C3 Glomerulopathy Patient Characteristics and Treatment Response to Iptacopan in Routine Care: Analysis of Medical Charts (CHART-C3G)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 83
- 主要终点
- Demographics: Number of patients by age
研究概览
简要总结
This is a non-interventional chart abstraction cohort study with longitudinal follow up. Patients with C3G treated with iptacopan will be enrolled and characterized (i.e., systematically describe and summarize) regarding their medical history and iptacopan use and evaluated for clinical events, outcomes, and laboratory measurements upon and after iptacopan treatment initiation. Medical charts will be used to obtain secondary pseudonymized patient-level data with reference to 2 time anchors: at index date (date of iptacopan treatment initiation) with baseline covering 12 months prior to index date, and at 12-month follow-up (twelve months after the index date).The observation period includes baseline plus follow-up.
Iptacopan will be used as prescribed by the clinician in accordance with the terms of the marketing authorization. This Novartis-sponsored study, mainly executed by a contract research organization (CRO), will use secondary data from EHR obtained through reference centers/ centers of excellence in glomerular diseases in Germany.
The primary objective of this study is to characterize the demographic and clinical profiles of adult patients diagnosed with C3G upon iptacopan treatment initiation.
详细描述
Until recently, there are no approved disease-specific treatments for C3G, although there is significant interest in the therapeutic potential of complement inhibition.
Iptacopan, the first oral effective targeted disease-modifying proximal complement inhibitor developed by Novartis, has been approved in April 2025 for the treatment of adults with C3G.
The primary objective of this study is to characterize the demographic and clinical profiles of adult patients diagnosed with C3G upon iptacopan treatment initiation.
By analyzing key endpoints such as age, sex, ethnicity, BMI, clinical symptoms, proteinuria, blood pressure, serum creatinine, eGFR, serum C3 levels, and renal histological parameters, we aim to better understand disease progression and treatment outcomes.
Additionally, we will assess CKD stages, history of kidney failure, dialysis status, transplant status, and comorbidities to identify the characteristics of patients treated with iptacopan.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Clinical diagnosis of C3G (confirmed by biopsy, only if available)
- •Aged ≥18 years at time of index date.
- •At least 6 months of baseline period preceding index date.
- •Users of iptacopan treatment including those who have discontinued iptacopan within the last twelve weeks.
排除标准
- •Interventional C3G clinical trial participation
研究组 & 干预措施
Iptacopan
Adult patients with C3G initiating iptacopan treatment in routine care
干预措施: Iptacopan (Other)
结局指标
主要结局
Demographics: Number of patients by age
时间窗: Baseline
Age at baseline in years
Demographics: Body mass index
时间窗: Baseline
Body mass index reported at baseline, or the closest value before baseline. In the absence of records for body mass index, it can be calculated using records of height and weight.
Demographics: Number of patients by sex
时间窗: Baseline
Female Male
Demographics: Number of patients by site
时间窗: Baseline
Academic hospital Other sites
Albuminuria - Number of participants by spot uACR
时间窗: Baseline
No Yes
Demographics: Number of patinets with Biopsy confirming C3G
时间窗: Baseline
No Yes
Clinical symptoms: Proteinuria - Number of participants by 24-hour uPCR
时间窗: Baseline
No Yes 24-hour uPCR \< 1 g/g 24-hour uPCR ≥ 1 g/g
Proteinuria - Number of participants by spot uPCR
时间窗: Baseline
No Yes Spot uPCR \< 1 g/g Spot uPCR ≥ 1 g/g
Proteinuria, 24-hour uPCR in g/g
时间窗: Baseline
Absolute value of uPCR based on a 24-hour urine collection
Proteinuria, spot uPCR in g/g
时间窗: Baseline
Absolute value of uPCR based on a spot urine collection
Clinical symptoms: Albuminuria
时间窗: Baseline
No Yes
Albuminuria, 24-hour uACR in g/g
时间窗: Baseline
Absolute value of uACR based on a 24-hour urine collection
Albuminuria, spot uACR in g/g
时间窗: Baseline
No Yes
Clinical symptoms: Number of participants by Hematuria - dipstick results
时间窗: Baseline
No Yes Microscopic (≥3RBCs/HPF) Macroscopic (visible to the naked eye)
Hematuria - Number of participants by urinalysis results
时间窗: Baseline
0-2 red blood cells ≥3 red blood cells
Hematuria - urinalysis, number of red blood cells
时间窗: Baseline
Number of red blood cells detected through urinalysis
Clinical symptoms: Computed eGFR at baseline
时间窗: Baseline
eGFR computed in the study analysis
Clinical symptoms: Serum C3 at baseline
时间窗: Baseline
Reference range: LLN = 4.33-5.00 μmol/L ULN = 9.05-11.16 μmol/L
Clinical symptoms: Number of participants with presence of edema
时间窗: Baseline
Presence of edema. No Yes
Clinical symptoms: Systolic and diastolic blood pressure
时间窗: Baseline
Blood pressure measurement
Clinical symptoms: Number of participants with hypertension
时间窗: Baseline
Defined as systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg No Yes
Clinical symptoms: Serum creatinine at baseline
时间窗: Baseline
Absolute value of serum creatinine
Clinical symptoms: Reported eGFR at baseline
时间窗: Baseline
Based on medical records of eGFR
Clinical symptoms: Number of participants by equation used in reported eGFR at baseline
时间窗: Baseline
2021 CKD-EPI creatinine 2021 CKD-EPI creatinine-cystatin C 2012 CKD-EPI cystatin C 2012 CKD-EPI creatinine-cystatin C 2009 CKD-EPI creatinine MDRD (based on creatinine) Cockroft-Gault (based on creatinine) Schwartz equation (based on creatinine) Not specified
Clinical events and outcomes: Time since C3G diagnosis (days/months)
时间窗: Baseline
Time since the first C3G diagnosis to baseline
Clinical events and outcomes: Number of participants with Chronic Kidney Disease (CKD) and stage
时间窗: Baseline
No Yes Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
Clinical events and outcomes: Number of participants with history of kidney failure
时间窗: Baseline
No Yes (either of the categories below) eGFR ≤ 15 History of dialysis History of kidney transplant
Clinical events and outcomes: Number of participants by dialysis status
时间窗: Baseline
No Yes Dialysis at diagnosis of C3G Maintenance dialysis Other types
Clinical events and outcomes: Time from C3G diagnosis to dialysis (months)
时间窗: Baseline
Concerns only patients with dialysis at or before baseline
Clinical events and outcomes: Time from dialysis to baseline (months)
时间窗: Baseline
Concerns only patients with dialysis at or before baseline
Clinical events and outcomes: Number of participants by transplant status at baseline
时间窗: Baseline
No (native kidney) Yes Biopsy-confirmed disease in native kidney No evidence of disease recurrence Recurrent disease in transplanted kidney
Clinical events and outcomes: Time from C3G diagnosis to kidney transplant before baseline (months)
时间窗: Baseline
Concerns only patients with a kidney transplant (or kidney transplant failure) at or before baseline
Clinical events and outcomes: Time from kidney transplant before baseline to baseline (months)
时间窗: Baseline
Concerns only patients with a kidney transplant (or kidney transplant failure) at or before baseline
Clinical events and outcomes: Number of participants with C3G disease recurrence post-transplant and/or transplant failure
时间窗: Baseline
Concerns only patients with a kidney transplant (or kidney transplant failure) at or before baseline. No Yes
Clinical events and outcomes: Number of participants with comorbidities
时间窗: Baseline
For example, history of heart failure, history of stroke, diabetes mellitus, dementia, malignancy
Renal histopathological parameters: Number of participants with presence of cysts
时间窗: Baseline
No Yes
Renal histopathological parameters: Number of participants with presence of tumors
时间窗: Baseline
No Yes
Renal histopathological parameters: Number of participants with presence of interstitial fibrosis or tubular atrophy
时间窗: Baseline
Mild Moderate Severe
Renal histopathological parameters: Number of participants with presence of glomerulosclerosis
时间窗: Baseline
Mild Moderate Severe
Renal histopathological parameters: Endocapillary hypercellularity
时间窗: Baseline
Presence of cells in capillary loops with loop occlusion 0 = 0% (Essentially normal or no lesion) 1. = 1-25% (Only a small fraction of loops are occluded by hypercellularity) 2. = 26-50% (About one-quarter to half of the loops show occlusion) 3. = ≥51% (More than half of the loops are occluded, indicating extensive endocapillary proliferation)
Renal histopathological parameters: Neutrophils in capillary lumens (each glomerulus is scored)
时间窗: Baseline
0 = 0% (No neutrophils in any capillary loops of the glomerulus) 1. = 1-25% (Mild involvement: neutrophils present in up to ¼ of loops) 2. = 26-50% (Moderate involvement: neutrophils in about ¼ to half of loops) 3. = ≥51% (Severe involvement: neutrophils in more than half of loops)
Renal histopathological parameters: Mesangial hypercellularity
时间窗: Baseline
More than 4 cells in a mesangial area away from the hilum 0 = 0% (No mesangial areas with \>4 cells) 1. = 1-25% (Mild involvement: 1-25% of mesangial areas show hypercellularity) 2. = 26-50% (Moderate involvement: 26-50% of mesangial areas affected) 3. = ≥51% (Severe involvement: More than half of mesangial areas show hypercellularity)
Renal histopathological parameters: Necrosis
时间窗: Baseline
Necrosis in glomerular pathology refers to active destructive lesions characterized by: Disruption of the glomerular basement membrane (GBM) Fibrin exudation into Bowman's space or capillary loops Karyorrhexis (fragmentation of nuclei of inflammatory cells) - at least 2 of these 3 lesions need to be present to meet the criteria for necrosis. 0 = 0% (No glomeruli show necrosis) 1. = 1-10% (Mild: 1-10% of glomeruli have necrosis) 2. = 11-25% (Moderate: 11-25% of glomeruli affected) 3. = ≥25% (Severe: More than 25% of glomeruli show necrosis)
Renal histopathological parameters: Cellular or fibrocellular crescents
时间窗: Baseline
0 = 0% (No crescents in any glomeruli) 1. = 1-10% (Mild: 1-10% of glomeruli have crescents) 2. = 11-25% (Moderate: 11-25% of glomeruli affected) 3. = \>25% (Severe: More than 25% of glomeruli show crescents)
Renal histopathological parameters: Activity index
时间窗: Baseline
A score between 0 and 15, calculated by summing up the scores from the activity index parameters above (Endocapillary hypercellularity,. Neutrophils in capillary lumens, Mesangial hypercellularity, Necrosis and Cellular or fibrocellular crescents). Score 0: No active lesions. The kidney shows chronic changes only, but no ongoing inflammation. Higher score implies not aggressively active, and kidney damage is likely stable or progressing slowly.
Renal histopathological parameters: score inflammation assessment scale
时间窗: Baseline
Both continuous (score inflammation assessment scale) and categorically (none, mild, moderate, severe). Continuous Scale (Numeric Score) 1. Low score (e.g., 0-3) Minimal inflammatory activity 2. High score (e.g., ≥9) Extensive active lesions (necrosis, crescents, heavy infiltration) Categorical Scale (None, Mild, Moderate, Severe) 1. None: No significant inflammation; likely chronic or inactive disease. 2. Mild: Small, focal involvement; early or controlled disease. 3. Moderate: Widespread but not diffuse; active disease needing treatment. 4. Severe: Diffuse, aggressive inflammation; high risk of rapid progression to renal failure.
Renal histopathological parameters: Number of participants by typo of inflammation
时间窗: Baseline
Type of inflammation: none, mild, moderate, severe
Chronicity index parameters: Number of participants with glomerular (or segmental) sclerosis
时间窗: Baseline
0 = ≤10% 1. = 11-25% 2. = 26-50% 3. = ≥51%
Chronicity index parameters: Number of participants with Fibrous crescents
时间窗: Baseline
0 = none 1. = ≤25% 2. = 26-50% 3= \>51%
Chronicity index parameters: Number of participants with tubular atrophy
时间窗: Baseline
0 = ≤5% 1. = 6-25% 2. = 26-50% 3. = ≥51%
Chronicity index parameters: Number of participants with interstitial fibrosis
时间窗: Baseline
0 = ≤5% 1. = 6-25% 2. = 26-50% 3. = ≥51%
Renal histopathological parameters: Chronicity index
时间窗: Baseline
A score between 0 and 12, calculated by summing up the scores from the chronicity index parameters above (Glomerular (or segmental) sclerosis, Fibrous crescents, Tubular atrophy and Interstitial fibrosis) Lower scores indicate less chronic damage, higher scores indicate more scarring and poor prognosis. 0-3 (Minimal to Mild) → Very little irreversible damage. Prognosis is generally favorable if activity index is also low. 4-6 (Moderate) * Significant chronic changes; recovery potential is limited. 7-12 (Severe) * Extensive scarring; immunosuppression unlikely to reverse damage
次要结局
- Clinical events and outcomes: Time from baseline to first dialysis (months)(Up to 12 months)
- Clinical events and outcomes: Number of participants with kindney failure during follow-up(Up to 12 months)
- Clinical events and outcomes: Time from kidney failure to maintenance dialysis (months)(Up to 12 months)
- Clinical events and outcomes: Time from C3G diagnosis to kidney failure and time from baseline to kidney failure(Up to 12 months)
- Clinical events and outcomes: Number of participants with dialysis during follow-up(Up to 12 months)
- Clinical events and outcomes:Time from kidney failure to first dialysis (months)(Up to 12 months)
- Clinical events and outcomes: Time from C3G diagnosis to maintenance dialysis (months)(Up to 12 months)
- Clinical events and outcomes: Time from baseline to maintenance dialysis (months)(Up to 12 months)
- Clinical events and outcomes: Number of participants with complete remission (controlled) of C3G during follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants with nephrotic-range and non-nephrotic range proteinuria during follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants with renal relapse, progression to a higher CKD stage, or chronic renal replacement therapy during follow-up(Up to 12 months)
- Clinical events and outcomes: Number of transplant failures per patient during follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants with CKD and stage at 12-month follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants by transplant status at 12-month follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants with Kidney transplant during follow-up(Up to 12 months)
- Clinical events and outcomes: Time from kidney failure to transplant during follow-up (months)(Up to 12 months)
- Clinical events and outcomes: Time from transplant during follow-up to post- transplant C3G disease recurrence (months)(Up to 12 months)
- Clinical events and outcomes: Time from transplant to transplant failure (months)(Up to 12 months)
- Clinical events and outcomes: Number of participants with C3G disease recurrence post-transplant and/or transplant failure(Up to 12 months)
- Clinical events and outcomes: Time from C3G disease recurrence to transplant failure(Up to 12 months)
- Clinical events and outcomes: Time from transplant at any time to post- transplant C3G disease recurrence(Up to 12 months)
- Clinical events and outcomes: Number of participants with death during follow-up(Up to 12 months)
- Clinical events and outcomes: Number of participants by cause of Death(Up to 12 Months)
- Laboratory measurements: Serum creatinine or eGFR(6 months, 12 months and 24 months before baseline and up to 12 months follow-up)
- Laboratory measurements: Change in reported eGFR from baseline to 12-month follow-up, mL/min/1.73m(Baseline, Month 12)
- Laboratory measurements: Follow-up serum creatinine or eGFR 6 months after baseline(Up to 12 months)
- Laboratory measurements: eGFR slope during the 24months prior to baseline(24 months prior to baseline and 12 months post baseline)
- Laboratory measurements: eGFR slope during the 12 months after baseline, mL/min/1.73m²/year(Up to 12 months)
- Laboratory measurements: Equation used in reported 12-month follow-up eGFR(Month 12 follow-up)
- Laboratory measurements: Change in computed eGFR from baseline to 12-month, mL/min/1.73m(Baseline, Month 12)
- Laboratory measurements: Number of participants with Proteinuria 24-hour uPCR(Up to 12 months)
- Laboratory measurements: Proteinuria at 12-month, spot uPCR in g/g(Up to 12 months)
- Laboratory measurements: Number of participants with Proteinuria at 12-month follow-up - spot uPCR(Up to 12 months)
- Laboratory measurements: Proteinuria at 12-month follow-up, 24-hour uPCR in g/g(Up to 12 months)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up, 24-hour uPCR in g/g(Baseline, Month 12)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up, spot uPCR in g/g(Baseline, Month 12)
- Laboratory measurements: Change in hematuria from baseline to 12-month follow-up(Baseline, Month 12)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up in mg/mmol - 24-hour uPCR(Baseline, Month 12)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up in mg/mmol - spot uPCR(Baseline, Month 12)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up in g/g - 24-hour uPCR(Baseline, Month 12)
- Laboratory measurements: Change in proteinuria from baseline to 12-month follow-up in g/g - spot uPCR(Baseline, Month 12)
- Laboratory measurements: Change in albuminuria from baseline to 12-month follow-up, spot uACR in g/g(Baseline, Month 12)
- Laboratory measurements: Number of participants with albuminuria(Up to 12 months)
- Laboratory measurements: Number of participants with Albuminuria at 12-month follow-up - spot uACR(Up to 12 months)
- Laboratory measurements: Albuminuria at 12-month follow-up, 24-hour uACR in g/g(Up to 12 months)
- Laboratory measurements: Hematuria - Number of participants by urinalysis results(Up to 12 months)
- Laboratory measurements: Albuminuria at 12-month follow-up, spot uACR in g/g(Up to 12 months)
- Laboratory measurements: Change in albuminuria from baseline to 12-month follow-up, 24-hour uACR in g/g(Baseline, Month 12)
- Laboratory measurements: Hematuria - urinalysis, number of red blood cells(Up to 12 months)
- Laboratory measurements: Number of participants with Hematuria dipstick(Up to 12 months)
- Laboratory measurements: Change in hematuria on urinalysis from baseline to 12-month follow-up, number of red blood cells(Baseline, Month 12)
- Laboratory measurements: Number of participants with presence of autoantibodies(Up to month 12 follow-up)
- Laboratory measurements: CH50 and CH100(Up to month 12 follow up)
- Laboratory measurements: AH50 and AH100(Up to month 12 follow-up)
- Laboratory measurements: Wieslab activity of the alternative pathway of complement(Up to month 12 follow-up)
- Laboratory measurements: Serum C3, Serum C4 and Serum C5(Up to month 12 follow-up)
- Disease management: Missed or delayed dose of iptacopan during follow-up(Up to 12 months follow-up)
- Laboratory measurements: Fibrinogen Degradation; (FD)(Up to month 12 follow-up)
- Laboratory measurements: fragment a of complement factor B (Ba)(Up to month 12 follow-up)
- Laboratory measurements: fragment b of complement factor B (Bb)(Up to 12 months follow-up)
- Disease management: Number of participants by Iptacopan daily dose(Baseline and up to 12 months follow-up)
- Laboratory measurements: soluble terminal complement activation fragment (sC5b-9)(Up to 12 months follow-up)
- Disease management: Number of participants by status of vaccination and prophylactic antibiotic at baseline(Up to 12 months follow up)
- Disease management: Number of participants by Iptacopan daily dose change from baseline to the end of follow-up(Baseline, up to month 12 follow-up)
- Disease management: Time to first modification of iptacopan dosage (days)(Up to 12 months-follow up)
- Disease management: Number of participants by reason of modification of iptacopan dosage during follow-up(Up to 12 months follow-up)
- Disease management: Number of participants with prior use of immunosuppressive medication(Up to month 12 follow-up)
- Disease management: Time from C3G diagnosis to the first complement inhibitor before baseline(Baseline)
- Disease management: Number of participants by concomitant C3G treatments(Up to 12 months follow-up)
- Disease management: Duration of C3G treatments during follow-up(Up to 12 months follow-up)
- Disease management: Number of participants by reason of discontinuation of C3G treatments during follow-up(Up to 12 months follow-up)
- Disease management: Number of participants with antibiotic treatment related to C3G during follow- up(Up to 12 months follow-up)
- Disease management: Adherence to iptacopan treatment - PDC(Up to 12 months follow-up)
- Disease management: Number of participants by adherence to iptacopan treatment(Up to month 12 follow-up)
- Disease management: Number of participants with discontinuation of iptacopan during follow-up(Up to 12 months follow-up)
- Disease management: Time to iptacopan treatment discontinuation - TTD(Up to 12 months follow-up)
- Disease management: Number of participants with C3G treatment change after iptacopan discontinuation(Up to 12 months follow-up)
- Disease management: Numbre of participants by antibiotic treatment related to C3G during follow-up(Up to 12 months follow up)
- Disease management: Adherence to iptacopan treatment - PDC, %(Up to 12 months follow up)
- Disease management: Adherence to iptacopan treatment, n (%)(Up to 12 months follow up)
- Disease management: Number of participants discontinuing iptacopan during follow-up(Up to 12 months follow up)
- Disease management: Number of participants by reason for discontinuation of iptacopan, n (%)(Up to 12 months follow up)
- Disease management: Time to iptacopan treatment discontinuation - TTD, days(Up to 12 months follow up)
- Disease management: C3G treatment change after iptacopan discontinuation, n (%)(Up to 12 months follow up)
- Healthcare resource utilization: Number of hospitalizations during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Number of participants by cause of first hospitalization during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Length of first hospitalization during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Number of participants bu cause of first readmission after first hospitalization during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Length of first readmission after first hospitalization during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Number of hospitalizations due to infection during the 12-month period before baseline(Baseline)
- Healthcare resource utilization: Number of hospitalizations during follow-up(Up to 12 months follow-up)
- Healthcare resource utilization: Number of participants by cause of first hospitalization during follow-up(Up to 12 months follow-up)
- Healthcare resource utilization: Length of first hospitalization during follow-up(Up to 12 months follow-up)
- Healthcare resource utilization: Number of participants by cause of first readmission after first hospitalization during follow-up(Up to 12 months follow-up)
- Healthcare resource utilization: Length of first readmission after first hospitalization during follow-up(Up to 12 months follow-up)
- Healthcare resource utilization: Number of hospitalizations due to infection during follow-up(Up to 12 months follow-up)