Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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ClinicalTrials.gov |
Last refreshed on:
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6 February 2023 |
Main ID: |
NCT03373461 |
Date of registration:
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30/11/2017 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation
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Scientific title:
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An Adaptive Seamless Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients |
Date of first enrolment:
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February 7, 2018 |
Target sample size:
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112 |
Recruitment status: |
Completed |
URL:
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https://clinicaltrials.gov/show/NCT03373461 |
Study type:
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Interventional |
Study design:
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Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
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Phase:
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Phase 2
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Countries of recruitment
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Argentina
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Australia
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Belgium
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Brazil
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China
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Colombia
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Czechia
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Denmark
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Finland
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France
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Germany
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Hong Kong
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Hungary
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India
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Israel
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Italy
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Japan
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Korea, Republic of
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Malaysia
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Netherlands
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Norway
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Singapore
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Spain
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Sweden
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Taiwan
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Thailand
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Turkey
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United Kingdom
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United States
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Key inclusion & exclusion criteria
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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
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
Age minimum:
18 Years
Age maximum:
N/A
Gender:
All
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Health Condition(s) or Problem(s) studied
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IgA Nephropathy
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Intervention(s)
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Other: Placebo
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Drug: LNP023
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Primary Outcome(s)
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MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90
[Time Frame: Baseline and Day 90]
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Secondary Outcome(s)
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Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180
[Time Frame: Baseline and Day 180]
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Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90
[Time Frame: Baseline and Day 90]
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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
[Time Frame: Baseline, Days 30, 90 and 180]
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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
[Time Frame: Baseline and Day 180]
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Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90
[Time Frame: Baseline and Day 90]
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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
[Time Frame: Baseline and Day 90]
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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
[Time Frame: Baseline and Day 90]
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Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90
[Time Frame: Baseline and Day 90]
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Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30
[Time Frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)]
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Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90
[Time Frame: Baseline up to Month 3]
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Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30
[Time Frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)]
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Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90
[Time Frame: Baseline and Day 90]
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Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90
[Time Frame: Baseline and Day 90]
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Percent of LNP023 Excreted Into Urine at Day 30
[Time Frame: Baseline and Day 30]
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Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30
[Time Frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)]
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Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30
[Time Frame: Baseline and Day 30]
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Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180
[Time Frame: Baseline and Day 180]
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Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30
[Time Frame: Baseline and Day 30]
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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
[Time Frame: Baseline, Days 8, 15, 30, 60, 90]
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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
[Time Frame: Baseline and Day 180]
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Secondary ID(s)
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CLNP023X2203
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2017-000891-27
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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