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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 : Recruiting
First Posted : February 6, 2019
Last Update Posted : August 29, 2019
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)
Estimated 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
Estimated Primary Completion Date : August 18, 2020
Estimated Study Completion Date : September 16, 2020

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 UPCR and Urine Albumine to Creatinine concentration Ratio (UACR) [ Time Frame: Baseline, Week 12 ]
    Ratio to baseline of UPCR and UACR derived from 24h urine collection

  2. Change from baseline in Urine Protein (UP) and Urine Albumin (UA) concentration [ Time Frame: Baseline, Week 12 ]
    Change and evolution of UA and UP

  3. The effect of LNP023 on renal function - serum creatinine [ Time Frame: Baseline, Week 12 ]
    Change and evolution of serum creatinine and creatinine clearance

  4. The effect of LNP023 on renal function - estimated glomerular filtration rate [ Time Frame: Baseline, Week 12 ]
    Change and evolution of eGFR

  5. The effect of LNP023 on renal function - hematuria [ Time Frame: Baseline, Week 12 ]
    Change and evolution of hematuria

  6. Pharmacokinetics of LNP023 Area under the Plasma-concentration-time curve (AUC) [ Time Frame: Week 1, 2, 3, 4, 13, 14 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to AUClast, AUCtau after the first dose.

  7. Observed maximum concentration after drug administration [ Time Frame: Week 1, 2, 3, 4, 13, 14 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Cmax after the first dose.

  8. Observed mimum concentration after drug administration [ Time Frame: Week 1, 2, 3, 4, 13, 14 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Ctrough (Cmin) after the first dose.

  9. Time to reach the maximum plasma concentration (Tmax) [ Time Frame: Week 1, 2, 3, 4, 13, 14 ]
    Plasma: Non-compartmental parameter analysis related to total drug, including but not limited to Tmax after the first dose.

  10. Pharmacokinetics of LNP023 in urine [ Time Frame: Week 1, 2, 3, 4, 13, 14 ]
    Non-compartmental parameters, including but not limited to total cumulative urinary excretion and renal plasma clearance.

  11. Biomarker C3 [ Time Frame: Week 1,2, 3, 4, and 12 ]
    To assess the effect of LNP023 on alternative complement pathway hyperactivity

  12. Biomarker Bb [ Time Frame: Week 1, 2, 3, 4 and 12 ]
    To assess the relationship between LNP023 dose and pharmacodynamic biomarker Bb



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (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 (ELISA and Western blot) 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


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 guido.junge@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Iowa
Novartis Investigative Site Recruiting
Iowa City, Iowa, United States, 52242
France
Novartis Investigative Site Recruiting
Montpellier, France, 34295
Novartis Investigative Site Recruiting
Nantes, France, 44093
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Italy
Novartis Investigative Site Recruiting
Ranica, BG, Italy, 24020
Spain
Novartis Investigative Site Recruiting
L Hospitalet De Llobregat, Barcelona, Spain, 08907
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
United Kingdom
Novartis Investigative Site Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03832114     History of Changes
Other Study ID Numbers: CLNP023X2202
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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