Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04578834




Registration number
NCT04578834
Ethics application status
Date submitted
9/09/2020
Date registered
8/10/2020
Date last updated
3/05/2024

Titles & IDs
Public title
Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
Scientific 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
Secondary ID [1] 0 0
CLNP023A2301
Universal Trial Number (UTN)
Trial acronym
APPLAUSE-IgAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
IgA Nephropathy 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - LNP023

Experimental: LNP023 200mg b.i.d -

Placebo Comparator: Placebo to LNP023 200mg b.i.d -


Treatment: Drugs: Placebo
Placebo to LNP023 200mg b.i.d

Treatment: Drugs: LNP023
LNP023 200mg b.i.d
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at 9 months
Timepoint [1] 0 0
Baseline and 9 months
Primary outcome [2] 0 0
Annualized total estimated Glomerular Filtration Rate (eGFR) slope over 24 months).
Timepoint [2] 0 0
Baseline and 24 months
Secondary outcome [1] 0 0
Change from baseline in estimated glomerular filtration rate at 9 months
Timepoint [1] 0 0
Baseline and 9 months
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Baseline and 9 months
Secondary outcome [3] 0 0
Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months
Timepoint [3] 0 0
Baseline and 12 months
Secondary outcome [4] 0 0
Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire
Timepoint [4] 0 0
Baseline and 9 months
Secondary outcome [5] 0 0
Time from randomization to first occurrence of composite kidney failure endpoint event
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Ratio to baseline in Urine Protein-To-Creatinine Ratio (sampled from 24h urine collection) at 9 months
Timepoint [6] 0 0
Baseline and 9 months
Secondary outcome [7] 0 0
Proportion of participants reaching Urine Protein-To-Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant Therapy or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating KRT
Timepoint [7] 0 0
Baseline and 9 months
Secondary outcome [8] 0 0
Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.
Timepoint [8] 0 0
Baseline and 9 months

Eligibility
Key inclusion criteria
- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/10/2025
Actual
Sample size
Target
Accrual to date
Final
519
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [3] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [4] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [5] 0 0
Novartis Investigative Site - St Albans
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3065 - Parkville
Recruitment postcode(s) [5] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Argentina
State/province [18] 0 0
Buenos Aires
Country [19] 0 0
Argentina
State/province [19] 0 0
Ciudad Autonoma de Buenos Aire
Country [20] 0 0
Argentina
State/province [20] 0 0
Cordoba
Country [21] 0 0
Argentina
State/province [21] 0 0
Santa Fe
Country [22] 0 0
Belgium
State/province [22] 0 0
Antwerpen
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Roeselare
Country [25] 0 0
Brazil
State/province [25] 0 0
MG
Country [26] 0 0
Brazil
State/province [26] 0 0
PR
Country [27] 0 0
Brazil
State/province [27] 0 0
RS
Country [28] 0 0
Brazil
State/province [28] 0 0
SP
Country [29] 0 0
Brazil
State/province [29] 0 0
Sao Jose do Rio Preto
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Chile
State/province [31] 0 0
Temuco
Country [32] 0 0
China
State/province [32] 0 0
Beijing
Country [33] 0 0
China
State/province [33] 0 0
Guangdong
Country [34] 0 0
China
State/province [34] 0 0
Henan
Country [35] 0 0
China
State/province [35] 0 0
Hunan
Country [36] 0 0
China
State/province [36] 0 0
Jilin
Country [37] 0 0
China
State/province [37] 0 0
Ningxia
Country [38] 0 0
China
State/province [38] 0 0
Shanxi
Country [39] 0 0
China
State/province [39] 0 0
Xinjiang
Country [40] 0 0
China
State/province [40] 0 0
Zhejiang
Country [41] 0 0
China
State/province [41] 0 0
Guang Zhou
Country [42] 0 0
China
State/province [42] 0 0
Ningbo
Country [43] 0 0
China
State/province [43] 0 0
Qingdao
Country [44] 0 0
China
State/province [44] 0 0
Shanghai
Country [45] 0 0
China
State/province [45] 0 0
Shenzhen
Country [46] 0 0
Colombia
State/province [46] 0 0
Antioquia
Country [47] 0 0
Colombia
State/province [47] 0 0
Barranquilla
Country [48] 0 0
Czechia
State/province [48] 0 0
Praha
Country [49] 0 0
Denmark
State/province [49] 0 0
Aalborg
Country [50] 0 0
Denmark
State/province [50] 0 0
Arhus N
Country [51] 0 0
Denmark
State/province [51] 0 0
Copenhagen
Country [52] 0 0
Denmark
State/province [52] 0 0
Odense
Country [53] 0 0
France
State/province [53] 0 0
Marseille
Country [54] 0 0
France
State/province [54] 0 0
Montpellier
Country [55] 0 0
France
State/province [55] 0 0
Paris
Country [56] 0 0
Germany
State/province [56] 0 0
Aachen
Country [57] 0 0
Germany
State/province [57] 0 0
Berlin
Country [58] 0 0
Germany
State/province [58] 0 0
Dresden
Country [59] 0 0
Germany
State/province [59] 0 0
Essen
Country [60] 0 0
Germany
State/province [60] 0 0
Freiburg
Country [61] 0 0
Germany
State/province [61] 0 0
Gottingen
Country [62] 0 0
Germany
State/province [62] 0 0
Hannover
Country [63] 0 0
Germany
State/province [63] 0 0
Kiel
Country [64] 0 0
Germany
State/province [64] 0 0
Magdeburg
Country [65] 0 0
Germany
State/province [65] 0 0
Mainz
Country [66] 0 0
Germany
State/province [66] 0 0
Stuttgart
Country [67] 0 0
Germany
State/province [67] 0 0
Tuebingen
Country [68] 0 0
Germany
State/province [68] 0 0
Ulm
Country [69] 0 0
Hungary
State/province [69] 0 0
Debrecen
Country [70] 0 0
Hungary
State/province [70] 0 0
Pecs
Country [71] 0 0
Hungary
State/province [71] 0 0
Szeged
Country [72] 0 0
India
State/province [72] 0 0
Delhi
Country [73] 0 0
India
State/province [73] 0 0
Karnataka
Country [74] 0 0
India
State/province [74] 0 0
Telangana
Country [75] 0 0
India
State/province [75] 0 0
New Delhi
Country [76] 0 0
Israel
State/province [76] 0 0
Ashkelon
Country [77] 0 0
Israel
State/province [77] 0 0
Jerusalem
Country [78] 0 0
Israel
State/province [78] 0 0
Petach Tikva
Country [79] 0 0
Italy
State/province [79] 0 0
BO
Country [80] 0 0
Italy
State/province [80] 0 0
Napoli
Country [81] 0 0
Japan
State/province [81] 0 0
Aichi
Country [82] 0 0
Japan
State/province [82] 0 0
Chiba
Country [83] 0 0
Japan
State/province [83] 0 0
Hokkaido
Country [84] 0 0
Japan
State/province [84] 0 0
Kanagawa
Country [85] 0 0
Japan
State/province [85] 0 0
Nagano
Country [86] 0 0
Japan
State/province [86] 0 0
Okayama
Country [87] 0 0
Japan
State/province [87] 0 0
Osaka
Country [88] 0 0
Japan
State/province [88] 0 0
Shiga
Country [89] 0 0
Japan
State/province [89] 0 0
Kyoto
Country [90] 0 0
Japan
State/province [90] 0 0
Niigata
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Chungcheongbuk Do
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Gyeonggi Do
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Korea
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Seocho Gu
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Busan
Country [96] 0 0
Korea, Republic of
State/province [96] 0 0
Seoul
Country [97] 0 0
Korea, Republic of
State/province [97] 0 0
Taegu
Country [98] 0 0
Malaysia
State/province [98] 0 0
Kuala Lumpur
Country [99] 0 0
Mexico
State/province [99] 0 0
Baja California Norte
Country [100] 0 0
Mexico
State/province [100] 0 0
Cdmx
Country [101] 0 0
Mexico
State/province [101] 0 0
Queretaro
Country [102] 0 0
Netherlands
State/province [102] 0 0
Groningen
Country [103] 0 0
Norway
State/province [103] 0 0
Oslo
Country [104] 0 0
Norway
State/province [104] 0 0
Bergen
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Omsk
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Rostov On Don
Country [107] 0 0
Russian Federation
State/province [107] 0 0
St. Petersburg
Country [108] 0 0
Singapore
State/province [108] 0 0
Singapore
Country [109] 0 0
Slovakia
State/province [109] 0 0
Kosice
Country [110] 0 0
Slovenia
State/province [110] 0 0
Ljubljana
Country [111] 0 0
Slovenia
State/province [111] 0 0
Maribor
Country [112] 0 0
South Africa
State/province [112] 0 0
Free State
Country [113] 0 0
Spain
State/province [113] 0 0
Andalucia
Country [114] 0 0
Spain
State/province [114] 0 0
Castilla Y Leon
Country [115] 0 0
Spain
State/province [115] 0 0
Catalunya
Country [116] 0 0
Spain
State/province [116] 0 0
Navarra
Country [117] 0 0
Sweden
State/province [117] 0 0
Danderyd
Country [118] 0 0
Sweden
State/province [118] 0 0
Stockholm
Country [119] 0 0
Taiwan
State/province [119] 0 0
Kaohsiung
Country [120] 0 0
Taiwan
State/province [120] 0 0
New Taipei City
Country [121] 0 0
Taiwan
State/province [121] 0 0
New Taipei
Country [122] 0 0
Taiwan
State/province [122] 0 0
Taichung
Country [123] 0 0
Taiwan
State/province [123] 0 0
Taipei
Country [124] 0 0
Taiwan
State/province [124] 0 0
Taoyuan
Country [125] 0 0
Thailand
State/province [125] 0 0
Bangkok
Country [126] 0 0
Turkey
State/province [126] 0 0
Sultangazi
Country [127] 0 0
Turkey
State/province [127] 0 0
TUR
Country [128] 0 0
Turkey
State/province [128] 0 0
Ankara
Country [129] 0 0
Turkey
State/province [129] 0 0
Antalya
Country [130] 0 0
Turkey
State/province [130] 0 0
Istanbul
Country [131] 0 0
Turkey
State/province [131] 0 0
Kocaeli
Country [132] 0 0
Turkey
State/province [132] 0 0
Mersin
Country [133] 0 0
Turkey
State/province [133] 0 0
Talas / Kayseri
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Manchester
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Leicester
Country [136] 0 0
United Kingdom
State/province [136] 0 0
London
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Newcastle Upon Tyne
Country [138] 0 0
Vietnam
State/province [138] 0 0
VNM
Country [139] 0 0
Vietnam
State/province [139] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT04578834
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04578834