C3 glomerulopathy
Conditions
Interventions
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet established
CAS Number: 1646321-63-2
Other descriptive name: LNP023
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 with 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 . Cohort A: - Estimated GFR (using the CKD-EPI formula) or measured GFR =30mL/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. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Cohort A: To evaluate the efficacy of LNP023 in reducing proteinuria at Week 12 • Cohort B: To assess histopathological changes in kidney biopsies at Week 12;Primary end point(s): Cohort A: Change from baseline in UPCR Cohort B: Change from baseline in C3 Deposit;Timepoint(s) of evaluation of this end point: Week 12;Secondary Objective: • All Cohorts: To assess the relationship between LNP023 dose and proteinuria • All Cohorts: To assess the effect of LNP023 on renal function • All Cohorts: To assess the effect of LNP023 on alternative complement pathway hyperactivity • All Cohorts: To assess the safety and tolerability of LNP023 • All Cohorts: To assess the plasma and urine pharmacokinetics of LNP023 in patients with C3G • Cohort B: To evaluate the efficacy of LNP023 in reducing proteinuria at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PD variables Pharmacokinetics variables Biomarker C3 Biomarker Bb;Timepoint(s) of evaluation of this end point: PD variables Week 12 Pharmacokinetics variables Week 1, 2, 3, 4, 13, 14 Biomarker C3 Week 1,2, 3, 4, and 12 Biomarker Bb Week 1, 2, 3, 4 and 12 | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica, S.A.
Outcome results
None listed