IgA NephropathyPhase 3APPLAUSE-IgANNCT04578834
Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
A Phase 3 study testing LNP023 in people with IgA Nephropathy, run by Novartis Pharmaceuticals at 177 sites in 35 countries.
Trial summary
The study was 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- IgA Nephropathy
- What is being tested?
- LNP023
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 517 participants
- Where
- 177 sitesin 35 countries
- Study dates
- 25 Jan 2021to 19 Sep 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
177 sites in 35 countries.
177 sites in 35 countries
China24 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100013
Novartis Investigative Site
Beijing, Beijing Municipality, 102218
Novartis Investigative Site
Beijing, 100029
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Changchun, Jilin, 130041
Novartis Investigative Site
Changsha, Hunan, 410011
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Novartis Investigative Site
Guangzhou, Guangdong, 510630
Novartis Investigative Site
Guangzhou, 510080
Novartis Investigative Site
Hangzhou, Zhejiang, 310003
Novartis Investigative Site
Luoyang, Henan, 471003
Novartis Investigative Site
Ningbo, Zhejiang, 315016
Novartis Investigative Site
Ningbo, 315010
Novartis Investigative Site
Qingdao, 266000
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shanghai, 200040
Novartis Investigative Site
Shenzhen, Guangdong, 518000
Novartis Investigative Site
Shenzhen, 518036
Novartis Investigative Site
Taiyuan, Shanxi, 030001
Novartis Investigative Site
Ürümqi, Xinjiang, 830001
Novartis Investigative Site
Wenzhou, Zhejiang, 325000
Novartis Investigative Site
Xian, Shanxi, 710061
Novartis Investigative Site
Yinchuan, Ningxia, 750004
Novartis Investigative Site
Zhengzhou, Henan, 450003
United States22 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Anschutz
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Renal Associates of Baton Rouge
Baton Rouge, Louisiana, 70808
Boise Kidney and Hypertension
Boise, Idaho, 83706
Brigham and Womens Hosp Harvard Med School
Boston, Massachusetts, 02115
CaRe Research
Chubbuck, Idaho, 83202
Dallas Renal Group
Dallas, Texas, 75230
AZ Kidney Dise and Hypertension Ctr
Glendale, Arizona, 85306
Nep Assoc of Northern Illinois
Hinsdale, Illinois, 60521
Prolato Clinical Research Center
Houston, Texas, 77054
New Jersey Kidney Care
Jersey City, New Jersey, 07305
Clin Rsrch Consult a JCCT Company
Kansas City, Missouri, 64112
DaVita Clinical Research
Las Vegas, Nevada, 89146
UCLA Medical Center
Los Angeles, California, 90095
Columbia University Irving Medical
New York, New York, 10032
Nephrology Associates PA
Newark, Delaware, 19713
AKDHC Medical Research ServicesLLC
Phoenix, Arizona, 85016
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Kaiser Permanente
San Diego, California, 92111
North America Research Institute
San Dimas, California, 91773
Univ of Washington Medi Cen
Seattle, Washington, 98104
Japan16 sites
Novartis Investigative Site
Chiba, 2608712
Novartis Investigative Site
Kasugai, Aichi-ken, 4868510
Novartis Investigative Site
Kawasaki, Kanagawa, 2138587
Novartis Investigative Site
Kyoto, Kyoto, 6050981
Novartis Investigative Site
Matsumoto, Nagano, 3908621
Novartis Investigative Site
Niigata, 9518520
Novartis Investigative Site
Okayama, 7008558
Novartis Investigative Site
Ōmihachiman, Shiga, 5230082
Novartis Investigative Site
Osaka, Osaka, 5340021
Novartis Investigative Site
Osaka, 5300012
Novartis Investigative Site
Sapporo, Hokkaido, 0068555
Novartis Investigative Site
Sapporo, Hokkaido, 0608604
Novartis Investigative Site
Toyoake, Aichi-ken, 4701192
Novartis Investigative Site
Toyota, Aichi-ken, 4718513
Novartis Investigative Site
Yokohama, Kanagawa, 2248503
Novartis Investigative Site
Yokohama, Kanagawa, 2360004
Germany13 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Novartis Investigative Site
Göttingen, Lower Saxony, 37075
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Stuttgart, Baden-Wurttemberg, 70376
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Ulm, 89081
South Korea11 sites
Novartis Investigative Site
Bundang Gu, Gyeonggi-do, 13620
Novartis Investigative Site
Busan, 47392
Novartis Investigative Site
Cheongju-si, North Chungcheong, 28644
Novartis Investigative Site
Seoul, Korea, 02841
Novartis Investigative Site
Seoul, Korea, 03312
Novartis Investigative Site
Seoul, Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 05278
Novartis Investigative Site
Seoul, 06591
Novartis Investigative Site
Seoul, 06973
Novartis Investigative Site
Taegu, 41944
Turkey (Türkiye)9 sites
Novartis Investigative Site
Ankara, Yenimahalle, 06500
Novartis Investigative Site
Antalya, Konyaalti, 07070
Novartis Investigative Site
Istanbul, Fatih, 34093
Novartis Investigative Site
Istanbul, Fatih, 34098
Novartis Investigative Site
Istanbul, Sariyer, 34396
Novartis Investigative Site
Istanbul, Sultangazi, 34265
Novartis Investigative Site
Kayseri, Melikgazi, 38039
Novartis Investigative Site
Köseköy, Kocaeli, 41380
Novartis Investigative Site
Mersin, Yenisehir, 33110
Brazil6 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-221
Novartis Investigative Site
Curitiba, Paraná, 80440-020
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-074
Novartis Investigative Site
São José do Rio Preto, São Paulo, 15090 000
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
Taiwan6 sites
Novartis Investigative Site
Kaohsiung City, 833
Novartis Investigative Site
New Taipei City, 22060
Novartis Investigative Site
New Taipei City, 23561
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taoyuan, 33305
Argentina5 sites
Novartis Investigative Site
CABA, C1181ACH
Novartis Investigative Site
CABA, C1426ABP
Novartis Investigative Site
Córdoba, Córdoba Province, X5016JDA
Novartis Investigative Site
Córdoba, Córdoba Province, X5016KEH
Novartis Investigative Site
Santa Fe, S3000EPV
Australia5 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Parkville, Victoria, 3065
Novartis Investigative Site
St Albans, Victoria, 3021
Novartis Investigative Site
Westmead, New South Wales, 2145
Novartis Investigative Site
Woolloongabba, Queensland, 4102
United Kingdom5 sites
Novartis Investigative Site
Leicester, LE5 4PW
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
London, SW17 0QT
Novartis Investigative Site
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
Novartis Investigative Site
Salford, M6 8HD
Denmark4 sites
Novartis Investigative Site
Aalborg, 9000
Novartis Investigative Site
Arhus N, 8200
Novartis Investigative Site
Copenhagen, 2100
Novartis Investigative Site
Odense C, 5000
India4 sites
Novartis Investigative Site
Bangalore, Karnataka, 560004
Novartis Investigative Site
Hyderabad, Telangana, 500082
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110017
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110029
Spain4 sites
Novartis Investigative Site
Barcelona, 08036
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Salamanca, 37007
Novartis Investigative Site
Seville, 41013
Belgium3 sites
Novartis Investigative Site
Edegem, 2650
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Roeselare, West Vlaanderen, 8800
France3 sites
Novartis Investigative Site
Marseille, 13005
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Paris, 75015
Hungary3 sites
Novartis Investigative Site
Debrecen, Hajdu Bihar Megye, 4032
Novartis Investigative Site
Pécs, Baranya, 7623
Novartis Investigative Site
Szeged, 6725
Israel3 sites
Novartis Investigative Site
Ashkelon, 7830604
Novartis Investigative Site
Jerusalem, 9112001
Novartis Investigative Site
Petah Tikva, 4941492
Mexico3 sites
Novartis Investigative Site
Benito Juárez, Mexico City, 03100
Novartis Investigative Site
Mexicali, Baja California Norte, 21200
Novartis Investigative Site
Querétaro, 76000
Russia3 sites
Novartis Investigative Site
Omsk, 644112
Novartis Investigative Site
Rostov-on-Don, 344022
Novartis Investigative Site
Saint Petersburg, 197110
Thailand3 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Colombia2 sites
Novartis Investigative Site
Barranquilla, Atlántico, 080020
Novartis Investigative Site
Medellín, Antioquia, 050001
Italy2 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Naples, 80131
Malaysia2 sites
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Novartis Investigative Site
Kuala Lumpur, 59100
Norway2 sites
Novartis Investigative Site
Bergen, NO-5021
Novartis Investigative Site
Nordbyhagen, Oslo, 1478
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 169608
Slovenia2 sites
Novartis Investigative Site
Ljubljana, 1000
Novartis Investigative Site
Maribor, Slovenia, 2000
Sweden2 sites
Novartis Investigative Site
Danderyd, 182 88
Novartis Investigative Site
Stockholm, 141 86
Vietnam2 sites
Novartis Investigative Site
Ho Chi Minh City, VNM, 700000
Novartis Investigative Site
Ho Chi Minh City, 700000
Netherlands1 site
Novartis Investigative Site
Groningen, Provincie Groningen, 9713 GZ
South Africa1 site
Novartis Investigative Site
Bloemfontein, Free State, 9301
About this study
Official title: 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
The study was 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.
Read the detailed description
The purpose of the study was to evaluate the efficacy and safety of iptacopan (LNP023) compared to placebo on proteinuria reduction and slowing disease progression in primary IgAN patients. This study served as the pivotal trial supporting the registration of iptacopan in IgA Nephropathy patients with the aim to demonstrate a clinically meaningful reduction in in eGFR slope decline and reduction in proteinuria. The trial continued in a blinded fashion to confirm long-term efficacy based on annualized total slope of eGFR decline over 24 months to provide confirmatory evidence of LNP023 efficacy and safety in treating patients with IgAN. The trial planned to enroll approximately 470 participants; 430 biopsy-proven IgAN participants with eGFR ≥30 mL /min/1.73m2 (main study population) and up to approximately 40 participants with eGFR 20 to <30 mL/min/1.73m2 (severe renal impairment (SRI) population).
- Conditions
- IgA Nephropathy
- Being tested
- Placebo, LNP023
- Keywords
- LNP023, IgA nephropathy, IgAN, proteinuria, UPCR, eGFR, eGFR slope, kidney function decline
- Medical subject headings
- Glomerulonephritis, IGA, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo to LNP023 200mg b.i.d
LNP023Drug
Also called iptacopan
LNP023 200mg b.i.d
| Study group | Role | What they receive |
|---|---|---|
| LNP023 200mg b.i.d | Experimental | Not described Receives: Drug: LNP023 |
| Placebo to LNP023 200mg b.i.d | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio to Baseline in UPCR at 9 Months - Interim Analysis
Evaluated at interim analysis - Ratio to baseline in Urine Protein to Creatinine Ratio (UPCR), sampled from 24h urine collection, at 9 months.
Ratio being: UPCR at 9 months in g/g divided by UPCR at Baseline in g/g. Lower values correspond to better outcomes.
Measured: Baseline and 9 months
Annualized Total eGFR Slope Estimated Over 24 Months - Final Analysis
Evaluated at final analysis - Annualized total eGFR slope over 24 months, expressed as the rate of change in estimated glomerular filtration rate (eGFR). eGFR is a measure of kidney function and was calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula. A negative slope indicates declining kidney function. A less negative slope indicates a slower decline in kidney function and therefore a more favorable outcome.
Measured: 24 months
Secondary outcomes (12)
Change From Baseline in eGFR at 9 Months - Interim Analysis
Evaluated at interim analysis - Change from baseline in estimated glomerular filtration rate (eGFR) at 9 months
Measured: Baseline and 9 months
Proportion of Participants Reaching Proteinuria < 1 g/g of UPCR 24h at 9 Months - Interim Analysis
Evaluated at interim analysis - Proportion of participants reaching proteinuria < 1 g/g of Urine Protein-To-Creatinine Ratio (UPCR) sampled from 24-hour urine collection at 9 months, without receiving Corticosteroids/Immunosuppressant (CS/IS) or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating Kidney Replacement Therapy (KRT). Marginal proportion can be interpreted as the population average probability of being a responder in each treatment group.
Measured: Baseline and 9 months
Annualized Total eGFR Slope Estimated Over 12 Months - Interim Analysis
Evaluated at interim analysis -Annualized total eGFR slope over 12 months, expressed as the rate of change in estimated glomerular filtration rate (eGFR). eGFR is a measure of kidney function. A negative slope indicates declining kidney function. A less negative slope indicates a slower decline in kidney function and therefore a more favorable outcome.
Measured: 12 months
Change From Baseline in the FACIT-Fatigue Total Score to 9 Months - Interim Analysis
Evaluated at interim analysis -Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue scale (version 4), is a 13-item questionnaire that assesses patient-perceived tiredness, weakness and difficulty conducting activities due to fatigue. The purpose of FACIT-Fatigue in this study was to assess the experience and impact of fatigue on participants with IgAN.
Score ranges from 0 to 52, with higher scores indicating less fatigue.
Measured: Baseline and 9 months
Number of Participants With Adverse Events in the Main Study Population During the On-treatment Period - Interim Analysis
Number of participants with treatment-emergent Adverse Events, including clinically significant abnormal safety laboratory parameters and vital signs during the on-treatment period.
The on-treatment period lasts from the date of first administration of study treatment to 7 days after the date of the last actual administration of any study treatment
Measured: Up to 24 months
Number of Participants With Adverse Events in the SRI Population During the On-treatment Period - Interim Analysis
Number of participants with treatment-emergent Adverse Events, including clinically significant abnormal safety laboratory parameters and vital signs during the on-treatment period.
The on-treatment period lasts from the date of first administration of study treatment to 7 days after the date of the last actual administration of any study treatment
Measured: Up to 24 months
Ratio to Baseline in UPCR at 9 Months - Final Analysis
Evaluated at final analysis - Ratio to baseline in Urine Protein to Creatinine Ratio (UPCR), sampled from 24h urine collection, at 9 months.
Ratio being: UPCR at 9 months in g/g divided by UPCR at Baseline in g/g. Lower values correspond to better outcomes.
In line with the testing strategy, this endpoint was not tested at the final analysis.
Measured: Baseline and 9 months
Proportion of Participants Reaching Proteinuria < 1 g/g of UPCR 24h at 9 Months - Final Analysis
Evaluated at final analysis - Proportion of participants reaching proteinuria < 1 g/g of Urine Protein-To-Creatinine Ratio (UPCR) 24h at 9 months, without receiving Corticosteroids/Immunosuppressant (CS/IS) or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating Kidney Replacement Therapy (KRT). Marginal proportion can be interpreted as the population average probability of being a responder in each treatment group.
Measured: Baseline and 9 months
Time to First Occurrence of Composite Kidney Failure Endpoint Event - Final Analysis
Evaluated at final analysis - Time to first occurrence of composite kidney failure endpoint, defined as a sustained decline in the eGFR of at least 30% from baseline for at least 4 weeks, a sustained eGFR of less than 15 mL/min/1.73m2 for at least 4 weeks, initiation of maintenance dialysis (defined as dialysis for a period of ≥4 weeks) or death from kidney failure.
For clarity: Please note that the number of patients with a composite kidney failure endpoint event is presented with statistical analysis of the time to composite kidney failure endpoint event.
Measured: Up to 24 months
Change From Baseline in the FACIT-Fatigue Total Score to 9 Months - Final Analysis
Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue scale (version 4), is a 13-item questionnaire that assesses patient-perceived tiredness, weakness and difficulty conducting activities due to fatigue. The purpose of FACIT-Fatigue in this study was to assess the experience and impact of fatigue on participants with IgAN.
Score ranges from 0 to 52, with higher scores indicating less fatigue.
Measured: Baseline and Month 9
Number of Participants With Adverse Events in the Main Study Population During the On-treatment Period - Final Analysis
Number of participants with treatment-emergent Adverse Events, including clinically significant abnormal safety laboratory parameters and vital signs during the on-treatment period.
The on-treatment period lasts from the date of first administration of study treatment to 7 days after the date of the last actual administration of any study treatment
Measured: Up to 24 months
Number of Participants With Adverse Events in the SRI Population During the On-treatment Period- Final Analysis
Number of participants with treatment-emergent Adverse Events, including clinically significant abnormal safety laboratory parameters and vital signs during the on-treatment period.
The on-treatment period lasts from the date of first administration of study treatment to 7 days after the date of the last actual administration of any study treatment
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start25 Jan 2021
- Primary completion19 Sep 2025
- Study completion19 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for IgA NephropathyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04578834
- Sponsor's protocol ID
- CLNP023A2301
- Other IDs
- 2024-511067-29-00
- Acronym
- APPLAUSE-IgAN
- Status last verified
- Oct 2026
- First submitted
- 9 Sep 2020
- Last updated
- 4 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Rovin BH, Trimarchi H, Maes B, Perkovic V, Kashihara N, Zhang H, Barratt J, Cheng H, Lee H, Lee SH, Lim SK, Raju SB, Satirapoj B, Seyahi N, Tian YC, Wu CH, Xiong ZY, Xue H, Yee SY, Petrovic-Bulatovic K, Attari Z, Butylin D, Jacinto-Sanders S, Pletscher M, Magirr A, Renfurm R, Hach T, Rizk DV. Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy. Kidney Int. 2026 Oct 22:S0085-2538(26)00826-4. doi: 10.1016/j.kint.2026.09.017. Online ahead of print.
PubMed 42909451Barratt 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 Jul 30;395(5):465-477. doi: 10.1056/NEJMoa2600743. Epub 2026 Mar 29.
PubMed 41910396Howie AJ, Lalayiannis AD. The Oxford Classification Should Remain the Gold Standard for Classification of IgA Nephropathy: CON. Kidney360. 2026 Oct 1;7(10):2382-2384. doi: 10.34067/KID.0000001083. Epub 2026 Feb 9. No abstract available.
PubMed 41661687Perkovic 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.
PubMed 39453772Tunnicliffe 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.
PubMed 38299639Zhang 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.
PubMed 37914086El 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.
PubMed 37772889Reich 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.
PubMed 35675911
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04578834
- Acronym / sponsor ID
- APPLAUSE-IgAN / CLNP023A2301
- Conditions
- IgA Nephropathy
- Keywords
- LNP023, IgA nephropathy, IgAN, proteinuria, UPCR, eGFR, eGFR slope, kidney function decline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2021 (actual)
- Primary completion
- 19 Sep 2025 (actual)
- Study completion
- 19 Sep 2025 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Posted 4 Nov 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study was 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.
Detailed description
The purpose of the study was to evaluate the efficacy and safety of iptacopan (LNP023) compared to placebo on proteinuria reduction and slowing disease progression in primary IgAN patients. This study served as the pivotal trial supporting the registration of iptacopan in IgA Nephropathy patients with the aim to demonstrate a clinically meaningful reduction in in eGFR slope decline and reduction in proteinuria. The trial continued in a blinded fashion to confirm long-term efficacy based on annualized total slope of eGFR decline over 24 months to provide confirmatory evidence of LNP023 efficacy and safety in treating patients with IgAN. The trial planned to enroll approximately 470 participants; 430 biopsy-proven IgAN participants with eGFR ≥30 mL /min/1.73m2 (main study population) and up to approximately 40 participants with eGFR 20 to <30 mL/min/1.73m2 (severe renal impairment (SRI) population).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LNP023 200mg b.i.d | Experimental | Drug: LNP023 |
| Placebo to LNP023 200mg b.i.d | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo to LNP023 200mg b.i.d | Drug | Placebo to LNP023 200mg b.i.d |
| LNP023Also: iptacopanLNP023 200mg b.i.d | Drug | LNP023 200mg b.i.d |
Primary outcome
Ratio to Baseline in UPCR at 9 Months - Interim Analysis
Time frame: Baseline and 9 months
Evaluated at interim analysis - Ratio to baseline in Urine Protein to Creatinine Ratio (UPCR), sampled from 24h urine collection, at 9 months. Ratio being: UPCR at 9 months in g/g divided by UPCR at Baseline in g/g. Lower values correspond to better outcomes.
Annualized Total eGFR Slope Estimated Over 24 Months - Final Analysis
Time frame: 24 months
Evaluated at final analysis - Annualized total eGFR slope over 24 months, expressed as the rate of change in estimated glomerular filtration rate (eGFR). eGFR is a measure of kidney function and was calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula. A negative slope indicates declining kidney function. A less negative slope indicates a slower decline in kidney function and therefore a more favorable outcome.
12 secondary outcomes
Change From Baseline in eGFR at 9 Months - Interim Analysis
Time frame: Baseline and 9 months
Proportion of Participants Reaching Proteinuria < 1 g/g of UPCR 24h at 9 Months - Interim Analysis
Time frame: Baseline and 9 months
Annualized Total eGFR Slope Estimated Over 12 Months - Interim Analysis
Time frame: 12 months
Change From Baseline in the FACIT-Fatigue Total Score to 9 Months - Interim Analysis
Time frame: Baseline and 9 months
Number of Participants With Adverse Events in the Main Study Population During the On-treatment Period - Interim Analysis
Time frame: Up to 24 months
Number of Participants With Adverse Events in the SRI Population During the On-treatment Period - Interim Analysis
Time frame: Up to 24 months
Ratio to Baseline in UPCR at 9 Months - Final Analysis
Time frame: Baseline and 9 months
Proportion of Participants Reaching Proteinuria < 1 g/g of UPCR 24h at 9 Months - Final Analysis
Time frame: Baseline and 9 months
Time to First Occurrence of Composite Kidney Failure Endpoint Event - Final Analysis
Time frame: Up to 24 months
Change From Baseline in the FACIT-Fatigue Total Score to 9 Months - Final Analysis
Time frame: Baseline and Month 9
Number of Participants With Adverse Events in the Main Study Population During the On-treatment Period - Final Analysis
Time frame: Up to 24 months
Number of Participants With Adverse Events in the SRI Population During the On-treatment Period- Final Analysis
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42909451Rovin BH, Trimarchi H, Maes B, Perkovic V, Kashihara N, Zhang H, Barratt J, Cheng H, Lee H, Lee SH, Lim SK, Raju SB, Satirapoj B, Seyahi N, Tian YC, Wu CH, Xiong ZY, Xue H, Yee SY, Petrovic-Bulatovic K, Attari Z, Butylin D, Jacinto-Sanders S, Pletscher M, Magirr A, Renfurm R, Hach T, Rizk DV. Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy. Kidney Int. 2026 Oct 22:S0085-2538(26)00826-4. doi: 10.1016/j.kint.2026.09.017. Online ahead of print.
- Derived from this study: PubMed 41910396Barratt 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 Jul 30;395(5):465-477. doi: 10.1056/NEJMoa2600743. Epub 2026 Mar 29.
- Derived from this study: PubMed 41661687Howie AJ, Lalayiannis AD. The Oxford Classification Should Remain the Gold Standard for Classification of IgA Nephropathy: CON. Kidney360. 2026 Oct 1;7(10):2382-2384. doi: 10.34067/KID.0000001083. Epub 2026 Feb 9. No abstract available.
- Derived from this study: PubMed 39453772Perkovic 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.
- Derived from this study: PubMed 38299639Tunnicliffe 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.
- Derived from this study: PubMed 37914086Zhang 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.
- Derived from this study: PubMed 37772889El 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.
- Derived from this study: PubMed 35675911Reich 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
177 sites in 35 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LNP023 in people with IgA Nephropathy, run by Novartis Pharmaceuticals at 177 sites in 35 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in China, United States, Japan, Germany, South Korea and 30 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio to Baseline in UPCR at 9 Months - Interim Analysis (time frame: Baseline and 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04578834, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.