Non-contrast Enhanced MRI in Patients With C3 Glomerulopathy (C3G) or Immune-complex Membranoproliferative Glomerulonephritis (IC-MPGN) Enrolled in the ACH471-205 Study

Study Overview
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Brief Summary
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Functional and quantitative renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. However, there are knowledge gaps that must be addressed before renal MRI methods could be more widely adopted in clinical research and ultimately be transferred to clinical practice, including the biological basis of different MRI biomarkers, and how the application of these biomarkers will improve patient care. Among renal MRI techniques, renal diffusion weighted MRI (DWI) has been increasingly used in the last decade, showing high potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease (CKD), as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. Within the ready-to-start ACH471-205 clinical trial, an Open-Label Phase 2 Proof-of-Concept Study in Patients with C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) treated with ACH-0144471, aimed at evaluating the efficacy of 12 months of oral ACH-0144471 in patients with C3G or IC-MPGN, patients will undergo baseline and 12-month follow-up renal biopsies, and renal function will be assessed over time by estimated or measured (when available) glomerular filtration rate (GFR). Adding multi-parametric NCE-MRI to the examinations under the ACH471-205 study protocol will give the opportunity to elucidate, in a well-defined cohort of patients, the potential of NCE-MRI as biomarker of renal microstructure and functional change.

Official Title
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Sub-project of the Clinical Protocol ACH471-205 An Open-Label Phase 2 Proof-of-Concept Study in Patients With C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) Treated With ACH-0144471

Conditions
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C3 Glomerulonephritis, C3 Glomerulopathy, Immune Complex Membranoproliferative Glomerulonephritis, IC-MPGN, Dense Deposit Disease

Intervention / Treatment
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* Device: Non contrast-enhanced magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of C3G or IC-MPGN; Patients enrolled in the ACH471-205 study at the Bergamo center; No contraindications to perform MRI. Exclusion Criteria: - Ferro-magnetic prosthesis, aneurysm clips, severe claustrophobia or other contraindications or exclusions interfering with the MRI assessment.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole group<br>Whole group | Device: Non contrast-enhanced magnetic resonance imaging<br>* Non contrast-enhanced magnetic resonance imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median diffusivity (D) in the kidney, renal cortex and medulla. |  | At baseline (prior to baseline biopsy). | 
| Median diffusivity (D) in the kidney, renal cortex and medulla. |  | At 12 months (prior to follow-up biopsy). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal artery blood flow and renal plasma flow. |  | At baseline (prior to baseline biopsy). | 
| Renal artery blood flow and renal plasma flow. |  | At 12 months (prior to follow-up biopsy). | 
| Change in median diffusivity in the kidney, renal cortex and medulla after 12-month treatment with ACH-0144471. |  | At 12 months follow-up. | 
| Change in renal artery blood flow and renal plasma flow after 12-month treatment with ACH-0144471. |  | At 12 months follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-contrast enhanced MRI, Diffusivity, Renal microstructure, Renal function, C3G, IC-MPGN