A Multicenter Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan in Adult Participants With Primary IgA Nephropathy Who Have Completed Study CLNP023X2203 or CLNP023A2301
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 448
- 试验地点
- 169
- 主要终点
- Number and percentage of participants with adverse events of special interest
研究概览
简要总结
The purpose of this study is to evaluate the long-term safety and tolerability, of open label iptacopan in primary IgA nephropathy participants who have completed either the CLNP023X2203 or CLNP023A2301 clinical trials. The open-label design of the current study is appropriate to provide study participants the opportunity to receive treatment with iptacopan until marketing authorizations are received and the drug product becomes commercially available while enabling collection of long-term safety and tolerability data for the investigational drug. Furthermore efficacy assessments conducted every 6 months will afford the opportunity to evaluate the clinical effects of iptacopan on long-term disease progression.
详细描述
This is an open-label, non-randomized, multicenter roll-over extension program (REP) to:
- CLNP023X2203, a Phase II trial investigating the dose ranging effects of LNP023 on efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability in primary IgAN patients, and
- CLNP023A2301, a Phase III trial, investigating the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of LNP023 in patients with primary IgAN.
Subjects completing the CLNP023X2203 and CLNP023A2301 trials on study drug, who want to continue treatment and who meet the inclusion/exclusion requirements of the roll over extension program, will have the opportunity to receive iptacopan until:
- 3 years from LPFV of this study CLNP023A2002B, or
- the participant no longer derives benefit from iptacopan according to the Investigator, or
- the benefit-risk profile of the product in IgAN is no longer positive, or
- initiation of maintenance hemodialysis, kidney transplantation or eGFR < 15 mL/min/1.73m2 , or
- the product becomes commercially available in a specific country following product launch and subsequent reimbursement for IgAN, where applicable, or
- if a marketing application or reimbursement of an investigational product is rejected/not pursued in a region/country for the indication under study or which ever is sooner
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For LNP023X2203, participants must have completed part 1 or part 2 of the trial. For LNP023A2301, participants must have completed the entire core trial defined as the full 24 month treatment period.
- •eGFR* ≥ 20 ml/min/1.73m2
- •*eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)
- •Per investigator's clinical judgement, the participant may benefit from receiving the open-label treatment of iptacopan 200 mg b.i.d.
- •Prior Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e. any boosters required administered according to local regulations.
- •All participants must be on supportive care regimen of ACEi or ARB* as per KDIGO guidelines.
- •participants who are not taking KDIGO guideline doses because they have documented allergies or intolerance to ACEi and ARB are eligible for the study
排除标准
- •participants who screen or baseline failed in the CLNP023X2203 Part 1 or Part 2, or CLNP023A2301 studies or who prematurely withdrew from either study for any reason.
- •Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with LNP
- •Current (within 4 weeks of study drug administration in the REP) acute kidney injury (AKI)
- •Presence of Rapidly Progressive Glomerulonephritis (RPGN) as defined by 50% decline in eGFR within the last 3 months.
- •Participants treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus and/or systemic corticosteroids exposure (>7.5 mg/d prednisone/prednisolone equivalent) within 5 half-lives of respective medication or 90 days prior to first study drug administration, whichever is shorter. Rituximab requires 180 days wash out.
- •Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment or within 30 days whichever is longer.
- •History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
研究组 & 干预措施
LNP023
All participants are receiving 200 mg b.i.d
干预措施: LNP023 (Drug)
结局指标
主要结局
Number and percentage of participants with adverse events of special interest
时间窗: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual adminstration of study treatment
Summary statistics on adverse events of special interest
Number and percentage of participants with abnormalities in clinical laboratory evaluations
时间窗: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Summary statistics on abnormalities in clinical laboratory evaluations
Number and percentage of participants with adverse event
时间窗: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Summary statistics on adverse events
Number and percentage of participants with serious adverse event
时间窗: Date of first administration of (Day 1) to 7 days after the date of the last actual administration of study treatment
Summary statistics on serious adverse events
Number and percentage of participants with abnormalities in vital signs
时间窗: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Summary statistics on abnormalities in vital sign parameters
Number and percentage of participants with abnormalities in ECG
时间窗: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Summary statistics in abnormalities in ECG parameters
次要结局
- Annualized total eGFR slope(Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter)
- Change from baseline in eGFR(Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter)
- Log transformed ratio to baseline in UPCR, UACR(Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter)