Long-term Efficacy, Safety and Tolerability of LNP023 in C3G

An Open-label, Non-randomized Extension Study to Evaluate the Long-term Efficacy, Safety and Tolerability of LNP023 in Subjects With C3 Glomerulopathy

This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of LNP023 in subjects with C3 glomerulopathy

Study Overview

• Status: Recruiting
• Conditions: C3 Glomerulopathy
• Intervention / Treatment: Drug: LNP023

Detailed Description

The 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 C3 glomerulopathy (C3G) Phase II study CLNP023X2202 or the C3G Phase III study CLNP023B12301. 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) afforded the opportunity to evaluate the effects of iptacopan on potential endpoint(s) for the Phase III trial in C3G at 12 months of treatment. In addition, the enrollment of participants from study CLNP023B12301 permits longer-term evaluation of the persistence of effects observed after 6 months (CLNP023B12301 patients randomised to placebo arm) or 12 months (CLNP023B12301 patients randomised to iptacopan arm) of iptacopan treatment. These longer term efficacy assessments may be compared to historical/concurrent control data available from relevant real world databases in C3G patients and used as supportive information for registration purposes. The extension study is expected to continue until the drug product becomes commercially available and accessible (anticipated to be up to approximately 66 months), or the benefit-risk profile is no longer positive, or the program is discontinued for business or strategic reasons.

Study CLNP023X2202 has enrolled C3G patients with native kidney disease (Cohort A) and C3G patients who have undergone kidney transplant and have recurrence of C3G (Cohort B); CLNP023B12301 will only enroll patients with native kidneys.

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

• Study Type: Interventional
• Enrollment (Estimated): 94
• 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
• Brazil
  • SP
    • São Paulo, SP, Brazil, 04038-002
      • Recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100034
    • Recruiting
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Recruiting
    • Novartis Investigative Site
• France
  • Montpellier, France, 34295
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75015
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Erlangen, Germany, 91054
    • Recruiting
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
• Greece
  • Heraklion Crete, Greece, 711 10
    • Recruiting
    • Novartis Investigative Site
• Israel
  • Petach Tikva, Israel, 4941492
    • Recruiting
    • Novartis Investigative Site
  • Petach-Tikva, Israel, 49202
    • Recruiting
    • Novartis Investigative Site
• Italy
  • BG
    • Ranica, BG, Italy, 24020
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00165
      • Recruiting
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466 8560
      • Recruiting
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa-city, Hokkaido, Japan, 078-8510
      • Recruiting
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 060-8543
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Recruiting
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Active, not recruiting
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06500
    • Recruiting
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0NN
    • Recruiting
    • Novartis Investigative Site
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Novartis Investigative Site
• United States
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Recruiting
      • Novartis Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Patients must have completed the treatment period of the CLNP023X2202 or CLNP023B12301 trial 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

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

3

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 LNP023 capsules 200 mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort B: participants with transplanted kidneys from CLNP023X2202; C3G participants from study CLNP023X2202 who have undergone kidney transplant and have recurrence of C3G receiving LNP023 capsules 200 mg b.i.d	Drug: LNP023; LNP023 capsules; Other Names: iptacopan
Experimental: Cohort C: Participants with native C3G from CLNP023B12301; Participants from CLNP023B12301 study receiving LNP023 capsules 200 mg 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	Number of participants with AEs of special interest will be collected to evaluate the long-term safety and tolerability of iptacopan in participants with C3G	Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants from CLNP023B12301
Number of participants with study drug discontinuation due to an AE (or any safety issue)	Number of participants with study drug discontinuation due to an AE to evaluate the long-term safety and tolerability of iptacopan in participants with C3G	Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants from CLNP023B12301
Number of participants with abnormal clinically significant vital signs,ECGs, and safety laboratory measurements	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 with C3G	Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants from CLNP023B12301

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: 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)	3 month visit, 9-month visit and up to 66 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)	3 month visit, 9-month visit and up to 66 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 at 9 months visit compared to CLNP023X2202 baseline	9-month visit and up to 66 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 at 9 months visit compared to CLNP023X2202 baseline	9-month visit and up to 66 months
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: Log-transformed ratio to baseline in serum C3	Long-term effect of LNP023 on son C3 at the 9-month visit by evaluating the Log-transformed ratio to baseline in serum C3	9-month visit and up to 66 months
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
CLNP023B12301: Change from baseline in log-transformed UPCR over time by treatment groups	Change from baseline in log-transformed UPCR will be assessed to evaluate the long-term effect of iptacopan on proteinuria	Up to 36 months
CLNP023B12301: Change from Day 180 in log-transformed UPCR over time (placebo arm of study CLNP023B12301)	Change from Day 180 in study CLNP023B12301 in log transformed UPCR will be assessed to evaluate the long-term effect of iptacopan on proteinuria	Up to 36 months
CLNP023B12301: Change from baseline in eGFR over time	Change from baseline in eGFR will be assessed to evaluate the long-term effect of iptacopan on eGFR	Up to 36 months
CLNP023B12301: Change from Day 180 in study CLNP023B12301 in eGFR over time (placebo arm of study CLNP023B12301)	Change in eGFR over time will be assessed to evaluate the long-term effect of iptacopan on eGFR	Up to 36 months
CLNP023B12301: 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 baseline visit) and UPCR (≥50% reduction in UPCR compared to the baseline visit) criteria assessed at a visit. The rate will be evaluated over time.	Up to 36 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): October 31, 2024
• Study Completion (Estimated): December 1, 2028

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 (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: LNP023; iptacopan; C3G (C3 glomerulopathy); C3GN (C3 glomerulonephritis); DDD (dense deposit disease)
• Other Study ID Numbers: CLNP023B12001B; 2018-004253-24 (EudraCT 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