Clinical trial NCT03643965: Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary IgA Nephropathy
Keywords: IgA Nephropathy
Lead sponsor: Calliditas Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2018-08-23
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Ratio of Urine Protein to Creatinine Ratio (UPCR) at 9 Months Compared to Baseline
timeFrame: 9 months
measure: Part B: Time-weighted Average of Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Up to 2 years and 1 month
Secondary outcomes:
measure: Part A: Ratio of eGFR at 9 Months
timeFrame: 9 months
measure: Part A: Ratio of eGFR at 12 Months
timeFrame: 12 months
measure: Part A: Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months
timeFrame: 9 months
measure: Part B: Time to 30% Reduction in eGFR
timeFrame: Over 2 years
measure: Part B: Time to Receiving Rescue Medication.
timeFrame: Over 2 years
measure: Part B: Ratio of UPCR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months
timeFrame: 12, 18 and 24 months
measure: Part B: Ratio of UACR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months
timeFrame: 12 to 24 months
measure: Part B: Ratio of eGFR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months
timeFrame: 12 to 24 months
measure: Part B: Proportion of Patients Without Microhematuria
timeFrame: 12 to 24 months
measure: Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months.
timeFrame: 9 months
measure: Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months.
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, 1720 2nd Ave South
state: Alabama
city: Tucson
country: United States
facility: Univ of Arizona, 1501 N Campbell Ave
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University Medical Center, 777 Welch Rd
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at HUMC, 1124 W. Carson Street
state: California
city: Aurora
country: United States
facility: University of Colorado Health Science Center, 1200 East 19th Av.
state: Colorado
city: Westminster
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC-Westerminster, 8410 Decatur St.
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine, 330 Cedar Street
state: Connecticut
city: Washington
country: United States
facility: Washington Nephrology Associates-Washington DC, 730 24th Street NW
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida-Gainesville
state: Florida
city: Orlando
country: United States
facility: Omega Research Maitland, 7912 Forest City Rd.
state: Florida
city: Orlando
country: United States
facility: Omega Research Maitland
state: Florida
city: Chicago
country: United States
facility: Northwestern University the Feinberg School of Medicine, 633 North St. Clair
state: Illinois
city: Evanston
country: United States
facility: Northshore University Health System, 2650 Ridge Av.
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Medical Center, 800 Rose St, Pavillion H 3rd floor
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville-Nephrology
state: Kentucky
city: Springfield
country: United States
facility: Kidney Care and Transplant Services of New England, PC, 354 Birnie Av.
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, 717 Delaware St. SE
state: Minnesota
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC, 3930 Washington St
state: Missouri
city: Jamaica
country: United States
facility: Queens Hospital Centre
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai-James J. Peters VA Medical Center, One Gustave L. Levy Place
state: New York
city: New York
country: United States
facility: Columbia Univ Medical Center, Div of Nephrology, 51 Audubon Av
state: New York
city: Asheville
country: United States
facility: Mountain Kidney & Hypertension Assoc, 10 McDowell St
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, Clinical & Translational Research Centre
state: North Carolina
city: Whiteville
country: United States
facility: Southeastern Nephrology-Whiteville, 800 Jefferson St
state: North Carolina
city: Wilmington
country: United States
facility: Southeastern Nephrology Associates-Wilmington, 1302 Medical Center Drive
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic, Glickman Urological & Kidney Institute, 9500 Euclid Av.
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University (OSU), Wexner Medical Center, 410 West 10th Av.
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University, 3181 SW Sam Jackson Park Rd
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, 211 S. 9th Street
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital, 4800 Friendship Av.
state: Pennsylvania
city: Nashville
country: United States
facility: Nephrology Associates, P.C., 28 White Bridge Rd
state: Tennessee
city: Fort Worth
country: United States
facility: Renal Disease Research Institute, 1250 Eighth Av. #135
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Capital federal
country: Argentina
facility: Hospital Britanico de Buenos Aires, Pedriel 74
city: Córdoba
country: Argentina
facility: Clinica Priv Velez Sarsfield
city: Córdoba
country: Argentina
facility: Hospital Privado-Centro Medico de Cordoba, Naciones Unidas 346, Nefrologia piso 1
city: Córdoba
country: Argentina
facility: Sanatorio Allende, Hipolito Yrigoyen 384, 2 Piso
city: Pilar
country: Argentina
facility: Hospital Universitario Austral, Unidad de Investigacion Clinica, Av. J.D. Peron 1500, piso 4
city: Santa Fe
country: Argentina
facility: Clinico de Nefrologia, Urologia Y Enfermedades Cardiovasculares, Av. Gdor Freyre 3074
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital, Port Rd.
city: Box Hill
country: Australia
facility: Box Hill Hospital, Dept of Renal Medicine, Arnold Str 5
city: Heidelberg
country: Australia
facility: Austin Health, Dept of Nephrology, 145 Studley Rd.
city: Parkville
country: Australia
facility: Melbourne Health, Royal Melbourne Hospital, Dept of Nephrology,Grattan Str.
city: Randwick
country: Australia
facility: Prince of Wales Hospital, Nephrology Dept, Parkes 3 West
city: St Albans
country: Australia
facility: Western Health, Western Hospital-Sunshine Hospital, 176 Furlong Rd, Level 3, WHCRE Building
city: Westmead
country: Australia
facility: Westmead Hospital, Dept of Renal Medicine, Hawkesbury Rd.
city: Woolloongabba
country: Australia
facility: Metro South Hospital and Health Service via Princess Alexandra Hospital, Dept of Nephrology, 199 Ipswich Rd.
city: Brest
country: Belarus
facility: Brest Regional Hospital, 7 Meditsinskaya str.
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital, 5 Brat'ev Lizukovyh str.
city: Grodno
country: Belarus
facility: Grodno Regional Clinical Hospital, 52 Bulvar Leninskogo Komsomola
city: Minsk
country: Belarus
facility: 4-th N.E. Savchenko City Clinical Hospital, 110, R. Luxemburg str.
city: Brussels
country: Belgium
facility: University Hospital Erasmus (Brussels), Recherche Clinique Nephrologie Transplantation, Route de Lennik 808
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc, Nephrology Dept, Av. Hippocrate 10
city: Gent
country: Belgium
facility: University Hospital Gent, Dept of Medical Nephrology, Corneel Heymanslaan 10
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liege, Nephrology Dept. Domaine Universitaire de Sart-Tilman
city: Roeselare
country: Belgium
facility: AZ Delta, Wilgenstraat 2
city: Kamloops
country: Canada
facility: Royal Inland Hospital, Kidney Clinic, 7 South, 311 Columbia Street
state: British Columbia
city: Kelowna
country: Canada
facility: Interior Health-Kelowna General Hosp (IH KGH), 2268 Pandosy Str.
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Authority, Gordon and Leslie Diamond Health Care Centre, 5 th floor, Diamond Building
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre, 1276 South Park St
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Hospital Maisonneuve-Rosemont, CNIB 3rd Floor, 1929 Bayview Avenue
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network, 200 Elizabeth St, 8 N-849
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre-Hopital Charles LeMoyne, Room E-304, 3120 Taschereau Blvd
state: Quebec
city: Québec City
country: Canada
facility: CHUQ-L'Hotel Dieu de Quebec, 11 côte du Palais
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospiitalier Universitaire de Sherbrooke (CHUS), 3001, 12e Avenue Nord
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Interni gastroenterologicka klinika, Jihlavska 20
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove, Sokolska 581
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc, I.P. Pavlova 185/6
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady, Linterni klinika, Srobarova 1150/50
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze, Klinik nefrologie, U Nemocnice 499/2
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital (HUCH), Nephrology Clinic, Meilahti Triangle Hospital
city: Jyväskylä
country: Finland
facility: Study Cor Oy, Hoitajantie 4
city: Tampere
country: Finland
facility: Tampere University Hospital, P O Box 2000, Munuaiskeskus, Erakennus, 1. kerros
city: Boulogne-sur-Mer
country: France
facility: Centre Hospitalier Boulogne sur Mer, 4eme etage Batiment Administratif, Allee Jacques Monod
city: Grenoble
country: France
facility: CHU Grenoble-Hopital Michallon, Service Nephrologie-Hemodialyse-Aphereses-Transplantation Renale, Boulevard de la Chantourne CS 10217
city: Montpellier
country: France
facility: Lapeyronie Hospital, Univ Hospital Montpellier, 371 Av. du Doyen Gaston Giraud
city: Paris
country: France
facility: Hopital Bichat-Claude Bernard, Service de Nephrologie, 46 rue Henri Huchard
city: Saint-Priest-en-Jarez
country: France
facility: Chu St Etienne-Hopital Nord, Service de Nephrologie Dialyse Transplantation renale, Av. Albert Raimond
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes, Service de Nephrologie-Medecine Interne, Av. Desandrouin BP 379
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen, Medizinische Klinik II, Pauwelsstrasse 30
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden, Medizinische Klinik III, Nephrologie, Fetscherstr. 74
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen, Medizinisches Klinik 4, Ulmenweg 18
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg-Nephrologie, Renal Clinic, Im Neuenheimer Feld 162
city: Lubeck
country: Germany
facility: Universitatsklinik Schleswig-Holstein-Campus Lubek, Medizinische Klinik I, Nephrologie, Ratzeburger Allee 160
city: Munich
country: Germany
facility: University Clinic Munich, LMU-Inner City Medical Polyclinic, Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg, Abteilung für Nephrologie, Franz-Josef-Strauss Allee 11
city: Athens
country: Greece
facility: General Hospital of Athens-Laiko, Nephrology Clinic, 17 Agiou Thoma Street
city: Heraklion
country: Greece
facility: University Hospital of Heraklion, Nephrology Clinic, Diastaurosi Staurakion-Vouton
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina, Nephrology Clinic, Leof. Stavros Niarchou
city: Larissa
country: Greece
facility: University Hospital of Larissa Medical School, Nefrology Clinic, Mezourlo
city: Níkaia
country: Greece
facility: General Hospital of Nikaia Ag. Panteleimon, Nephrology Clinic, Mantouvalou 3 Str.
city: Patras
country: Greece
facility: University General Hospital of Patras, Rio
city: Thessaloníki
country: Greece
facility: Hippokration General Hosp of Thessaloniki, Nephrology Clinic, 49 Konstantinoupoleos Str
city: Bari
country: Italy
facility: Azienda Ospedale Policlinico di Bari
city: Lecco
country: Italy
facility: ASST di Lecco, Presidio Ospedaliero Alessandro Manzoni, Via dell´Eremo 9/11
city: Milano
country: Italy
facility: Ospedale San Carlo Borromeo, Via Pio II, 3
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri Spa-Societa Benefit, Div. di Nephrologia ed Emodialist, Via S. Maugeri 10
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital, Won Suk An, 26 Daesingongwon-Ro Seogu
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital, 130 Dongdeok-ro Jung-gu
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu
city: Gyeonggi-do
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital,22 Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary´s Hospital, 222 Banpo-Daero, Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospial, 102 Heukseok-ro, Dongiak-gu
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Szpital Gdanskiego Uniwersytetu Medycznego
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Olsztynie, Oddzial Kliniczny Nefrologiczny, Hipertensjologii i Chorob Wewnetrznych, ul. Zolnierska 18
city: Szczecin
country: Poland
facility: Sonomed Sp. z.o.o. ul. Bandurskiego 98/U12
city: Łódź
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny, Uniwersytetu Medycznego w Lodzi, ul Pomorska 251
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundacion Alcorcon, C/Budapest 1
city: Barcelona
country: Spain
facility: Hospital del Mar, Passeig Maritim 25-29
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron, Passeig Vall d´Hebron 119-129
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona, Escalera 12, Planta 5, Calle Villaroel 170
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova, Avenida Alcalde Rovire Roure 80
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon, Servicio de Nefrologica, C/Dr. Esquerdo 46
city: Madrid
country: Spain
facility: Hospital 12 de Octubre, Residencia General (Sotano 1)-Area de Ensayos Clinicos, Avda. Cordoba s/n
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital, Njurmottagningen, Vita Stråket 12
city: Linköping
country: Sweden
facility: Universitetssjukhuset Linköping, Njurmedicinska kliniken
city: Stockholm
country: Sweden
facility: Karolinska University Hospital-Huddinge, Njur-KBC M87
city: Stockholm
country: Sweden
facility: Danderyds sjukhus, Njurmedicinska kliniken
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Dept of Nephrology, ing 30, plan 5
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical Univ Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital, No 2 Yude Rd
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital, No 138 Sheng Li Rd
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty, Dept of Internal Disease, Div of Nephrology, Balcali
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa, Medical Faculty-Dept of Internal Disease, Fatih-Cerrahpasa, Kocamustafapasa Caddesi No 53
city: İzmir
country: Turkey
facility: Ege University Med Faculty Dept of Internal Disease, Div of Nephrology
city: Kayseri
country: Turkey
facility: Erciyes University Faculty of Medicine,Semiha Kibar Organ Nakli ve Dyaliz Hastanesi, Kosk Mah. prof dr Turhan Feyziogly Cad. no 42
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical School-Internal Medicine, Nephrology, Umuttepe Yerleskesi
city: Belfast
country: United Kingdom
facility: Belfast City Hospital, 51 Lisburn Rd
city: Bristol
country: United Kingdom
facility: Southmead Hospital, Southmead Rd, Westbury-on-Trym
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hosp-Glasgow, Glasgow Clin Research Facility 5th floor, Institute of Neurosciences
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital, Great Western Rd
city: Leeds
country: United Kingdom
facility: St James´s University Hospital, Beckett St.
city: Leicester
country: United Kingdom
facility: Leicester General Hospital, John Walls Renal Unit, Gwendolen Rd
city: London
country: United Kingdom
facility: The Royal London Hospital, Whitechapel
city: Manchester
country: United Kingdom
facility: University of Manchester, Manchester Royal Infirmary, Oxford Rd
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital, Hucknall Rd
city: Sheffield
country: United Kingdom
facility: Northern General Hospital, Herries Rd.
Study officials:
affiliation: Calliditas AB
name: Krassimir Mitchev, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Barratt J, Lafayette R, Kristensen J, Stone A, Cattran D, Floege J, Tesar V, Trimarchi H, Zhang H, Eren N, Paliege A, Rovin BH; NefIgArd Trial Investigators. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int. 2023 Feb;103(2):391-402. doi: 10.1016/j.kint.2022.09.017. Epub 2022 Oct 19.