Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
Primary Purpose
Glomerulonephritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LNP023
Sponsored by
About this trial
This is an interventional treatment trial for Glomerulonephritis
Eligibility Criteria
Inclusion Criteria for Cohort A and B:
- Written informed consent must be obtained before any assessment is performed
- Male and female patients between the ages of 18 to 65 (inclusive) at screening
- C3G patients wit proteinuria
- Able to communicate well with the investigator, to understand and comply with the requirements of the study
- At screening and baseline visits, patients must weigh at least 35 kg
- Supine vital signs should be within the following ranges :
oral body temperature between 35.0-37.5 °C systolic blood pressure, 80-170 mm Hg diastolic blood pressure, 50-105 mm Hg pulse rate, 45 - 100 bpm
.
Inclusion Criteria for Cohort A:
- Estimated GFR (using the CKD-EPI formula) or measured GFR ≥30 mL/min per 1.73 m2 for patients on a maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
- UPCR ≥ 100 mg/mmol (equivalent to ≥ 1 g/24h total urinary protein excretion)
- Prior to entry, all patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB for at least 30 days.
Inclusion Criteria for Cohort B:
- No histological/laboratory/clinical signs of allorejection
- If applicable, induction treatment after allotransplantation needs to be completed >30 days before inclusion.
- Transplantation of a kidney allograft >90 days before inclusion
- Patients need to be on a stable dose of immunsuppressive regimen prior to inclusion. Any approved treatments are allowed for this purpose.
Exclusion Criteria for Cohort A and B:
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations
- A history of clinically significant ECG abnormalities,
- Known family history or known presence of long QT syndrome or Torsades de Pointes
- Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
- 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.
- 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.
- History of immunodeficiency diseases, or a positive HIV test result.
- Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
- Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A - no kidney transplant
Cohort B - kidney transplant
Arm Description
C3G patients who have not received a kidney transplant and have reduced C3 blood levels.
C3G patients who have received a kidney transplant and have C3G recurrence.
Outcomes
Primary Outcome Measures
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)
Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection
Cohort B: Change From Baseline in C3 Deposit
Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)
Secondary Outcome Measures
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)
Ratio to baseline UPCR derived from 24 hour urine collection
Change From Baseline in Urine Protein (UP) Excretion
Ratio to baseline UP excretion derived from 24 hour urine collection
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion
Ratio to baseline UACR excretion derived from 24 hour urine collection
Change From Baseline Change in Urinary Albumin (UA) Excretion
Ratio to baseline UA excretion derived from 24 hour urine collection
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Effect of LNP023 on estimated glomerular filtration rate (eGFR)
Change From Baseline in Serum Creatinine
The effect of LNP023 on renal function - serum creatinine
Change From Baseline in Creatinine Clearance
The effect of LNP023 on renal function - creatinine clearance
Number of Patients With Hematuria
The effect of LNP023 on renal function - hematuria
Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void
Ratio to baseline of UPCR reduction derived from total cumulative urinary excretion first morning void
Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void
UACR reduction derived from total cumulative urinary excretion first morning void
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)
Plasma: Non-compartmental parameter analysis related to total drug for the area under the plasma-concentration-time curve calculated from time
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)
Plasma: Non-compartmental parameter analysis related to total drug for the area under the plasma-concentration-time curve calculated to the end of the dosing interval (ngxh/mL)
Observed Maximum Concentration After Drug Administration (Cmax)
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Cmax after the first dose.
Observed Mimum Concentration After Drug Administration (Ctrough)
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Ctrough (Cmin) after the first dose.
Time to Reach the Maximum Plasma Concentration (Tmax)
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Tmax after the first dose.
Summary of Change From Baseline Complement C3 Biomarker in Serum
To assess the effect of LNP023 on alternative complement pathway hyperactivity
Ratio to Baseline Summary of Plasma Bb in Blood and Urine
To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb in blood and urine
Full Information
NCT ID
NCT03832114
First Posted
January 28, 2019
Last Updated
August 8, 2022
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03832114
Brief Title
Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
Official Title
An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
February 20, 2019 (Actual)
Primary Completion Date
April 23, 2021 (Actual)
Study Completion Date
April 23, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glomerulonephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
Masking
None (Open Label)
Masking Description
Open label study
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A - no kidney transplant
Arm Type
Experimental
Arm Description
C3G patients who have not received a kidney transplant and have reduced C3 blood levels.
Arm Title
Cohort B - kidney transplant
Arm Type
Experimental
Arm Description
C3G patients who have received a kidney transplant and have C3G recurrence.
Intervention Type
Drug
Intervention Name(s)
LNP023
Intervention Description
Increasing doses of LNP023 up to 200 mg.
Primary Outcome Measure Information:
Title
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)
Description
Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection
Time Frame
Week 12
Title
Cohort B: Change From Baseline in C3 Deposit
Description
Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)
Description
Ratio to baseline UPCR derived from 24 hour urine collection
Time Frame
Week 12: Day 84
Title
Change From Baseline in Urine Protein (UP) Excretion
Description
Ratio to baseline UP excretion derived from 24 hour urine collection
Time Frame
Week 12: Day 84
Title
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion
Description
Ratio to baseline UACR excretion derived from 24 hour urine collection
Time Frame
Week 12: Day 84
Title
Change From Baseline Change in Urinary Albumin (UA) Excretion
Description
Ratio to baseline UA excretion derived from 24 hour urine collection
Time Frame
Week 12: Day 84
Title
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Description
Effect of LNP023 on estimated glomerular filtration rate (eGFR)
Time Frame
Day 84
Title
Change From Baseline in Serum Creatinine
Description
The effect of LNP023 on renal function - serum creatinine
Time Frame
Week 12: Day 84
Title
Change From Baseline in Creatinine Clearance
Description
The effect of LNP023 on renal function - creatinine clearance
Time Frame
Week 12: Day 84
Title
Number of Patients With Hematuria
Description
The effect of LNP023 on renal function - hematuria
Time Frame
Week 12: Day 84
Title
Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void
Description
Ratio to baseline of UPCR reduction derived from total cumulative urinary excretion first morning void
Time Frame
Week 9: Day 64
Title
Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void
Description
UACR reduction derived from total cumulative urinary excretion first morning void
Time Frame
Week 9: Day 64
Title
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)
Description
Plasma: Non-compartmental parameter analysis related to total drug for the area under the plasma-concentration-time curve calculated from time
Time Frame
Weeks 1, 2, 3, 4
Title
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)
Description
Plasma: Non-compartmental parameter analysis related to total drug for the area under the plasma-concentration-time curve calculated to the end of the dosing interval (ngxh/mL)
Time Frame
Weeks 1, 2, 3, 4
Title
Observed Maximum Concentration After Drug Administration (Cmax)
Description
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Cmax after the first dose.
Time Frame
Weeks 1, 2, 3, 4
Title
Observed Mimum Concentration After Drug Administration (Ctrough)
Description
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Ctrough (Cmin) after the first dose.
Time Frame
Weeks 1, 2, 3, 4
Title
Time to Reach the Maximum Plasma Concentration (Tmax)
Description
Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Tmax after the first dose.
Time Frame
Weeks 1, 2, 3, 4
Title
Summary of Change From Baseline Complement C3 Biomarker in Serum
Description
To assess the effect of LNP023 on alternative complement pathway hyperactivity
Time Frame
Weeks 1, 2, 3, 4, 12
Title
Ratio to Baseline Summary of Plasma Bb in Blood and Urine
Description
To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb in blood and urine
Time Frame
Week 1, 2, 3, 4 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for Cohort A and B:
Written informed consent must be obtained before any assessment is performed
Male and female patients between the ages of 18 to 65 (inclusive) at screening
C3G patients wit proteinuria
Able to communicate well with the investigator, to understand and comply with the requirements of the study
At screening and baseline visits, patients must weigh at least 35 kg
Supine vital signs should be within the following ranges :
oral body temperature between 35.0-37.5 °C systolic blood pressure, 80-170 mm Hg diastolic blood pressure, 50-105 mm Hg pulse rate, 45 - 100 bpm
.
Inclusion Criteria for Cohort A:
Estimated GFR (using the CKD-EPI formula) or measured GFR ≥30 mL/min per 1.73 m2 for patients on a maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
UPCR ≥ 100 mg/mmol (equivalent to ≥ 1 g/24h total urinary protein excretion)
Prior to entry, all patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB for at least 30 days.
Inclusion Criteria for Cohort B:
No histological/laboratory/clinical signs of allorejection
If applicable, induction treatment after allotransplantation needs to be completed >30 days before inclusion.
Transplantation of a kidney allograft >90 days before inclusion
Patients need to be on a stable dose of immunsuppressive regimen prior to inclusion. Any approved treatments are allowed for this purpose.
Exclusion Criteria for Cohort A and B:
Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations
A history of clinically significant ECG abnormalities,
Known family history or known presence of long QT syndrome or Torsades de Pointes
Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
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.
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.
History of immunodeficiency diseases, or a positive HIV test result.
Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae
Facility Information:
Facility Name
Novartis Investigative Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Novartis Investigative Site
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Ranica
State/Province
BG
ZIP/Postal Code
24020
Country
Italy
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1070
Description
link to plain language trial summary
Learn more about this trial
Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
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