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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03373461




Registration number
NCT03373461
Ethics application status
Date submitted
30/11/2017
Date registered
14/12/2017
Date last updated
15/05/2020

Titles & IDs
Public title
Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation
Scientific title
An Adaptive Seamless Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
Secondary ID [1] 0 0
2017-000891-27
Secondary ID [2] 0 0
CLNP023X2203
Universal Trial Number (UTN)
Trial acronym
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 - LNP023
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Placebo to LNP023

Experimental: LNP023 dose 1 - Dose 1 of LNP023

Experimental: LNP023 dose 2 - Dose 2 of LNP023

Experimental: LNP023 dose 3 - Dose 3 of LNP023


Treatment: Drugs: LNP023
LNP023 b.i.d. Dose 1, Dose 2 and Dose 3

Treatment: Drugs: Placebo
Placebo to LPN023 b.i.d

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
change from baseline of urine protein to creatinine concentration - baseline of urine protein to creatinine concentration ratio (UPCR based on 24h urine collection) at 90 days
Timepoint [1] 0 0
Baseline and Day 90
Secondary outcome [1] 0 0
The effect of LNP023 on renal function - Estimated Glomerular Filtration Rate eGFR - eGFR; estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Timepoint [1] 0 0
Baseline, Day 1, 8, 15, 30, 90, 120
Secondary outcome [2] 0 0
The effect of LNP023 on renal function - Serum creatinine - Serum creatinine
Timepoint [2] 0 0
Baseline, Day 1, 8, 15, 30, 90, 120
Secondary outcome [3] 0 0
The effect of LNP023 on renal function - Hematuria - Hematuria (number of erythrocytes/high-power-field (hpf) measured through microscopic examination)
Timepoint [3] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90, 120, 180
Secondary outcome [4] 0 0
The effect of LNP023 on renal function - 24h-UP, 24h-UA, UACR (urine albumin to creatinine concentration ratio) - 24h-UP, 24h-UA, UACR (urine albumin to creatinine concentration ratio)
Timepoint [4] 0 0
Baseline, Day 1, 30, 60, 90, 120, 180
Secondary outcome [5] 0 0
Plasma Pharmacokinetics (PK) of LNP023: Area Under the Plasma Concentration-time Curve (AUC) - AUCtau: Area under the plasma concentration-time curve from time zero to the end of the dosing interval
AUClast: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated as the sum of linear trapezoids using non-compartmental analysis.
Timepoint [5] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90
Secondary outcome [6] 0 0
Observed Maximum Concentration (Cmax) after Drug Administration - Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Timepoint [6] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90
Secondary outcome [7] 0 0
The effect of LNP023 on alternative complement pathway - Bb and sC5b-9
Timepoint [7] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90
Secondary outcome [8] 0 0
To estimate the lowest dose that provides maximal reduction of proteinuria - Ratio to baseline of UPCR urinary prt at the lowest dose that provide
Timepoint [8] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90
Secondary outcome [9] 0 0
Time to Reach the Maximum Plasma Concentration (Tmax) - Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Timepoint [9] 0 0
Baseline, Day 1, 8, 15, 30, 60, 90

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

1. Presence of crescent formation in =50% of glomeruli assessed on renal biopsy

2. 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

3. 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

4. All transplanted patients (any organ, including bone marrow)

5. 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

6. 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]

7. 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.

8. 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

9. History of severe allergic reactions as per Investigator decision

10. Plasma donation (> 200mL) within 30 days prior to first dosing.

11. 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

12. 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.

13. 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

14. History of any porphyria metabolic disorder

15. 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.

16. History of hypersensitivity to any of the study treatments or excipients or to drugs
of similar chemical classes

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
Argentina
State/province [5] 0 0
Ciudad Autonoma de Bs As
Country [6] 0 0
Belgium
State/province [6] 0 0
Antwerpen
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Belgium
State/province [8] 0 0
Roeselare
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
China
State/province [10] 0 0
Guangdong
Country [11] 0 0
China
State/province [11] 0 0
Guang Zhou
Country [12] 0 0
China
State/province [12] 0 0
Shanghai
Country [13] 0 0
Colombia
State/province [13] 0 0
Barranquilla
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague 4
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha
Country [16] 0 0
Denmark
State/province [16] 0 0
Aalborg
Country [17] 0 0
Denmark
State/province [17] 0 0
Arhus N
Country [18] 0 0
Finland
State/province [18] 0 0
HUS
Country [19] 0 0
France
State/province [19] 0 0
Montpellier
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
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Hamburg
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Germany
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Heidelberg
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Hong Kong
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Hong Kong SAR
Country [24] 0 0
Hungary
State/province [24] 0 0
Pecs
Country [25] 0 0
India
State/province [25] 0 0
Delhi
Country [26] 0 0
India
State/province [26] 0 0
Karnataka
Country [27] 0 0
India
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New Delhi
Country [28] 0 0
Israel
State/province [28] 0 0
Ashkelon
Country [29] 0 0
Israel
State/province [29] 0 0
Jerusalem
Country [30] 0 0
Israel
State/province [30] 0 0
Petach Tikva
Country [31] 0 0
Italy
State/province [31] 0 0
BG
Country [32] 0 0
Italy
State/province [32] 0 0
Napoli
Country [33] 0 0
Japan
State/province [33] 0 0
Aichi
Country [34] 0 0
Japan
State/province [34] 0 0
Hokkaido
Country [35] 0 0
Japan
State/province [35] 0 0
Hyogo
Country [36] 0 0
Japan
State/province [36] 0 0
Kanagawa
Country [37] 0 0
Japan
State/province [37] 0 0
Miyagi
Country [38] 0 0
Japan
State/province [38] 0 0
Okayama
Country [39] 0 0
Japan
State/province [39] 0 0
Osaka
Country [40] 0 0
Japan
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Tokyo
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Korea, Republic of
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Seocho Gu
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Korea, Republic of
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Seoul
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Malaysia
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Selangor Darul Ehsan
Country [44] 0 0
Malaysia
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Kuala Lumpur
Country [45] 0 0
Netherlands
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Groningen
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Norway
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Bergen
Country [47] 0 0
Norway
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Loerenskog
Country [48] 0 0
Norway
State/province [48] 0 0
Oslo
Country [49] 0 0
Singapore
State/province [49] 0 0
Singapore
Country [50] 0 0
Spain
State/province [50] 0 0
Catalunya
Country [51] 0 0
Spain
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Madrid
Country [52] 0 0
Sweden
State/province [52] 0 0
Lund
Country [53] 0 0
Sweden
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Stockholm
Country [54] 0 0
Taiwan
State/province [54] 0 0
New Taipei City
Country [55] 0 0
Taiwan
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Taichung
Country [56] 0 0
Taiwan
State/province [56] 0 0
Taipei
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taoyuan
Country [58] 0 0
Thailand
State/province [58] 0 0
Bangkok
Country [59] 0 0
Turkey
State/province [59] 0 0
TUR
Country [60] 0 0
Turkey
State/province [60] 0 0
Ankara
Country [61] 0 0
Turkey
State/province [61] 0 0
Kocaeli
Country [62] 0 0
Turkey
State/province [62] 0 0
Talas / Kayseri
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Cambrigdeshire
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Manchester
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leicester
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Newcastle Upon Tyne

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

Ethics approval
Ethics application status

Summary
Brief summary
Efficacy and safety of LNP023 in IgAN patients
Trial website
https://clinicaltrials.gov/show/NCT03373461
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03373461