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Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted

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ClinicalTrials.gov Identifier: NCT03832114
Recruitment Status : Completed
First Posted : February 6, 2019
Results First Posted : July 8, 2022
Last Update Posted : August 10, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Glomerulonephritis Drug: LNP023 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention 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
Primary Purpose: Treatment
Official Title: An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
Actual Study Start Date : February 20, 2019
Actual Primary Completion Date : April 23, 2021
Actual Study Completion Date : April 23, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A - no kidney transplant
C3G patients who have not received a kidney transplant and have reduced C3 blood levels.
Drug: LNP023
Increasing doses of LNP023 up to 200 mg.

Experimental: Cohort B - kidney transplant
C3G patients who have received a kidney transplant and have C3G recurrence.
Drug: LNP023
Increasing doses of LNP023 up to 200 mg.




Primary Outcome Measures :
  1. Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) [ Time Frame: Week 12 ]
    Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection

  2. Cohort B: Change From Baseline in C3 Deposit [ Time Frame: Week 12 ]
    Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)


Secondary Outcome Measures :
  1. Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR) [ Time Frame: Week 12: Day 84 ]
    Ratio to baseline UPCR derived from 24 hour urine collection

  2. Change From Baseline in Urine Protein (UP) Excretion [ Time Frame: Week 12: Day 84 ]
    Ratio to baseline UP excretion derived from 24 hour urine collection

  3. Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion [ Time Frame: Week 12: Day 84 ]
    Ratio to baseline UACR excretion derived from 24 hour urine collection

  4. Change From Baseline Change in Urinary Albumin (UA) Excretion [ Time Frame: Week 12: Day 84 ]
    Ratio to baseline UA excretion derived from 24 hour urine collection

  5. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Day 84 ]
    Effect of LNP023 on estimated glomerular filtration rate (eGFR)

  6. Change From Baseline in Serum Creatinine [ Time Frame: Week 12: Day 84 ]
    The effect of LNP023 on renal function - serum creatinine

  7. Change From Baseline in Creatinine Clearance [ Time Frame: Week 12: Day 84 ]
    The effect of LNP023 on renal function - creatinine clearance

  8. Number of Patients With Hematuria [ Time Frame: Week 12: Day 84 ]
    The effect of LNP023 on renal function - hematuria

  9. Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void [ Time Frame: Week 9: Day 64 ]
    Ratio to baseline of UPCR reduction derived from total cumulative urinary excretion first morning void

  10. Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void [ Time Frame: Week 9: Day 64 ]
    UACR reduction derived from total cumulative urinary excretion first morning void

  11. Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC) [ Time Frame: Weeks 1, 2, 3, 4 ]
    Plasma: Non-compartmental parameter analysis related to total drug for the area under the plasma-concentration-time curve calculated from time

  12. Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC) [ Time Frame: Weeks 1, 2, 3, 4 ]
    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)

  13. Observed Maximum Concentration After Drug Administration (Cmax) [ Time Frame: Weeks 1, 2, 3, 4 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Cmax after the first dose.

  14. Observed Mimum Concentration After Drug Administration (Ctrough) [ Time Frame: Weeks 1, 2, 3, 4 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Ctrough (Cmin) after the first dose.

  15. Time to Reach the Maximum Plasma Concentration (Tmax) [ Time Frame: Weeks 1, 2, 3, 4 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Tmax after the first dose.

  16. Summary of Change From Baseline Complement C3 Biomarker in Serum [ Time Frame: Weeks 1, 2, 3, 4, 12 ]
    To assess the effect of LNP023 on alternative complement pathway hyperactivity

  17. Ratio to Baseline Summary of Plasma Bb in Blood and Urine [ Time Frame: Week 1, 2, 3, 4 and 12 ]
    To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb in blood and urine



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03832114


Locations
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United States, Iowa
Novartis Investigative Site
Iowa City, Iowa, United States, 52242
France
Novartis Investigative Site
Montpellier, France, 34295
Novartis Investigative Site
Paris, France, 75015
Germany
Novartis Investigative Site
Essen, Germany, 45147
Italy
Novartis Investigative Site
Ranica, BG, Italy, 24020
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Madrid, Spain, 28041
United Kingdom
Novartis Investigative Site
London, United Kingdom, W12 0NN
Novartis Investigative Site
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] February 7, 2020
Statistical Analysis Plan  [PDF] December 2, 2021

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03832114    
Other Study ID Numbers: CLNP023X2202
First Posted: February 6, 2019    Key Record Dates
Results First Posted: July 8, 2022
Last Update Posted: August 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases