E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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 |
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E.2.2 | Secondary objectives of the trial |
• 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cohort A
•Patients (females and males 18 years or older in age) must have C3G as confirmed by renal biopsy within twelve months prior to enrollment (confirmation by the Investigator is required).
•C3G patients with reduced C3 at screening (defined as less than 0.90 x lower limit of the lab normal ranges) are eligible for this study.
•Estimated GFR (using the CKD-EPI formula) ≥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 sampled from first morning void (or ≥ 1 g/24h total urinary protein excretion from a 24h urinary collection during runin) at run-in (Visit 20) or at baseline (Visit 30).
•Any antiproteinuric medication (e.g., angiotensin converting enzyme inhibitors, angiotensin II receptor blockers) must be at a stable dose for at least 30 days prior to treatment start.
•Previous vaccination against Neisseria meningitidis is required at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should not have taken place more than 3 years prior to LNP treatment). If
LNP023 treatment has to start earlier than 4 weeks post last vaccination dose, prophylactic antibiotic treatment must be initiated.
•Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should not have taken place more than 3 years prior to LNP
treatment). If LNP023 treatment has to start earlier than 4 weeks post last vaccination dose, prophylactic antibiotic treatment must be initiated.
Cohort B
•Patients (females and males 18 years or older in age) must have C3G
recurrence after transplantation as confirmed by renal biopsy after
transplantation within twelve months prior to enrollment (confirmation
by the Investigator is required).
•Estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2
•Normal or elevated urinary protein excretion at screening or at baseline (Visit 30).
•Previous vaccination against Neisseria meningitidis is required at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should not have taken place more than 3 years prior to LNP treatment). If LNP023 treatment has to start earlier than 4 weeks post last vaccination dose, prophylactic antibiotic treatment must be initiated.
•Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should not have taken place more than 3 years prior to LNP treatment). If LNP023 treatment has to start earlier than 4 weeks post last vaccination dose, prophylactic antibiotic treatment must be initiated.
•If applicable, induction treatment after allotransplantation needs to be completed >30 days before inclusion. Any commercially available
induction agent is permitted.
•Patients need to be on a stable dose of immunosuppressive regimen
prior to Day 1. Any commercially available treatments are allowed for
this purpose.(if not prohibited as per protocol)
•Transplantation of a kidney allograft >30 days before screening
•No histologic signs of allorejection |
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E.4 | Principal exclusion criteria |
Cohort A
•Known family history or known presence of long QT syndrome or Torsades de Pointes.
•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
•Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
•Plasma donation (>200 mL) within 30 days prior to first dosing.
•Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae.
•Use of other investigational drugs at the time of enrollment, or within 5 half-lives, or within 30 days of screening, whichever is longer; or longer if required by local regulations.
Cohort B
•Known family history or known presence of long QT syndrome or Torsades de Pointes.
•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.
•Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
•Plasma donation (>200 mL) within 30 days prior to first dosing.
•Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae.
•Use of other investigational drugs at the time of enrollment, or within 5 half-lives, or within 30 days of screening, whichever is longer; or longer if required by local regulations.
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohort A: Change from baseline in UPCR
Cohort B: Change from baseline in C3 Deposit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
PD variables
Pharmacokinetics variables
Biomarker C3
Biomarker Bb |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |