Long-term Efficacy, Safety and Tolerability of Iptacopan in C3G or IC-MPGN
- Conditions
- Idiopathic Immune-complex-membranoproliferative GlomerulonephritisC3 Glomerulopathy
- Interventions
- Drug: LNP023
- Registration Number
- NCT03955445
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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
- 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 up to 12 months. These longer term efficacy 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 66 months), 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".
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 183
- Patients must have completed the treatment period of the CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study drug
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort B: participants with transplanted kidneys from CLNP023X2202 LNP023 C3G participants from study CLNP023X2202 who have undergone kidney transplant and have recurrence of C3G receiving iptacopan capsules 200 mg b.i.d Cohort C: Participants with native C3G from CLNP023B12301 randomized to placebo LNP023 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 Cohort F: participants with IC-MPGN from CLNP023B12302 randomized to ipatocan LNP023 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 Cohort A: participants with native kidneys from CLNP023X2202 LNP023 C3G participants from study CLNP023X2202 with native kidneys receiving iptacopan capsules 200 mg b.i.d Cohort D: particpants with native C3G from CLNP023B12301 randomised to iptacopan LNP023 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 Cohort E: participants with IC-MPGN from CLNP023B12302 randomized to placebo LNP023 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
- Primary Outcome Measures
Name Time Method Number of participants with study drug discontinuation due to an AE (or any safety issue) Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants (adults and adolescents) from CLNP023B12301 or CLNP023B12302 Number of participants with study drug discontinuation due to an AE to evaluate the long-term safety and tolerability of iptacopan in participants.
CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint 9-month visit 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.
Number of AEs of special interest Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants (adults and adolescents) from CLNP023B12301 or CLNP023B12302 Number of participants with AEs of special interest will be collected to evaluate the long-term safety and tolerability of iptacopan in participants.
Number of participants with abnormal clinically significant vital signs,ECGs, and safety laboratory measurements Up to 66 months for participants from CLNP023X2202 and up to 36 months for participants (adults and adolescents) from CLNP023B12301 or 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.
CLNP023X2202 Cohort B - kidney transplant and recurrent C3G: Change from baseline in the C3 Deposit Score 6 - to 9- month visit Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.
- Secondary Outcome Measures
Name Time Method CLNP023X2202: Change from baseline in estimated glomerular filtration rate (eGFR) 9-month visit and up to 66 months 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
CLNP023X2202: Plasma LNP023 concentration up to 12 months at trough 3-months, 6-months, 9-months and 12-months visits Measurement of LNP023 plasma concentration to evaluate the pharmacokinetics of iptacopan in participants with prolonged treatment
CLNP023X2202: Change from baseline in log-transformed urine albumin/creatinine ratio (UACR) 3 month visit, 9-month visit and up to 66 months 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)
CLNP023X2202: Status of C3G disease progression 6 to 9 month visit 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
CLNP023X2202: Number of participants who achieve the 2-component composite renal endpoint 9-month visit 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.CLNP023X2202: Change from baseline in serum creatinine concentration 9-month visit and up to 66 months 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
CLNP023X2202: Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) 3 month visit, 9-month visit and up to 66 months 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)
CLNP023X2202: Number of participants who achieve the composite renal endpoint Up to 66 months 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.
CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time. Up to 36 months 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
CLNP023B12301 and CLNP023B12302: Number of participants who achieve a 2-component composite renal endpoint Up to 36 months 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.
CLNP023X2202: Log-transformed ratio to baseline in serum C3 9-month visit and up to 66 months Long-term effect of LNP023 on son C3 at the 9-month visit by evaluating the Log-transformed ratio to baseline in serum C3
CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in eGFR over time. Up to 36 months 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
Trial Locations
- Locations (4)
University of Iowa Health Care
🇺🇸Iowa City, Iowa, United States
Georgia Nephrology Research Inst
🇺🇸Lawrenceville, Georgia, United States
Col Uni Med Center New York Presby
🇺🇸New York, New York, United States
Novartis Investigative Site
🇬🇧Newcastle upon Tyne, United Kingdom