A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Idiopathic Immune-complex-mediated Membranoproliferative Glomerulonephritis (IC-MPGN)
概览
- 阶段
- 3 期
- 干预措施
- iptacopan
- 疾病 / 适应症
- IC-MPGN
- 发起方
- Novartis Pharmaceuticals
- 入组人数
- 106
- 试验地点
- 143
- 主要终点
- Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months.
- 状态
- 招募中
- 最后更新
- 3天前
概览
简要总结
This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.
详细描述
The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic IC-MPGN. The study aims to demonstrate a reduction in proteinuria and improvement in estimated glomerular filtration rate (eGFR) in participants treated with iptacopan compared to placebo. Change in patient-reported fatigue will also be evaluated. Alternative complement pathway (AP) dysregulation is believed to underlie the clinical manifestations and progression of IC-MPGN. Upon completion of study treatment, participants will have the option to discontinue iptacopan treatment and enter a 30 day safety follow-up or continue iptacopan treatment by transitioning to an open label extension study (CLNP023B12001B; NCT03955445) and continue iptacopan treatment.
研究者
入排标准
入选标准
- •Male and female patients including adults (aged at least 18 years to ≤ 60 years) and adolescents (12 -17 years in non-EU countries at screening and 16-17 years in EU countries at screening).
- •Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only).
- •Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin angiotensin system inhibitors (RASi), e.g an ACEi or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization
- •UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15
- •Estimated GFR (using the chronic kidney disease \[CKD\]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -
- •Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care.
- •If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration.
排除标准
- •Participants who have undergone cell or solid organ transplantation, including kidney transplantation.
- •Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions:
- •Deposition of antigen-antibody immune complexes as a result of any chronic infections, including
- •Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV);
- •Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections
- •Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis
- •Renal deposition of immune complexes as a result of a systemic autoimmune disease:
- •Systemic lupus erythematosus (SLE)
- •Sjögren syndrome
- •Rheumatoid arthritis
研究组 & 干预措施
iptacopan 200mg b.i.d
iptacopan 200mg b.i.d
干预措施: iptacopan
Placebo to iptacopan 200mg b.i.d.
Placebo to iptacopan 200mg b.i.d.
干预措施: Placebo
结局指标
主要结局
Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months.
时间窗: 6 months (double-blind)
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
Log-transformed ratio to baseline in UPCR at the 18-month visit (each study treatment arm)
时间窗: 18 months
To evaluate the effect of iptacopan on proteinuria at 18 months.
Log-transformed ratio to 12-month visit in UPCR at the 18-month visit in the placebo arm.
时间窗: 18 months
To evaluate the effect of iptacopan on proteinuria at 18 months.
次要结局
- Change from baseline in eGFR(12 months and 18 months)
- Change in eGFR from the 12-month visit to the 18- month visit of the placebo arm(18 months)
- Proportion of patients achieved a composite renal endpoint(6 and 12 months)
- Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.(12 months)
- Number of participants with abnormal vital signs, ECGs and safety laboratory measurements as well as study drug discontinuation due to an AE(up to 18 months)
- Number of participants with clinically significant changes in heart rate, blood pressure, echocardiography parameters in adolescent patients(up to 18 months)
- Annualized total eGFR slope estimated over 12 months.(12 months)
- Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 12 months.(12 months)
- Proportion of participants who achieved the composite renal endpoint at 18 months(18 months)