Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted

Phase 2

Completed

• Conditions: Glomerulonephritis
• Interventions: Drug: LNP023

• Registration Number: NCT03832114
• Lead Sponsor: Novartis Pharmaceuticals

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-28
• Study First Submitted QC: 2019-02-04
• Study First Posted: 2019-02-06
• Study Start: 2019-02-20
• Primary Completion: 2021-04-23
• Study Completion: 2021-04-23
• Results First Submitted: 2022-04-22
• Results First Submitted QC: 2022-06-13
• Results First Posted: 2022-07-08
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Last Update Posted: 2024-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort A - no kidney transplant	LNP023	C3G patients who have not received a kidney transplant and have reduced C3 blood levels.
Cohort B - kidney transplant	LNP023	C3G patients who have received a kidney transplant and have C3G recurrence.

Primary Outcome Measures

Name	Time	Method
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)	Week 12	Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection
Cohort B: Change From Baseline in C3 Deposit	Week 12	Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion	Week 12: Day 84	Ratio to baseline UACR excretion derived from 24 hour urine collection
Time to Reach the Maximum Plasma Concentration (Tmax)	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)	The time to reach peak or maximum concentration (hr)
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)	Week 12: Day 84	Ratio to baseline UPCR derived from 24 hour urine collection
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	Day 84	Effect of LNP023 on estimated glomerular filtration rate (eGFR)
Change From Baseline in Serum Creatinine	Week 12: Day 84	The effect of LNP023 on renal function - serum creatinine
Number of Patients With Hematuria	Week 12: Day 84	The effect of LNP023 on renal function - hematuria
Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void	Week 9: Day 64	Ratio to baseline of UPCR reduction derived from total cumulative urinary excretion first morning void
Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void	Week 9: Day 64	UACR reduction derived from total cumulative urinary excretion first morning void
Change From Baseline in Urine Protein (UP) Excretion	Week 12: Day 84	Ratio to baseline UP excretion derived from 24 hour urine collection
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)	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)	The area under the plasma concentration-time curve calculated from time zero to the last quantifiable concentration point (hr\*ng/mL)
Observed Maximum Concentration After Drug Administration (Cmax)	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)	The observed maximum plasma concentration (ng/mL)
Change From Baseline Change in Urinary Albumin (UA) Excretion	Week 12: Day 84	Ratio to baseline UA excretion derived from 24 hour urine collection
Change From Baseline in Creatinine Clearance	Week 12: Day 84	The effect of LNP023 on renal function - creatinine clearance
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)	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)	The area under the plasma concentration-time curve calculated to the end of the dosing interval (hr\*ng/mL)
Observed Minimum Concentration After Drug Administration (Ctrough)	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)	The concentration that is just prior to the beginning of, or at the end, of a dosing interval (ng/mL)
Summary of Change From Baseline Complement C3 Biomarker in Serum	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84	To assess the effect of LNP023 on alternative complement pathway hyperactivity.
Ratio to Baseline Summary of Plasma Bb	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84	To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Newcastle Upon Tyne, United Kingdom