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
概览
- 阶段
- 3 期
- 干预措施
- LNP023
- 疾病 / 适应症
- 未指定
- 发起方
- Novartis Pharmaceuticals
- 入组人数
- 225
- 试验地点
- 57
- 主要终点
- CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint
- 状态
- 招募中
- 最后更新
- 18天前
概览
简要总结
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
详细描述
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".
研究者
入排标准
入选标准
- •\- Patients must have completed the treatment period of the CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study drug
排除标准
- •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
研究组 & 干预措施
Cohort A: participants with native kidneys from CLNP023X2202
C3G participants from study CLNP023X2202 with native kidneys receiving iptacopan capsules 200 mg b.i.d
干预措施: LNP023
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
干预措施: LNP023
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
干预措施: LNP023
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
干预措施: LNP023
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
干预措施: LNP023
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
干预措施: LNP023
结局指标
主要结局
CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint
时间窗: 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.
CLNP023X2202 Cohort B - kidney transplant and recurrent C3G: Change from baseline in the C3 Deposit Score
时间窗: 6 - to 9- month visit
Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.
Number of AEs of special interest for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
时间窗: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
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 study drug discontinuation due to an AE (or any safety issue) for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
时间窗: 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 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 for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
时间窗: 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 to evaluate the long-term safety and tolerability of iptacopan in participants.
次要结局
- CLNP023X2202: Number of participants who achieve the 2-component composite renal endpoint(9-month visit)
- CLNP023X2202: Number of participants who achieve the composite renal endpoint(Up to 66 months)
- CLNP023X2202: Plasma LNP023 concentration up to 12 months at trough(3-months, 6-months, 9-months and 12-months visits)
- CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.(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 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)(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(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)(Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months)
- CLNP023X2202: Status of C3G disease progression(6 to 9 month visit)
- CLNP023X2202: 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 eGFR over time.(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(Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months)