Clinical Outcomes of C3 Glomerulopathy and IC-MPGN in Russia: Hybrid Retrospective - Prospective Study (CRYSTAL)

February 26, 2025 updated by: Novartis Pharmaceuticals
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Novartis Pharmaceuticals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The study will recruit adults (aged 18 years and older) and pediatric patients (legally acceptable representatives) with biopsy-confirmed diagnosis of primary C3G or idiopathic IC-MPGN in the period from March 2024 to February 2027, who will meet the inclusion criteria and none of the exclusion criteria.

Description

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/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
C3 glomerulopathy
Diagnosis of primary C3G confirmed by the results of morphological and clinical studies.
Other: No intervention
Patients will receive medical care in accordance with the routine practice of disease treatment
Other Names:
  • Rituximab
  • Treatment includes the following options:
  • ACEi/ARB alone
  • ACEi/ARB + corticosteroids
  • ACEi/ARB + MMF
  • ACEi/ARB + SGLT2i
  • ACEi/ARB + MMF + corticosteroids
  • ACEi/ARB + cyclophosphamide
  • Corticosteroids alone
  • MMF alone
  • Cyclophosphamide alone
  • Corticosteroids + MMF
  • Anticomplement therapy
  • Other immunosuppressants
Immune-complex membranoproliferative glomerulonephritis
Diagnosis of primary IC-MPGN confirmed by the results of morphological and clinical studies.
Other: No intervention
Patients will receive medical care in accordance with the routine practice of disease treatment
Other Names:
  • Rituximab
  • Treatment includes the following options:
  • ACEi/ARB alone
  • ACEi/ARB + corticosteroids
  • ACEi/ARB + MMF
  • ACEi/ARB + SGLT2i
  • ACEi/ARB + MMF + corticosteroids
  • ACEi/ARB + cyclophosphamide
  • Corticosteroids alone
  • MMF alone
  • Cyclophosphamide alone
  • Corticosteroids + MMF
  • Anticomplement therapy
  • Other immunosuppressants

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number and proportion of patients with overall (complete + partial) remission following the standard therapy in Russia
Time Frame: 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).
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number and proportion of patients with complete remission
Time Frame: 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).
6 months; 12 months
Number and proportion of patients with partial remission
Time Frame: 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)
6 months; 12 months
Number and proportion of patients with relapse
Time Frame: 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
6 months; 12 months
Number and proportion of patients with progression
Time Frame: 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
6 months; 12 months
Number and proportion of patients with progression to end-stage kidney disease
Time Frame: 6 months; 12 months
Number and proportion of patients with progression to end-stage kidney disease from index-date up to 12 months
6 months; 12 months
Number and proportion of died patients
Time Frame: 6 months; 12 months
Number and proportion of patients who died from index date up to 12 months
6 months; 12 months
Time to start of maintenance dialysis
Time Frame: 6 months; 12 months
Time in months from index date to start of maintenance dialysis
6 months; 12 months
Time from the diagnosis date to the start date of dialysis
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to the start date of dialysis
6 months; 12 months
Time from the start date of treatment to the start date of dialysis
Time Frame: 6 months; 12 months
Time in months from first treatment date to the start date of dialysis
6 months; 12 months
Time from the diagnosis date to transplantation
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to transplantation
6 months; 12 months
Time from the diagnosis date to the date of complete remission
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to the date of complete remission
6 months; 12 months
Time from the diagnosis date to the date of partial remission
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to the date of partial remission
6 months; 12 months
Time from the diagnosis date to the date of overall remission (complete and partial remission)
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to the date of overall remission (complete and partial remission)
6 months; 12 months
Time to progression
Time Frame: 6 months; 12 months
Time in months from the diagnosis date to progression
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%)
Time Frame: 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
6 months; 12 months
Time to 30%, 40% and 50% decline in eGFR
Time Frame: 6 months; 12 months
Time in months from index date to 30%, 40% and 50% decline in eGFR
6 months; 12 months
Number and proportion of patients with proteinuria >1 g/24 h and eGFR ≥30 mL/min per 1.73 m2
Time Frame: 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
6 months; 12 months
Number and proportion of patients with nephrotic syndrome
Time Frame: 6 months; 12 months
Number and proportion of patients with nephrotic syndrome from index date up to 12 months
6 months; 12 months
Demographic and clinical characteristics of patients with primary C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 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
Baseline
Number of patients by morphologically verified disease form in patients with primary C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 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.
Baseline
Number of patients with presence of serum complement markers, serum factor H, rare genetic variants
Time Frame: Baseline
Number of patients with presence of serum complement markers (C3, C4, CH50, C5a), serum factor H, rare genetic variants at baseline
Baseline
Number and proportion of patients stratified by treatment sequence and specific regimen of treatment
Time Frame: Baseline; 6 months; 12 months
Number and proportion of patients stratified by treatment sequence and specific regimen of treatment
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
Time Frame: 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
Baseline; 6 months; 12 months
Number of exposed doses for non-continuous treatments (e.g., pulse therapy, rituximab infusion) in each cohort
Time Frame: Baseline; 6 months; 12 months
Number of exposed doses for non-continuous treatments (e.g., pulse therapy, rituximab infusion) in each cohort
Baseline; 6 months; 12 months
Number of patients by qualitative, semi-quantitative and quantitative scores of active and chronic lesions
Time Frame: 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
Baseline
Number of patients with signs of thrombotic microangiopathy in the biopsy specimen
Time Frame: Baseline
Number of patients with signs of thrombotic microangiopathy in the biopsy specimen at baseline
Baseline
Number of patients with acute tubular necrosis
Time Frame: Baseline
Number of patients with acute tubular necrosis at baseline
Baseline
Number of patients with presence of C1q, IgA, IgM, IgG, C3, kappa chain, lambda chain deposits
Time Frame: Baseline
Number of patients with presence of C1q, IgA, IgM, IgG, C3, kappa chain, lambda chain deposits at baseline
Baseline
Patient-reported outcomes for C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 12 months
  1. Descriptive adherence data based on question score
  2. Patient-reported outcomes, SF-36 (RAND)
12 months
Number of patients (%) with adverse events/serious adverse events by treatment option
Time Frame: 12 months
Number of patients (%) with adverse events/serious adverse events by treatment option from index date up to 12 months
12 months
Change from baseline of systolic and diastolic blood pressure (BP) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline of systolic and diastolic blood pressure (BP) (with percentiles for children) at 6 and 12 month
6 months; 12 months
Change from baseline serum creatinine level (µmol/L) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline serum creatinine level (µmol/L) at 6 and 12 months
6 months; 12 months
Change from baseline estimated glomerular filtration rate (eGFR) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline estimated glomerular filtration rate (eGFR) at 6 and 12 months
6 months; 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
Time Frame: 6 months; 12 months
Change from baseline eGFR rate of change over time (eGFR slope) at 6 and 12 months
6 months; 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
Time Frame: 6 months; 12 months
Change from baseline chronic kidney disease (CKD) stage (number of patients, %) at 6 and 12 months
6 months; 12 months
Change from baseline red blood cell count in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline red blood cell (RBC) count at 6 and 12 months
6 months; 12 months
Change from baseline RBC casts in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline RBC casts at 6 and 12 months
6 months; 12 months
Change from baseline daily proteinuria (proteinuria in g/24 hours) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline daily proteinuria (proteinuria in g/24 hours) at 6 and 12 months
6 months; 12 months
Change from baseline proteinuria >1 g/24 h in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline proteinuria >1 g/24 h at 6 and 12 months
6 months; 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
Time Frame: 6 months; 12 months
Change from baseline eGFR ≥30 mL/min per 1.73 m2 at 6 and 12 months
6 months; 12 months
Change from baseline number of patients with nephrotic syndrome (%) in patients with C3G (cohort 1), IC-MPGN (cohort 2), and overall
Time Frame: 6 months; 12 months
Change from baseline number of patients with nephrotic syndrome (%) at 6 and 12 months
6 months; 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 12, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLNP023B1RU01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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