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

An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy

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).

Study Overview

• Status: Completed
• Conditions: Glomerulonephritis
• Intervention / Treatment: Drug: LNP023

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
• Italy
  • BG
    • Ranica, BG, Italy, 24020
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0NN
    • Novartis Investigative Site
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Novartis Investigative Site
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 immunosuppressive 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 12
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)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)	Ratio to baseline UPCR derived from 24 hour urine collection	Week 12: Day 84
Change From Baseline in Urine Protein (UP) Excretion	Ratio to baseline UP excretion derived from 24 hour urine collection	Week 12: Day 84
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion	Ratio to baseline UACR excretion derived from 24 hour urine collection	Week 12: Day 84
Change From Baseline Change in Urinary Albumin (UA) Excretion	Ratio to baseline UA excretion derived from 24 hour urine collection	Week 12: Day 84
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	Effect of LNP023 on estimated glomerular filtration rate (eGFR)	Day 84
Change From Baseline in Serum Creatinine	The effect of LNP023 on renal function - serum creatinine	Week 12: Day 84
Change From Baseline in Creatinine Clearance	The effect of LNP023 on renal function - creatinine clearance	Week 12: Day 84
Number of Patients With Hematuria	The effect of LNP023 on renal function - hematuria	Week 12: Day 84
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	Week 9: Day 64
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	Week 9: Day 64
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)	The area under the plasma concentration-time curve calculated from time zero to the last quantifiable concentration point (hr*ng/mL)	Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)	The area under the plasma concentration-time curve calculated to the end of the dosing interval (hr*ng/mL)	Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Maximum Concentration After Drug Administration (Cmax)	The observed maximum plasma concentration (ng/mL)	Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Minimum Concentration After Drug Administration (Ctrough)	The concentration that is just prior to the beginning of, or at the end, of a dosing interval (ng/mL)	Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Time to Reach the Maximum Plasma Concentration (Tmax)	The time to reach peak or maximum concentration (hr)	Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Summary of Change From Baseline Complement C3 Biomarker in Serum	To assess the effect of LNP023 on alternative complement pathway hyperactivity.	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Ratio to Baseline Summary of Plasma Bb	To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Link to plain language trial summary

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2019
• Primary Completion (Actual): April 23, 2021
• Study Completion (Actual): April 23, 2021

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis
• Other Study ID Numbers: CLNP023X2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No