Clinical trial NCT03832114: Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
Official title: An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glomerulonephritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-02-06
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 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).
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)
timeFrame: Week 12
measure: Cohort B: Change From Baseline in C3 Deposit
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)
timeFrame: Week 12: Day 84
measure: Change From Baseline in Urine Protein (UP) Excretion
timeFrame: Week 12: Day 84
measure: Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion
timeFrame: Week 12: Day 84
measure: Change From Baseline Change in Urinary Albumin (UA) Excretion
timeFrame: Week 12: Day 84
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Day 84
measure: Change From Baseline in Serum Creatinine
timeFrame: Week 12: Day 84
measure: Change From Baseline in Creatinine Clearance
timeFrame: Week 12: Day 84
measure: Number of Patients With Hematuria
timeFrame: Week 12: Day 84
measure: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void
timeFrame: Week 9: Day 64
measure: Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void
timeFrame: Week 9: Day 64
measure: Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)
timeFrame: 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)
measure: Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)
timeFrame: 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)
measure: Observed Maximum Concentration After Drug Administration (Cmax)
timeFrame: 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)
measure: Observed Minimum Concentration After Drug Administration (Ctrough)
timeFrame: 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)
measure: Time to Reach the Maximum Plasma Concentration (Tmax)
timeFrame: 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)
measure: Summary of Change From Baseline Complement C3 Biomarker in Serum
timeFrame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
measure: Ratio to Baseline Summary of Plasma Bb
timeFrame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Novartis Investigative Site
state: Iowa
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Ranica
country: Italy
facility: Novartis Investigative Site
state: BG
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: