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

NCT03723512 | Completed

• 1 other identifier: Subproject MRI ACH471-205
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Non-contrast enhanced MRI; Diffusivity; Renal microstructure; Renal function; C3G; IC-MPGN

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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.

Study Arms (1)

Whole group

EXPERIMENTAL

Whole group

Device: Non contrast-enhanced magnetic resonance imaging

Interventions

Non contrast-enhanced magnetic resonance imaging DEVICE

Non contrast-enhanced magnetic resonance imaging

Whole group

Eligibility Criteria

• Age: 17 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of C3G or IC-MPGN;
• Patients enrolled in the ACH471-205 study at the Bergamo center;
• No contraindications to perform MRI.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò

Ranica, BG, 24020, Italy

Location

Related Publications (3)

• Selby NM, Blankestijn PJ, Boor P, Combe C, Eckardt KU, Eikefjord E, Garcia-Fernandez N, Golay X, Gordon I, Grenier N, Hockings PD, Jensen JD, Joles JA, Kalra PA, Kramer BK, Mark PB, Mendichovszky IA, Nikolic O, Odudu A, Ong ACM, Ortiz A, Pruijm M, Remuzzi G, Rorvik J, de Seigneux S, Simms RJ, Slatinska J, Summers P, Taal MW, Thoeny HC, Vallee JP, Wolf M, Caroli A, Sourbron S. Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA. Nephrol Dial Transplant. 2018 Sep 1;33(suppl_2):ii4-ii14. doi: 10.1093/ndt/gfy152.

  PMID: 30137584 BACKGROUND

• Caroli A, Schneider M, Friedli I, Ljimani A, De Seigneux S, Boor P, Gullapudi L, Kazmi I, Mendichovszky IA, Notohamiprodjo M, Selby NM, Thoeny HC, Grenier N, Vallee JP. Diffusion-weighted magnetic resonance imaging to assess diffuse renal pathology: a systematic review and statement paper. Nephrol Dial Transplant. 2018 Sep 1;33(suppl_2):ii29-ii40. doi: 10.1093/ndt/gfy163.

  PMID: 30137580 BACKGROUND

• Villa G, Daina E, Brambilla P, Gamba S, Leone VF, Carrara C, Rizzo P, Noris M, Remuzzi G, Remuzzi A, Caroli A. Functional Magnetic Resonance Imaging to Monitor Disease Progression: A Prospective Study in Patients with Primary Membranoproliferative Glomerulonephritis. Nephron. 2024;148(6):367-378. doi: 10.1159/000534893. Epub 2023 Nov 3.

  PMID: 37926085 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 29, 2018
• Study Start: December 6, 2018
• Primary Completion: February 17, 2021
• Study Completion: February 17, 2021
• Last Updated: November 26, 2021

Record last verified: 2021-11

Locations

IT (1)