Long-term Efficacy, Safety and Tolerability of Iptacopan in C3G or IC-MPGN

An Open-label, Non-randomized Extension Study to Evaluate the Long-term Efficacy, Safety and Tolerability of Iptacopan (LNP023) in C3 Glomerulopathy or Idiopathic Immune-complex-membranoproliferative Glomerulonephritis

This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of iptacopan in subjects with C3 glomerulopathy or idiopathic immune-complex-membranoproliferative glomerulonephritis

Study Overview

• Status: Recruiting
• Conditions: C3 Glomerulopathy; Immune-complex-membranoproliferative Glomerulonephritis
• Intervention / Treatment: Drug: LNP023

Detailed Description

The primary purpose of this extension study is to collect long-term efficacy, safety and tolerability data in eligible participants receiving open-label iptacopan after completing treatment in the C3G Phase 2 proof of concept study CLNP023X2202.

The primary (at 9 months) and longer-term (>9 months) efficacy and safety data of iptacopan collected from CLNP023X2202 participants will be used to support health authority submissions.

This umbrella protocol will also allow:

• continued access to iptacopan to patients enrolled in the ongoing Phase 3 programs (C3G and IC-MPGN)
• C3G study (CLNP023B12301): adults and adolescents
• IC-MPGN study (CLNP023B12302): adults and adolescents
• provision of additional efficacy and safety information following longer-term treatment in C3G and IC-MPGN populations to support health authority submissions.

Efficacy and safety assessments at the 9 month visit of this extension study in combination with data from CLNP023X2202 (baseline plus 3 months of treatment) allowed evaluation of the effects of iptacopan on potential endpoint(s) at 12 months of iptacopan treatment in C3G participants. The enrollment of C3G and IC-MPGN participants (adults and adolescents) from Phase 3 studies, CLNP023B12301 and CLNP023B12302, permits longer-term evaluation of the persistence of effects observed after iptacopan treatment. These longer term efficacy and safety assessments may be compared to historical/concurrent control data available from relevant real world databases in C3G or IC-MPGN patients and used as supportive information for registration purposes.

This extension study is expected to continue until the drug product becomes commercially available and accessible (anticipated to be up to approximately 168 months from the first patient first visit date), or the benefit-risk profile is no longer positive, or the program is discontinued for business or strategic reasons.

"Baseline" refers to the Day 1 visit (pre-dose) of CLNP023X2202, CLNP023B12301 or CLNP023B12302, whereas the Day 1 visit for this C3G/IC-MPGN extension study (CLNP023B12001B) is identified as "Extension Day 1".

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires, Argentina, W3400ABH
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1425AGC
      • Recruiting
      • Novartis Investigative Site
• Brazil
  • Salvador, Brazil, 40323-010
    • Recruiting
    • Novartis Investigative Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Recruiting
      • Novartis Investigative Site
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50740-900
      • Recruiting
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-074
      • Recruiting
      • Novartis Investigative Site
  • São Paulo
    • Botucatu, São Paulo, Brazil, 3880-1001
      • Recruiting
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 04038-002
      • Recruiting
      • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Active, not recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100034
    • Recruiting
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Recruiting
    • Novartis Investigative Site
• Czechia
  • Prague, Czechia, 128 08
    • Active, not recruiting
    • Novartis Investigative Site
• France
  • Montpellier, France, 34295
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75015
    • Recruiting
    • Novartis Investigative Site
  • Toulouse, France, 31054
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Erlangen, Germany, 91054
    • Active, not recruiting
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Recruiting
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Recruiting
    • Novartis Investigative Site
• Greece
  • Heraklion Crete., Greece, 715 00
    • Recruiting
    • Novartis Investigative Site
  • Thessaloniki, Greece, 546 42
    • Recruiting
    • Novartis Investigative Site
• Israel
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Novartis Investigative Site
  • Petah Tikva, Israel, 4920235
    • Recruiting
    • Novartis Investigative Site
• Italy
  • Roma, Italy, 165
    • Recruiting
    • Novartis Investigative Site
  • BG
    • Ranica, BG, Italy, 24020
      • Recruiting
      • Novartis Investigative Site
• Japan
  • Niigata, Japan, 9518520
    • Active, not recruiting
    • Novartis Investigative Site
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4668560
      • Active, not recruiting
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 0788510
      • Active, not recruiting
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 0608543
      • Completed
      • Novartis Investigative Site
  • Osaka
    • Takatsuki, Osaka, Japan, 5691192
      • Active, not recruiting
      • Novartis Investigative Site
  • Shiga
    • Ohtsu, Shiga, Japan, 5202192
      • Recruiting
      • Novartis Investigative Site
  • Tokyo
    • Hachiōji, Tokyo, Japan, 193-0998
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Recruiting
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Recruiting
    • Novartis Investigative Site
  • Seville, Spain, 41009
    • Recruiting
    • Novartis Investigative Site
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Kocaeli
    • Köseköy, Kocaeli, Turkey (Türkiye), 41380
      • Recruiting
      • Novartis Investigative Site
  • Melikgazi
    • Kayseri, Melikgazi, Turkey (Türkiye), 38039
      • Recruiting
      • Novartis Investigative Site
  • Yenimahalle
    • Ankara, Yenimahalle, Turkey (Türkiye), 06500
      • Recruiting
      • Novartis Investigative Site
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Novartis Investigative Site
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
      • Recruiting
      • Novartis Investigative Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Childrens Hospital Colorado
      • Principal Investigator: Bradley Dixon
      • Contact: Kati Dugan; Phone Number: +1 720 777 6895; Email: Kati.Dugan@childrenscolorado.org
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Recruiting
      • Georgia Nephrology Research Inst
      • Principal Investigator: James A Tumlin
      • Contact: Lisa Franklin; Phone Number: +1 404 645 7850#3024; Email: lfranklin@ganephrology.com
  • Iowa
    • Iowa City, Iowa, United States, 52242-1091
      • Recruiting
      • University of Iowa Health Care
      • Principal Investigator: Carla Nester
      • Contact: Nicole Gerot; Phone Number: +1 319 335 7555; Email: nicole-gerot@uiowa.edu
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Principal Investigator: Nattawat Klomjit
      • Contact: Brady Wallner; Email: walln080@umn.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Col Uni Med Center New York Presby
      • Principal Investigator: Andrew S Bomback
      • Contact: Brianna Ortiz; Phone Number: +1 212 304 5684; Email: bo2323@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Patients must have completed the treatment period of the CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study drug

Exclusion Criteria:

• Severe concurrent co-morbidities, e.g. advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating LNP023 or complying with the requirements of the study
• Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to screening, or the presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects
• History of HIV or any other immunodeficiency disease

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: participants with native kidneys from CLNP023X2202; C3G participants from study CLNP023X2202 with native kidneys receiving iptacopan capsules 200 mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort B: participants with transplanted kidneys and recurrent C3G from CLNP023X2202; C3G participants from study CLNP023X2202 who have undergone kidney transplant and have recurrence of C3G receiving iptacopan capsules 200 mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort C: Participants with native C3G randomized to placebo in CLNP023B12301; Native C3G Participants (adults and adolescents) from CLNP023B12301 study who were randomized to placebo in the core study receiving iptacopan capsules 200mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort D: particpants with native C3G randomised to iptacopan in CLNP023B12301; Native C3G participants (adults and adolescents) from study CLNP023B12301 who were randomized to iptacopan in the core study. Receiving iptacopan capsules 200mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort E: participants with IC-MPGN randomized to placebo in CLNP023B12302; IC-MPGN participants (adults and adolescents) from study CLNP023B12302 who were randomized to placebo in the core study receiving iptacopan capsules 200mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort F: participants with IC-MPGN randomized to ipatocan in CLNP023B12302; IC-MPGN participants (adults and adolescents) from study CLNP023B12302 who were randomized to iptacopan in the core study receiving iptacopan capsules 200mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint	A participant meets the requirements of the composite renal endpoint if they satisfy the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as not meeting the endpoint.	9-month visit
CLNP023X2202 Cohort B - kidney transplant and recurrent C3G: Change from baseline in the C3 Deposit Score	Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.	6 - to 9- month visit
Number of AEs of special interest for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302	Number of participants with AEs of special interest will be collected to evaluate the long-term safety and tolerability of iptacopan in participants.	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
Number of participants with study drug discontinuation due to an AE (or any safety issue) for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302	Number of participants with study drug discontinuation due to an AE to evaluate the long-term safety and tolerability of iptacopan in participants.	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
Number of participants with abnormal clinically significant vital signs,ECGs, and safety laboratory measurements for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302	Number of participants with abnormal clinically significant vital signs, ECGs, and safety laboratory measurements to evaluate the long-term safety and tolerability of iptacopan in participants.	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CLNP023X2202: Number of participants who achieve the 2-component composite renal endpoint	A participant is defined as achieving the composite renal endpoint if they meet the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR. Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.	9-month visit
CLNP023X2202: Status of C3G disease progression	Describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6 to 9 months from entry to the study compared to those obtained prior to treatment in the CLNP023X2202 study	6 to 9 month visit
CLNP023X2202: Number of participants who achieve the composite renal endpoint	A participant is defined as achieving the composite renal endpoint if they meet the following criteria at times >9 months in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.	Up to 66 months
CLNP023X2202: Plasma LNP023 concentration up to 12 months at trough	Measurement of LNP023 plasma concentration to evaluate the pharmacokinetics of iptacopan in participants with prolonged treatment	3-months, 6-months, 9-months and 12-months visits
CLNP023X2202: Change from baseline in log-transformed urine protein/creatinine ratio (UPCR)	Long-term effect of LNP023 on renal function in C3G subjects by assessing the change from baseline in log-transformed urine protein/creatinine ratio (UPCR)	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023X2202: Change from baseline in log-transformed urine albumin/creatinine ratio (UACR)	Long-term effect of LNP023 on renal function in C3G subjects by assessing the change from baseline in log-transformed urine albumin/creatinine ratio (UACR)	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023X2202: Change from baseline in serum creatinine concentration	Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in serum creatinine compared to CLNP023X2202 baseline	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023X2202: Change from baseline in estimated glomerular filtration rate (eGFR)	Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in eGFR compared to CLNP023X2202 baseline	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023X2202: Log-transformed ratio to baseline in serum C3	Long-term effect of LNP023 on C3 by evaluating the Log-transformed ratio to baseline in serum C3	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.	Change from initiation of iptacopan treatment in the core study in log-transformed UPCR will be assessed to evaluate the long-term effect of iptacopan on proteinuria	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in eGFR over time.	Change from initiation of iptacopan treatment in the core study in eGFR over time will be assessed to evaluate the long-term effect of iptacopan on eGFR	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
CLNP023B12301 and CLNP023B12302: Number of participants who achieve a 2-component composite renal endpoint	A participant is defined as meeting the requirements of the composite renal endpoint if they satisfy the eGFR (a stable or improved eGFR, i.e., ≤15% reduction in eGFR compared to the initiation of iptacopan treatment in the core study) and UPCR (≥50% reduction in UPCR compared to the initiation of iptacopan treatment in the core study) criteria assessed at a visit. Initiation of any complement pathway modifying agent or initiation/intensification of corticosteroid or immunosuppressant therapy, or renal replacement therapy automatically designates the participant as not having met the endpoint. The rate will be evaluated over time.	Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Estimated): May 30, 2036
• Study Completion (Estimated): May 30, 2036

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: DDD; LNP023; C3 glomerulopathy; C3G; dense deposit disease; C3GN; iptacopan; IC-MPGN; C3 glomerulonephritis; idiopathic immune-complex- membranoproliferative glomerulonephritis
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, Membranoproliferative; iptacopan
• Other Study ID Numbers: CLNP023B12001B; 2018-004253-24 (EudraCT Number); 2023-509343-27-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No