Study on efficacy and safety of LNP023 in C3 glomerulopathy patients transplanted and not transplanted
- Conditions
- Therapeutic area: Diseases [C] - Immune System Diseases [C20]C3 glomerulopathy
- Registration Number
- EUCTR2017-000889-29-ES
- Lead Sponsor
- ovartis Farmacéutica, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 27
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • Cohort A: To evaluate the efficacy of LNP023 in reducing proteinuria at Week 12<br>• Cohort B: To assess histopathological changes in kidney biopsies at Week 12;Primary end point(s): Cohort A: Change from baseline in UPCR<br>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<br>proteinuria<br>• All Cohorts: To assess the effect of LNP023 on renal function<br>• All Cohorts: To assess the effect of LNP023 on alternative<br>complement pathway hyperactivity<br>• All Cohorts: To assess the safety and tolerability of LNP023<br>• All Cohorts: To assess the plasma and urine pharmacokinetics of<br>LNP023 in patients with C3G<br>• Cohort B: To evaluate the efficacy of LNP023 in reducing proteinuria<br>at Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): PD variables<br>Pharmacokinetics variables<br>Biomarker C3<br>Biomarker Bb;Timepoint(s) of evaluation of this end point: PD variables Week 12<br>Pharmacokinetics variables Week 1, 2, 3, 4, 13, 14<br>Biomarker C3 Week 1,2, 3, 4, and 12<br>Biomarker Bb Week 1, 2, 3, 4 and 12