Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation

An Adaptive Seamless Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients

ClinicalTrials.gov Identifier: NCT03373461

Novartis Reference Number: CLNP023X2203

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

Efficacy and safety of LNP023 in IgAN patients

Condition 
IgA Nephropathy
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
146 participants
Start date 
Feb 07, 2018
Completion date 
Jun 29, 2021
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
LNP023
LNP023 b.i.d. Dose 1, Dose 2 and Dose 3
Drug
Placebo
Placebo to LPN023 b.i.d

Eligibility Criteria

Inclusion Criteria:

Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years.
Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / [Height (m)]2
Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2
Urine protein ≥1 g/24hr at screening and ≥0.75 g / 24h after the run- in period
Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023
All patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB therapy for the individual, antihypertensive therapy or diuretics for at least 90 days before dosing

Exclusion criteria

Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing
Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
All transplanted patients (any organ, including bone marrow)

History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result.

Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a patient. Patients with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded

Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following:

A history of invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
Splenectomy
Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including rectal bleeding;
Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
Pancreatic injury or pancreatitis;
Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested.
Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed 3 x upper limit of normal (ULN)
PT/INR must be within the reference range of normal individuals
Evidence of urinary obstruction or difficulty in voiding any urinary tract disorder other than IgNA that is associated with hematuria at screening and before dosing; [If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error]
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline:

PR > 200 msec
QRS complex > 120 msec
QTcF > 450 msec (males)
QTcF > 460 msec (females)
History of familial long QT syndrome or known family history of Torsades de Pointes
Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
History of severe allergic reactions as per Investigator decision
Plasma donation (> 200mL) within 30 days prior to first dosing.
Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug. Highly effective contraception methods include:

Total abstinence from heterosexual intercourse (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure <1%), for example hormone vaginal ring or transdermal hormone contraception In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.

If local regulations deviate from the contraception methods listed above and require more extensive measures to prevent pregnancy, local regulations apply and will be described in the ICF.

Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
History of any porphyria metabolic disorder
History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline.
History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes

Study Locations

United States
Novartis Investigative Site
Withdrawn
Florence, 35630
Alabama
United States
Novartis Investigative Site
Withdrawn
Ann Arbor, 48109
Michigan
United States
Novartis Investigative Site
Withdrawn
Temple, 76502
Texas
United States
Argentina
Novartis Investigative Site
Recruiting
Caba, C1181ACH
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Caba, C1280AEB
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Ciudad Autonoma de Bs As, C1015ABO
-
Argentina
Australia
Novartis Investigative Site
Recruiting
Westmead, 2145
New South Wales
Australia
Novartis Investigative Site
Recruiting
Parkville, 3050
Victoria
Australia
Belgium
Novartis Investigative Site
Active, not recruiting
Edegem, 2650
Antwerpen
Belgium
Novartis Investigative Site
Active, not recruiting
Leuven, 3000
-
Belgium
Novartis Investigative Site
Active, not recruiting
Roeselare, 8800
-
Belgium
Brazil
Novartis Investigative Site
Active, not recruiting
Curitiba, 80440-020
PR
Brazil
Novartis Investigative Site
Active, not recruiting
Porto Alegre, 90020-090
RS
Brazil
Novartis Investigative Site
Withdrawn
Joinville, 893227-680
Santa Catarina
Brazil
Novartis Investigative Site
Withdrawn
Sao Jose do Rio Preto, 15090 000
-
Brazil
China
Novartis Investigative Site
Withdrawn
Beijing, 100039
Beijing
China
Novartis Investigative Site
Active, not recruiting
Guangzhou, 510080
Guangdong
China
Novartis Investigative Site
Completed
Beijing, 100034
-
China
Novartis Investigative Site
Active, not recruiting
Guang Zhou, 510080
-
China
Novartis Investigative Site
Active, not recruiting
Shanghai, 200040
-
China
Colombia
Novartis Investigative Site
Active, not recruiting
Barranquilla,
-
Colombia
Novartis Investigative Site
Recruiting
Bogota, 110231
-
Colombia
Czechia
Novartis Investigative Site
Withdrawn
Prague 4, 140 21
-
Czechia
Novartis Investigative Site
Active, not recruiting
Praha, 12808
-
Czechia
Denmark
Novartis Investigative Site
Completed
Aalborg, 9000
-
Denmark
Novartis Investigative Site
Active, not recruiting
Arhus N, DK-8200
-
Denmark
Finland
Novartis Investigative Site
Completed
HUS, 00029
-
Finland
France
Novartis Investigative Site
Active, not recruiting
Montpellier, 34295
-
France
Germany
Novartis Investigative Site
Active, not recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Withdrawn
Hamburg, 20246
-
Germany
Novartis Investigative Site
Completed
Heidelberg, 69120
-
Germany
Hong Kong
Novartis Investigative Site
Active, not recruiting
Hong Kong SAR,
-
Hong Kong
Hungary
Novartis Investigative Site
Withdrawn
Pecs, 7632
-
Hungary
India
Novartis Investigative Site
Active, not recruiting
New Delhi, 110 017
Delhi
India
Novartis Investigative Site
Recruiting
Bangalore, 560017
Karnataka
India
Novartis Investigative Site
Withdrawn
Mysore, 570001
Karnataka
India
Novartis Investigative Site
Active, not recruiting
New Delhi, 110029
-
India
Israel
Novartis Investigative Site
Active, not recruiting
Ashkelon, 78278
-
Israel
Novartis Investigative Site
Active, not recruiting
Jerusalem, 91120
-
Israel
Novartis Investigative Site
Active, not recruiting
Petach Tikva, 49100
-
Israel
Italy
Novartis Investigative Site
Active, not recruiting
Ranica, 24020
BG
Italy
Novartis Investigative Site
Withdrawn
Napoli, 80100
-
Italy
Japan
Novartis Investigative Site
Active, not recruiting
Toyoake city, 470 1192
Aichi
Japan
Novartis Investigative Site
Active, not recruiting
Sapporo-city, 006-8555
Hokkaido
Japan
Novartis Investigative Site
Withdrawn
Nishinomiya, 663 8501
Hyogo
Japan
Novartis Investigative Site
Withdrawn
Kawasaki-city, 216-8511
Kanagawa
Japan
Novartis Investigative Site
Active, not recruiting
Yokohama-city, 236-0004
Kanagawa
Japan
Novartis Investigative Site
Active, not recruiting
Sendai, 981-8501
Miyagi
Japan
Novartis Investigative Site
Active, not recruiting
Okayama-city, 700-8558
Okayama
Japan
Novartis Investigative Site
Active, not recruiting
Osaka-city, 530-8480
Osaka
Japan
Novartis Investigative Site
Withdrawn
Bunkyo ku, 113-8431
Tokyo
Japan
Novartis Investigative Site
Withdrawn
Bunkyo-ku, 113-8519
Tokyo
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 43000
Selangor Darul Ehsan
Malaysia
Novartis Investigative Site
Active, not recruiting
Kuala Lumpur, 50589
-
Malaysia
Netherlands
Novartis Investigative Site
Completed
Groningen, 9713 GZ
-
Netherlands
Norway
Novartis Investigative Site
Active, not recruiting
Bergen, 5021
-
Norway
Novartis Investigative Site
Active, not recruiting
Loerenskog, NO 1478
-
Norway
Novartis Investigative Site
Completed
Oslo, NO 0450
-
Norway
Singapore
Novartis Investigative Site
Completed
Singapore, 119228
-
Singapore
Novartis Investigative Site
Completed
Singapore, 169608
-
Singapore
Spain
Novartis Investigative Site
Withdrawn
Barcelona, 08025
Catalunya
Spain
Novartis Investigative Site
Withdrawn
Madrid, 28040
-
Spain
Novartis Investigative Site
Withdrawn
Madrid, 28041
-
Spain
Sweden
Novartis Investigative Site
Active, not recruiting
Lund, 221 85
-
Sweden
Novartis Investigative Site
Active, not recruiting
Stockholm, 141 86
-
Sweden
Taiwan
Novartis Investigative Site
Recruiting
New Taipei City, 23561
-
Taiwan
Novartis Investigative Site
Recruiting
Taichung, 40705
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10048
-
Taiwan
Novartis Investigative Site
Recruiting
Taoyuan, 33305
-
Taiwan
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10330
-
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10400
-
Thailand
Novartis Investigative Site
Active, not recruiting
Bangkok, 10400
-
Thailand
Turkey
Novartis Investigative Site
Completed
Istanbul, 34098
TUR
Turkey
Novartis Investigative Site
Active, not recruiting
Ankara, 06100
-
Turkey
Novartis Investigative Site
Active, not recruiting
Kocaeli, 41380
-
Turkey
Novartis Investigative Site
Active, not recruiting
Talas / Kayseri, 38039
-
Turkey
United Kingdom
Novartis Investigative Site
Completed
Cambridge, CB2 0QQ
Cambrigdeshire
United Kingdom
Novartis Investigative Site
Active, not recruiting
Salford, M6 8HD
Manchester
United Kingdom
Novartis Investigative Site
Completed
Leicester, LE5 4PW
-
United Kingdom
Novartis Investigative Site
Completed
London, SE5 9RS
-
United Kingdom
Novartis Investigative Site
Withdrawn
London, W12 0HS
-
United Kingdom
Novartis Investigative Site
Recruiting
London,
-
United Kingdom
Novartis Investigative Site
Recruiting
Newcastle Upon Tyne, NE7 7DN
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]