Stockholm
Sweden	Uppsala University Hospital, Dept of Nephrology, ing 30, plan 5	Uppsala
Taiwan	Kaohsiung Medical Univ Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital, No 2 Yude Rd	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital, No 138 Sheng Li Rd	Tainan
Turkey	Cukurova University Medical Faculty, Dept of Internal Disease, Div of Nephrology, Balcali	Adana
Turkey	Istanbul University Cerrahpasa, Medical Faculty-Dept of Internal Disease, Fatih-Cerrahpasa, Kocamustafapasa Caddesi No 53	Istanbul
Turkey	Ege University Med Faculty Dept of Internal Disease, Div of Nephrology	Izmir
Turkey	Erciyes University Faculty of Medicine,Semiha Kibar Organ Nakli ve Dyaliz Hastanesi, Kosk Mah. prof dr Turhan Feyziogly Cad. no 42	Kayseri
Turkey	Kocaeli University Medical School-Internal Medicine, Nephrology, Umuttepe Yerleskesi	Kocaeli
United Kingdom	Belfast City Hospital, 51 Lisburn Rd	Belfast
United Kingdom	Southmead Hospital, Southmead Rd, Westbury-on-Trym	Bristol
United Kingdom	Queen Elizabeth University Hosp-Glasgow, Glasgow Clin Research Facility 5th floor, Institute of Neurosciences	Glasgow
United Kingdom	Gloucestershire Royal Hospital, Great Western Rd	Gloucester
United Kingdom	St James´s University Hospital, Beckett St.	Leeds
United Kingdom	Leicester General Hospital, John Walls Renal Unit, Gwendolen Rd	Leicester
United Kingdom	The Royal London Hospital, Whitechapel	London
United Kingdom	University of Manchester, Manchester Royal Infirmary, Oxford Rd	Manchester
United Kingdom	Nottingham City Hospital, Hucknall Rd	Nottingham
United Kingdom	Northern General Hospital, Herries Rd.	Sheffield
United States	Mountain Kidney & Hypertension Assoc, 10 McDowell St	Asheville	North Carolina
United States	University of Colorado Health Science Center, 1200 East 19th Av.	Aurora	Colorado
United States	University of Alabama at Birmingham, 1720 2nd Ave South	Birmingham	Alabama
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina at Chapel Hill, Clinical & Translational Research Centre	Chapel Hill	North Carolina
United States	Northwestern University the Feinberg School of Medicine, 633 North St. Clair	Chicago	Illinois
United States	Cleveland Clinic, Glickman Urological & Kidney Institute, 9500 Euclid Av.	Cleveland	Ohio
United States	The Ohio State University (OSU), Wexner Medical Center, 410 West 10th Av.	Columbus	Ohio
United States	Northshore University Health System, 2650 Ridge Av.	Evanston	Illinois
United States	Renal Disease Research Institute, 1250 Eighth Av. #135	Fort Worth	Texas
United States	University of Florida-Gainesville	Gainesville	Florida
United States	Queens Hospital Centre	Jamaica	New York
United States	Clinical Research Consultants, LLC, 3930 Washington St	Kansas City	Missouri
United States	University of Kentucky Medical Center, 800 Rose St, Pavillion H 3rd floor	Lexington	Kentucky
United States	University of Louisville-Nephrology	Louisville	Kentucky
United States	University of Minnesota, 717 Delaware St. SE	Minneapolis	Minnesota
United States	Nephrology Associates, P.C., 28 White Bridge Rd	Nashville	Tennessee
United States	Yale University School of Medicine, 330 Cedar Street	New Haven	Connecticut
United States	Columbia Univ Medical Center, Div of Nephrology, 51 Audubon Av	New York	New York
United States	Icahn School of Medicine at Mount Sinai-James J. Peters VA Medical Center, One Gustave L. Levy Place	New York	New York
United States	Omega Research Maitland	Orlando	Florida
United States	Omega Research Maitland, 7912 Forest City Rd.	Orlando	Florida
United States	Stanford University Medical Center, 777 Welch Rd	Palo Alto	California
United States	Thomas Jefferson University, 211 S. 9th Street	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital, 4800 Friendship Av.	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University, 3181 SW Sam Jackson Park Rd	Portland	Oregon
United States	Kidney Care and Transplant Services of New England, PC, 354 Birnie Av.	Springfield	Massachusetts
United States	Los Angeles Biomedical Research Institute at HUMC, 1124 W. Carson Street	Torrance	California
United States	Univ of Arizona, 1501 N Campbell Ave	Tucson	Arizona
United States	Washington Nephrology Associates-Washington DC, 730 24th Street NW	Washington	District of Columbia
United States	Western Nephrology and Metabolic Bone Disease, PC-Westerminster, 8410 Decatur St.	Westminster	Colorado
United States	Southeastern Nephrology-Whiteville, 800 Jefferson St	Whiteville	North Carolina
United States	Southeastern Nephrology Associates-Wilmington, 1302 Medical Center Drive	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Calliditas Therapeutics AB

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belarus,  Belgium,  Canada,  Czechia,  Finland,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Poland,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (1)

Fellstrom BC, Barratt J, Cook H, Coppo R, Feehally J, de Fijter JW, Floege J, Hetzel G, Jardine AG, Locatelli F, Maes BD, Mercer A, Ortiz F, Praga M, Sorensen SS, Tesar V, Del Vecchio L; NEFIGAN Trial Investigators. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017 May 27;389(10084):2117-2127. doi: 10.1016/S0140-6736(17)30550-0. Epub 2017 Mar 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Proteinuria, measured as Urine Protein to creatinine ratio (UPCR).	The primary outcome measure is UPCR (based on 24-hour urine collections) at 9 months following the first dose of study drug compared to baseline	9 months
Primary	Renal function measured as estimated glomerular filtration rate (eGFR)	Based on eGFR measure compared to baseline calculated using the CKD-EPI formula	Up to 2 years
Secondary	The incidence of treatment-emergent adverse events.	Adverse event data collection	From enrollment and up to 2 years
Secondary	Renal function	Renal function measured as eGFR using the CKD-EPI formula	Up to 2 years