Glomerulonephritis Clinical Trial
Official title:
An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
Verified date | January 2024 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 27 |
Est. completion date | April 23, 2021 |
Est. primary completion date | April 23, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
France | Novartis Investigative Site | Montpellier | |
France | Novartis Investigative Site | Paris | |
Germany | Novartis Investigative Site | Essen | |
Italy | Novartis Investigative Site | Ranica | BG |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Madrid | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | Newcastle Upon Tyne | |
United States | Novartis Investigative Site | Iowa City | Iowa |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, France, Germany, Italy, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR) | Ratio to baseline UPCR derived from 24 hour urine collection | Week 12: Day 84 | |
Secondary | Change From Baseline in Urine Protein (UP) Excretion | Ratio to baseline UP excretion derived from 24 hour urine collection | Week 12: Day 84 | |
Secondary | 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 | |
Secondary | Change From Baseline Change in Urinary Albumin (UA) Excretion | Ratio to baseline UA excretion derived from 24 hour urine collection | Week 12: Day 84 | |
Secondary | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Effect of LNP023 on estimated glomerular filtration rate (eGFR) | Day 84 | |
Secondary | Change From Baseline in Serum Creatinine | The effect of LNP023 on renal function - serum creatinine | Week 12: Day 84 | |
Secondary | Change From Baseline in Creatinine Clearance | The effect of LNP023 on renal function - creatinine clearance | Week 12: Day 84 | |
Secondary | Number of Patients With Hematuria | The effect of LNP023 on renal function - hematuria | Week 12: Day 84 | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | 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) | |
Secondary | 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) | |
Secondary | 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) | |
Secondary | 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) | |
Secondary | 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) | |
Secondary | 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 | |
Secondary | 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 |
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