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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03373461
Ethics application status
Date submitted
30/11/2017
Date registered
14/12/2017

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
Other interventions - Placebo

Placebo comparator: Placebo - Placebo identical to LNP023 twice a day

Experimental: LNP023 10 mg BID - 10 mg taken twice a day.

Experimental: LNP023 50 mg BID - 50 mg taken twice a day.

Experimental: LNP023 100 mg BID - Part 2 - 100 mg taken twice a day.

Experimental: LNP023 200 mg BID - 200 mg taken twice a day.


Treatment: Drugs: LNP023
LNP023 5, 25, 100 mg capsles

Other interventions: Placebo
Matching placebo to LNP023
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90
Timepoint [1] 0 0
Baseline and Day 90
Secondary outcome [1] 0 0
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90
Timepoint [1] 0 0
Baseline and Day 90
Secondary outcome [2] 0 0
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90
Timepoint [2] 0 0
Baseline and Day 90
Secondary outcome [3] 0 0
Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90
Timepoint [3] 0 0
Baseline and Day 90
Secondary outcome [4] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90
Timepoint [4] 0 0
Baseline and Day 90
Secondary outcome [5] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90
Timepoint [5] 0 0
Baseline and Day 90
Secondary outcome [6] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90
Timepoint [6] 0 0
Baseline and Day 90
Secondary outcome [7] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90
Timepoint [7] 0 0
Baseline and Day 90
Secondary outcome [8] 0 0
Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30
Timepoint [8] 0 0
Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Secondary outcome [9] 0 0
Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30
Timepoint [9] 0 0
Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Secondary outcome [10] 0 0
Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30
Timepoint [10] 0 0
Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Secondary outcome [11] 0 0
Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30
Timepoint [11] 0 0
Baseline and Day 30
Secondary outcome [12] 0 0
Percent of LNP023 Excreted Into Urine at Day 30
Timepoint [12] 0 0
Baseline and Day 30
Secondary outcome [13] 0 0
Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30
Timepoint [13] 0 0
Baseline and Day 30
Secondary outcome [14] 0 0
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90
Timepoint [14] 0 0
Baseline, Days 8, 15, 30, 60, 90
Secondary outcome [15] 0 0
Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90
Timepoint [15] 0 0
Baseline up to Month 3
Secondary outcome [16] 0 0
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180
Timepoint [16] 0 0
Baseline and Day 180
Secondary outcome [17] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180
Timepoint [17] 0 0
Baseline and Day 180
Secondary outcome [18] 0 0
Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180
Timepoint [18] 0 0
Baseline and Day 180
Secondary outcome [19] 0 0
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180
Timepoint [19] 0 0
Baseline, Days 30, 90 and 180
Secondary outcome [20] 0 0
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180
Timepoint [20] 0 0
Baseline and Day 180

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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/06/2021
Sample size
Target
Accrual to date
Final
112
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
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Belgium
State/province [2] 0 0
Antwerpen
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Roeselare
Country [5] 0 0
Brazil
State/province [5] 0 0
PR
Country [6] 0 0
Brazil
State/province [6] 0 0
RS
Country [7] 0 0
China
State/province [7] 0 0
Guangdong
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
China
State/province [9] 0 0
Guang Zhou
Country [10] 0 0
China
State/province [10] 0 0
Shanghai
Country [11] 0 0
Colombia
State/province [11] 0 0
Barranquilla
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha
Country [13] 0 0
Denmark
State/province [13] 0 0
Aalborg
Country [14] 0 0
Denmark
State/province [14] 0 0
Arhus N
Country [15] 0 0
Finland
State/province [15] 0 0
HUS
Country [16] 0 0
France
State/province [16] 0 0
Montpellier
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Hong Kong
State/province [19] 0 0
Hong Kong SAR
Country [20] 0 0
India
State/province [20] 0 0
Delhi
Country [21] 0 0
India
State/province [21] 0 0
New Delhi
Country [22] 0 0
Israel
State/province [22] 0 0
Ashkelon
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Petach Tikva
Country [25] 0 0
Japan
State/province [25] 0 0
Aichi
Country [26] 0 0
Japan
State/province [26] 0 0
Hokkaido
Country [27] 0 0
Japan
State/province [27] 0 0
Miyagi
Country [28] 0 0
Japan
State/province [28] 0 0
Okayama
Country [29] 0 0
Japan
State/province [29] 0 0
Osaka
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Malaysia
State/province [31] 0 0
Kuala Lumpur
Country [32] 0 0
Netherlands
State/province [32] 0 0
Groningen
Country [33] 0 0
Norway
State/province [33] 0 0
Bergen
Country [34] 0 0
Norway
State/province [34] 0 0
Loerenskog
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore
Country [37] 0 0
Sweden
State/province [37] 0 0
Lund
Country [38] 0 0
Sweden
State/province [38] 0 0
Stockholm
Country [39] 0 0
Taiwan
State/province [39] 0 0
New Taipei City
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taichung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
Thailand
State/province [42] 0 0
Bangkok
Country [43] 0 0
Turkey
State/province [43] 0 0
TUR
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Kocaeli
Country [46] 0 0
Turkey
State/province [46] 0 0
Talas / Kayseri
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Cambrigdeshire
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Manchester
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Leicester
Country [50] 0 0
United Kingdom
State/province [50] 0 0
London
Country [51] 0 0
United Kingdom
State/province [51] 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
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03373461