Kidney Diseases
Conditions
Keywords
glomerulopathy
Brief summary
The study is planned to study specificity of the clinical course and treatment outcomes of C3 glomerulopathy (C3G) and Immune-complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged under 18 years and 18 years and older in the Russian population in 2025-2028. The primary objective of the study is to estimate the frequency of complete or partial remission 12 months after morphological verification of the diagnosis. Assessment of demographic, clinical and laboratory, morphological characteristics at diagnosis and their relationship with the disease outcomes, primarily the disease progression and development of chronic renal failure, will allow assessing the efficacy of treatment used in real clinical practice, disease prognosis and factors associated with unfavourable outcomes.
Interventions
OTHERNo intervention
Patients will receive medical care in accordance with the routine practice of disease treatment
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Willing to sign informed consent form. If the patient is under 18 years of age, the parent or legally acceptable representative of the child/adolescent who can participate in this study also signs the consent form. 2. Diagnosis of primary C3G or IC-MPGN confirmed by the results of morphological and clinical studies. 3. The results of serum creatinine level, proteinuria determination obtained not earlier than 4 weeks before the kidney biopsy 4. Index date (kidney biopsy) not earlier than March 2024 and not later than 11 months before signing the ICF 5. The estimated baseline GFR (using the CKD-EPI formula for persons aged over 18 years and the modified Schwarz formula for children) or the measured GFR is ≥30 mL/min per 1.73 m2.
Exclusion criteria
1. Patients participating in a clinical trial with the investigational product. 2. Patients with monoclonal gammopathies (myeloma, B-cell lymphoma/lymphocytic leukemia, lymphoplasmacytoma) 3. Patients with systemic autoimmune diseases and vasculitis (systemic lupus erythematosus, systemic sclerosis, dermatomyositis, mixed connective tissue disease, Sjogren syndrome, Henoch-Schönlein purpura, ANCA vasculitis, cryoglobulinemia) 4. Patients with current or recent infections (viral hepatitis B, viral hepatitis C, infective endocarditis or sepsis, infected ventriculoatrial shunts, abscesses, meningococcal and other bacterial infections, protozoan infections) 5. Patients with any clinically significant acute disease within 30 days prior to kidney biopsy 6. Clinically significant concomitant kidney disease 7. Treatment with pegcetacoplan Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and proportion of patients with overall (complete + partial) remission following the standard therapy in Russia | 12 months | Complete response is defined as proteinuria \<0.5 g/24 h with stable eGFR (less than 20% decline in eGFR from baseline without the need for renal replacement therapy). Partial response is defined as reduction of proteinuria at stable eGFR (no decrease of \>20% of baseline value): \>50% (from baseline) (in those with proteinuria \<3.5 g/day or \>3.5 g/day but without nephrotic syndrome (NS)) OR in ≥50% from baseline accompanied by a regression of NS (NS \<3.5 g/day and blood albumin ≥30 g/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and proportion of patients with partial remission | 6 months; 12 months | Partial remission was defined as a reduction in proteinuria at stable eGFR (no decrease of \>20% of baseline): \>50% (from baseline) (in those with proteinuria \<3.5 g/day or \>3.5 g/day but without nephrotic syndrome (NS)) OR in ≥50% from baseline accompanied by a regression of NS (NS: \<3.5 g/day and blood albumin ≥30 g/L) |
| Number and proportion of patients with relapse | 6 months; 12 months | Clinical relapse was defined as a proteinuria \>3.5 g/24h after achieving complete remission or, in those with partial remission, as an increase of proteinuria \>50% compared with the lowest value during remission with recurrence of NS |
| Number and proportion of patients with progression | 6 months; 12 months | Composite progression defined as 40% eGFR decline from the baseline and/or eGFR \<15 mL/min per 1.73 m2 and/or renal replacement therapy |
| Number and proportion of patients with progression to end-stage kidney disease | 6 months; 12 months | Number and proportion of patients with progression to end-stage kidney disease from index-date up to 12 months |
| Number and proportion of died patients | 6 months; 12 months | Number and proportion of patients who died from index date up to 12 months |
| Time to start of maintenance dialysis | 6 months; 12 months | Time in months from index date to start of maintenance dialysis |
| Time from the diagnosis date to the start date of dialysis | 6 months; 12 months | Time in months from the diagnosis date to the start date of dialysis |
| Time from the start date of treatment to the start date of dialysis | 6 months; 12 months | Time in months from first treatment date to the start date of dialysis |
| Time from the diagnosis date to transplantation | 6 months; 12 months | Time in months from the diagnosis date to transplantation |
| Time from the diagnosis date to the date of complete remission | 6 months; 12 months | Time in months from the diagnosis date to the date of complete remission |
| Time from the diagnosis date to the date of partial remission | 6 months; 12 months | Time in months from the diagnosis date to the date of partial remission |
| Time from the diagnosis date to the date of overall remission (complete and partial remission) | 6 months; 12 months | Time in months from the diagnosis date to the date of overall remission (complete and partial remission) |
| Time to progression | 6 months; 12 months | Time in months from the diagnosis date to progression |
| Number and proportion of patients with a) an increase in eGFR by ≥15% from the baseline; b) decrease in eGFR by ≥15% from the baseline; c) stable eGFR (change up to 15%) | 6 months; 12 months | Number and proportion of patients with a) an increase in eGFR by ≥15% from the baseline; b) decrease in eGFR by ≥15% from the baseline; c) stable eGFR (change up to 15%) from index date up to 12 months |
| Time to 30%, 40% and 50% decline in eGFR | 6 months; 12 months | Time in months from index date to 30%, 40% and 50% decline in eGFR |
| Number and proportion of patients with proteinuria >1 g/24 h and eGFR ≥30 mL/min per 1.73 m2 | 6 months; 12 months | Number and proportion of patients with proteinuria \>1 g/24 h and eGFR ≥30 mL/min per 1.73 m2 from index date up to 12 months |
| Number and proportion of patients with nephrotic syndrome | 6 months; 12 months | Number and proportion of patients with nephrotic syndrome from index date up to 12 months |
| Demographic and clinical characteristics of patients with primary C3G (cohort 1), IC-MPGN (cohort 2), and overall | Baseline | Number and proportion of patients by age, gender, BMI, BSA, family history of kidney disease, transplant status, blood pressure, laboratory markers: serum creatinine level (µmol/L), eGFR, urinary blood cell (RBCs/hpf), proteinuria (g/24h), serum albumin (g/L); eGFR rate of change; chronic kidney disease (CKD) stage; proteinuria ≥1 g/24 h AND eGFR ≥30 mL/min per 1.73 m2 |
| Number of patients by morphologically verified disease form in patients with primary C3G (cohort 1), IC-MPGN (cohort 2), and overall | Baseline | Morphologically verified disease form: DDD (subject to electron microscopy), C3GN (subject to electron microscopy), C3G (in the absence of informative electron microscopy data), IC-MPGN. |
| Number of patients with presence of serum complement markers, serum factor H, rare genetic variants | Baseline | Number of patients with presence of serum complement markers (C3, C4, CH50, C5a), serum factor H, rare genetic variants at baseline |
| Number and proportion of patients stratified by treatment sequence and specific regimen of treatment | Baseline; 6 months; 12 months | Number and proportion of patients stratified by treatment sequence and specific regimen of treatment |
| Number and proportion of patients that discontinued a specific regimen of treatment at each line of therapy at any time during follow-up and reason for discontinuation for each cohort | Baseline; 6 months; 12 months | Number and proportion of patients that discontinued a specific regimen of treatment at each line of therapy at any time during follow-up and reason for discontinuation for each cohort |
| Number of exposed doses for non-continuous treatments (e.g., pulse therapy, rituximab infusion) in each cohort | Baseline; 6 months; 12 months | Number of exposed doses for non-continuous treatments (e.g., pulse therapy, rituximab infusion) in each cohort |
| Number of patients by qualitative, semi-quantitative and quantitative scores of active and chronic lesions | Baseline | 1. mesangial proliferation (% of glomeruli), 2. endocapillary hypercellularity (% of glomeruli), 3. membranoproliferative morphology (thickening and/or double contouring of the capillary basement membranes), 4. leukocyte infiltration, 5. proportion of completely intact glomeruli (%) 6. proportion of cellular (%), fibrous (%), fibrocellular (%) crescents, 7. fibrinoid necrosis, 8. interstitial infiltration, 9. interstitial fibrosis (%), 10. tubular atrophy (%), 11. global and segmental glomerulosclerosis (quantitatively, % of all glomeruli) 12. arteriosclerosis and arteriolosclerosis |
| Number of patients with signs of thrombotic microangiopathy in the biopsy specimen | Baseline | Number of patients with signs of thrombotic microangiopathy in the biopsy specimen at baseline |
| Number of patients with acute tubular necrosis | Baseline | Number of patients with acute tubular necrosis at baseline |
| Number of patients with presence of C1q, IgA, IgM, IgG, C3, kappa chain, lambda chain deposits | Baseline | Number of patients with presence of C1q, IgA, IgM, IgG, C3, kappa chain, lambda chain deposits at baseline |
| Patient-reported outcomes for C3G (cohort 1), IC-MPGN (cohort 2), and overall | 12 months | 1. Descriptive adherence data based on question score 2. Patient-reported outcomes, SF-36 (RAND) |
| Number of patients (%) with adverse events/serious adverse events by treatment option | 12 months | Number of patients (%) with adverse events/serious adverse events by treatment option from index date up to 12 months |
| Change from baseline of systolic and diastolic blood pressure (BP) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline of systolic and diastolic blood pressure (BP) (with percentiles for children) at 6 and 12 month |
| Change from baseline serum creatinine level (µmol/L) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline serum creatinine level (µmol/L) at 6 and 12 months |
| Change from baseline estimated glomerular filtration rate (eGFR) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline estimated glomerular filtration rate (eGFR) at 6 and 12 months |
| Change from baseline eGFR rate of change over time (eGFR slope) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline eGFR rate of change over time (eGFR slope) at 6 and 12 months |
| Change from baseline chronic kidney disease (CKD) stage (number of patients, %) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline chronic kidney disease (CKD) stage (number of patients, %) at 6 and 12 months |
| Change from baseline red blood cell count in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline red blood cell (RBC) count at 6 and 12 months |
| Number and proportion of patients with complete remission | 6 months; 12 months | Complete remission was defined as proteinuria \<0.5 g/24 h with a stable eGFR (less than 20% decline in eGFR from baseline without the needs for renal replacement therapy). |
| Change from baseline daily proteinuria (proteinuria in g/24 hours) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline daily proteinuria (proteinuria in g/24 hours) at 6 and 12 months |
| Change from baseline proteinuria >1 g/24 h in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline proteinuria \>1 g/24 h at 6 and 12 months |
| Change from baseline eGFR ≥30 mL/min per 1.73 m2 in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline eGFR ≥30 mL/min per 1.73 m2 at 6 and 12 months |
| Change from baseline number of patients with nephrotic syndrome (%) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline number of patients with nephrotic syndrome (%) at 6 and 12 months |
| Change from baseline RBC casts in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall | 6 months; 12 months | Change from baseline RBC casts at 6 and 12 months |
Contacts
Primary ContactNovartis Pharmaceuticals
Backup ContactNovartis Pharmaceuticals
Outcome results
None listed