Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
APPLAUSE-IgAN
A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase III Study to Evaluate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
1 other identifier
interventional
518
34 countries
175
Brief Summary
The study is designed as a multicenter, randomized, double-blind, placebo controlled study to demonstrate the superiority of iptacopan (LNP023) at a dose of 200 mg b.i.d. compared to placebo on top of maximally tolerated ACEi or ARB on reduction of proteinuria and slowing renal disease progression in primary IgA Nephropathy patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2021
Longer than P75 for phase_3
175 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 9, 2020
CompletedFirst Posted
Study publicly available on registry
October 8, 2020
CompletedStudy Start
First participant enrolled
January 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 19, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 19, 2025
CompletedDecember 23, 2025
December 1, 2025
4.7 years
September 9, 2020
December 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at 9 months
Evaluated at interim analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein to Creatinine Ratio sampled from a 24h urine collection.
Baseline and 9 months
Annualized total estimated Glomerular Filtration Rate (eGFR) slope over 24 months).
Evaluated at the final analysis - to demonstrate superiority of LNP023 vs. placebo in slowing IgAN progression measured by the annualized total slope of Estimated Glomerular Filtration Rate (eGFR) change over 24 months.
Baseline and 24 months
Secondary Outcomes (8)
Change from baseline in estimated glomerular filtration rate at 9 months
Baseline and 9 months
Proportion of participants reaching Urine Protein To Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant or other newly approved drugs or initiating new background therapy for treatment of IgAN or Kidney Replacement Therapy (KRT)
Baseline and 9 months
Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months
Baseline and 12 months
Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire
Baseline and 9 months
Time from randomization to first occurrence of composite kidney failure endpoint event
Up to 24 months
- +3 more secondary outcomes
Study Arms (2)
LNP023 200mg b.i.d
EXPERIMENTALPlacebo to LNP023 200mg b.i.d
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmed IgA nephropathy as follows:
- For patients eGFR\* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required.
- For patients with eGFR\* 30 to \<45ml/min/1.73m2, a qualifying biopsy performed within 2 years with \< 50% tubulointerstitial fibrosis is required.
- For patients with eGFR\* 20 to \<30ml/min/1.73m2, a qualifying biopsy performed at any time.
- In all cases, if a historical biopsy is not available, one may be performed during screening. \*eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)
- Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
- Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
- If not previously vaccinated, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration.
- All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for approximately 90 days before first study drug administration. In addition, if patients are taking diuretics, other antihypertensive medication, or other background medication for IgAN, the doses should also be stabilized for approximately 90 days prior to the first dosing of study treatment.
You may not qualify if:
- Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
- Sitting office SBP \>140 mmHg or DBP \>90 mmHg at the randomization visit
- Patients previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (\>7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration. Participants previously or currently treated with oral budesonide. Participants treated with endothelin (receptor) antagonists within 90 days prior to first study drug administration.
- Prior use of iptacopan (LNP023) or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo
- History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
- Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (177)
AZ Kidney Dise and Hypertension Ctr
Glendale, Arizona, 85306, United States
AKDHC Medical Research ServicesLLC
Phoenix, Arizona, 85016, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
Kaiser Permanente
San Diego, California, 92111, United States
North America Research Institute
San Dimas, California, 91773, United States
University of Colorado Anschutz
Aurora, Colorado, 80045, United States
Nephrology Associates PA
Newark, Delaware, 19713, United States
Boise Kidney and Hypertension
Boise, Idaho, 83706, United States
CaRe Research
Chubbuck, Idaho, 83202, United States
Nep Assoc of Northern Illinois
Hinsdale, Illinois, 60521, United States
Renal Associates of Baton Rouge
Baton Rouge, Louisiana, 80808, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Brigham and Womens Hosp Harvard Med School
Boston, Massachusetts, 02115, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Clin Rsrch Consult a JCCT Company
Kansas City, Missouri, 64111, United States
DaVita Clinical Research
Las Vegas, Nevada, 89146, United States
New Jersey Kidney Care
Jersey City, New Jersey, 07305, United States
Columbia University Irving Medical
New York, New York, 10032, United States
Dallas Renal Group
Dallas, Texas, 75230, United States
Prolato Clinical Research Center
Houston, Texas, 77054, United States
Univ of Washington Medi Cen
Seattle, Washington, 98104, United States
Novartis Investigative Site
Córdoba, Córdoba Province, X5016JDA, Argentina
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Córdoba, Córdoba Province, X5016KEH, Argentina
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CABA, C1181ACH, Argentina
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CABA, C1426ABP, Argentina
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Santa Fe, S3000EPV, Argentina
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Westmead, New South Wales, 2145, Australia
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Woolloongabba, Queensland, 4102, Australia
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Adelaide, South Australia, 5000, Australia
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Parkville, Victoria, 3065, Australia
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St Albans, Victoria, 3021, Australia
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Roeselare, West-Vlaanderen, 8800, Belgium
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Edegem, 2650, Belgium
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Leuven, 3000, Belgium
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Belo Horizonte, Minas Gerais, 30150-221, Brazil
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Curitiba, Paraná, 80440-020, Brazil
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Porto Alegre, Rio Grande do Sul, 90035-074, Brazil
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São Paulo, São Paulo, 04038-002, Brazil
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São Paulo, São Paulo, 05403 000, Brazil
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Sao Jose Rio Preto, 15090 000, Brazil
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Oshawa, Ontario, L1G 2B9, Canada
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Temuco, 4781151, Chile
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Beijing, Beijing Municipality, 100013, China
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Beijing, Beijing Municipality, 102218, China
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Guangzhou, Guangdong, 510030, China
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Guangzhou, Guangdong, 510630, China
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Shenzhen, Guangdong, 518000, China
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Luoyang, Henan, 471003, China
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Zhengzhou, Henan, 450003, China
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Changsha, Hunan, 410011, China
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Changchun, Jilin, 130041, China
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Yinchuan, Ningxia, 750004, China
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Taiyuan, Shanxi, 030001, China
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Xian, Shanxi, 710061, China
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Ürümqi, Xinjiang, 830001, China
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Hangzhou, Zhejiang, 310003, China
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Ningbo, Zhejiang, 315016, China
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Wenzhou, Zhejiang, 325000, China
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Beijing, 100029, China
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Beijing, 100034, China
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Guangzhou, 510080, China
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Ningbo, 315010, China
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Qingdao, 266000, China
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Shanghai, 200025, China
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Shanghai, 200040, China
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Shenzhen, 518036, China
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Medellín, Antioquia, 050001, Colombia
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Barranquilla, Atlántico, 080020, Colombia
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Prague, 128 08, Czechia
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Aalborg, 9000, Denmark
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Arhus N, DK-8200, Denmark
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Copenhagen, DK-2100, Denmark
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Odense C, 5000, Denmark
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Marseille, 13005, France
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Montpellier, 34295, France
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Paris, 75015, France
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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany
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Stuttgart, Baden-Wurttemberg, 70376, Germany
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Göttingen, Lower Saxony, 37075, Germany
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Dresden, Saxony, 01307, Germany
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Aachen, 52074, Germany
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Berlin, 13353, Germany
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Essen, 45147, Germany
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Hanover, 30625, Germany
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Kiel, 24105, Germany
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Magdeburg, 39120, Germany
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Mainz, 55131, Germany
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Tübingen, 72076, Germany
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Ulm, 89081, Germany
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Pécs, Baranya, 7623, Hungary
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Debrecen, Hajdu Bihar Megye, 4032, Hungary
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Szeged, 6725, Hungary
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Bangalore, Karnataka, 560004, India
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New Delhi, National Capital Territory of Delhi, 110017, India
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New Delhi, National Capital Territory of Delhi, 110029, India
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Hyderabad, Telangana, 500082, India
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Ashkelon, 7830604, Israel
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Jerusalem, 9112001, Israel
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Petah Tikva, 4941492, Israel
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Bologna, BO, 40138, Italy
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Naples, 80131, Italy
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Kasugai, Aichi-ken, 486-8510, Japan
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Toyoake, Aichi-ken, 470 1192, Japan
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Toyota, Aichi-ken, 471-8513, Japan
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Sapporo, Hokkaido, 060-8604, Japan
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Sapporo, Hokkaido, 68555, Japan
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Kawasaki, Kanagawa, 213-8587, Japan
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Yokohama, Kanagawa, 224-8503, Japan
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Yokohama, Kanagawa-ku, 236-0004, Japan
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Kyoto, Kyoto, 605-0981, Japan
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Matsumoto, Nagano, 3908621, Japan
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Osaka, Osaka, 5340021, Japan
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Ōmihachiman, Shiga, 523-0082, Japan
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Chiba, 2608712, Japan
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Niigata, 9518520, Japan
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Okayama, 7008558, Japan
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Osaka, 5300012, Japan
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Kuala Lumpur, Kuala Lumpur, 50586, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Mexicali, Baja California Norte, 21200, Mexico
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Mexico City, 03100, Mexico
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Querétaro, 76000, Mexico
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Groningen, Provincie Groningen, 9713 GZ, Netherlands
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Nordbyhagen, Oslo County, 1478, Norway
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Bergen, NO-5021, Norway
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Omsk, 644112, Russia
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Rostov-on-Don, 344022, Russia
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Saint Petersburg, 197110, Russia
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Singapore, 119074, Singapore
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Singapore, 169608, Singapore
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Košice, Slovakia, 040 11, Slovakia
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Maribor, Slovenia, 2000, Slovenia
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Ljubljana, 1000, Slovenia
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Bloemfontein, Free State, 9301, South Africa
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Bundang Gu, Gyeonggi-do, 13620, South Korea
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Seoul, Korea, 02841, South Korea
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Seoul, Korea, 03080, South Korea
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Seoul, Korea, 03312, South Korea
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Cheongju-si, North Chungcheong, 28644, South Korea
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Busan, 47392, South Korea
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Seoul, 03722, South Korea
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Seoul, 06591, South Korea
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Seoul, 06973, South Korea
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Seoul, 134 727, South Korea
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Taegu, 41944, South Korea
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Pamplona, Navarre, 31008, Spain
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Barcelona, 08036, Spain
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Salamanca, 37007, Spain
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Seville, 41013, Spain
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Danderyd, 182 88, Sweden
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Stockholm, 141 86, Sweden
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Kaohsiung City, 83301, Taiwan
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New Taipei City, 22060, Taiwan
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New Taipei City, 23561, Taiwan
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Taichung, 40447, Taiwan
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Taipei, 10002, Taiwan
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Taoyuan District, 33305, Taiwan
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Istanbul, Fatih, 34093, Turkey (Türkiye)
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Istanbul, Fatih, 34098, Turkey (Türkiye)
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Köseköy, Kocaeli, 41380, Turkey (Türkiye)
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Antalya, Konyaalti, 07070, Turkey (Türkiye)
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Kayseri, Melikgazi, 38039, Turkey (Türkiye)
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Istanbul, Sariyer, 34396, Turkey (Türkiye)
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Istanbul, Sultangazi, 34265, Turkey (Türkiye)
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Ankara, Yenimahalle, 06500, Turkey (Türkiye)
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Mersin, Yenisehir, 33110, Turkey (Türkiye)
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Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom
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Leicester, LE5 4PW, United Kingdom
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London, SE5 9RS, United Kingdom
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London, SW17 0QT, United Kingdom
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Salford, M6 8HD, United Kingdom
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Ho Chi Minh City, VNM, 700000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
Related Publications (6)
Barratt J, Eren N, Kashihara N, Maes B, Rizk DV, Rovin B, Trimarchi H, Zhang H, Wang W, Kocyigit I, Hao C, Tesar V, Turgutalp K, Yang L, Xing G, Duro Garcia V, Han SH, Lu W, Pisani A, Weinmann-Menke J, Eitner F, Guerard N, Butylin D, Monaco L, Scosyrev E, Magirr A, Renfurm R, Hach T, Perkovic V; APPLAUSE-IgAN Study Group. Iptacopan in IgA Nephropathy - Final 24-Month Data. N Engl J Med. 2026 Mar 29. doi: 10.1056/NEJMoa2600743. Online ahead of print.
PMID: 41910396DERIVEDPerkovic V, Barratt J, Rovin B, Kashihara N, Maes B, Zhang H, Trimarchi H, Kollins D, Papachristofi O, Jacinto-Sanders S, Merkel T, Guerard N, Renfurm R, Hach T, Rizk DV; APPLAUSE-IgAN Investigators. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N Engl J Med. 2025 Feb 6;392(6):531-543. doi: 10.1056/NEJMoa2410316. Epub 2024 Oct 25.
PMID: 39453772DERIVEDTunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.
PMID: 38299639DERIVEDZhang H, Rizk DV, Perkovic V, Maes B, Kashihara N, Rovin B, Trimarchi H, Sprangers B, Meier M, Kollins D, Papachristofi O, Milojevic J, Junge G, Nidamarthy PK, Charney A, Barratt J. Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int. 2024 Jan;105(1):189-199. doi: 10.1016/j.kint.2023.09.027. Epub 2023 Oct 31.
PMID: 37914086DERIVEDEl Karoui K, Fervenza FC, De Vriese AS. Treatment of IgA Nephropathy: A Rapidly Evolving Field. J Am Soc Nephrol. 2024 Jan 1;35(1):103-116. doi: 10.1681/ASN.0000000000000242. Epub 2023 Sep 29.
PMID: 37772889DERIVEDReich HN, Floege J. How I Treat IgA Nephropathy. Clin J Am Soc Nephrol. 2022 Aug;17(8):1243-1246. doi: 10.2215/CJN.02710322. Epub 2022 Jun 8. No abstract available.
PMID: 35675911DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
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
September 9, 2020
First Posted
October 8, 2020
Study Start
January 25, 2021
Primary Completion
September 19, 2025
Study Completion
September 19, 2025
Last Updated
December 23, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com