Study on efficacy and safety of LNP023 in C3 glomerulopathy patients transplanted and not transplanted

Phase 1

Conditions: C3 glomerulopathy
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2017-000889-29-GB

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 27

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
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

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.

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;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;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 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

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