New Analytic Tools for aHUS and C3G Diagnosis

NCT05985122 | Active Not Recruiting

• 1 other identifier: COMPRare-IRFMN
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol is part of a larger project, COMPRare (COMPlement-mediated Rare kidney diseases), which has been financed on behalf of the EJP RD (European Joint Programme on Rare Diseases) program of EU and is leaded by a scientific consortium from 7 European countries. The partners (P) of the consortium are: P1. Radboudumc Amalia Children's Hospital (The Netherlands) P2. Semmelweis University (Hungary) P3. Cordeliers Research Center (France) P4. Max Delbruck Center for Molecular Medicine (Germany) P5. Istituto di Ricerche Farmacologiche Mario Negri (Italy) P6. Lund University (Sweden) P7. Lille University (France) The general aim of the project is to define new diagnostic tools for complement activation in order to improve patients stratification and follow-up, thereby affecting time and choice of treatment in patients with aHUS and C3G. Particularly, the specific objectives of the COMPRare are:

• To develop new standardized analytic assays thereby identifying specific complement prognostic biomarkers for early diagnosis, classification, improved monitoring and treatment of patients with aHUS and C3G;
• To in-depth characterize patients' complement abnormalities in blood, in patient-derived cells and in kidney biopsies;
• To identify strategies to classify VUS/LPV
• To find new pathophysiological pathways involved in aHUS and C3G for further improving disease diagnosis, monitoring and treatment. The results of these studies will form the basis of personalized treatment with existing and upcoming complement inhibitory drugs for these rare complement-mediated kidney diseases.

Conditions

Hemolytic-Uremic Syndrome; Membranoproliferative Glomerulonephritis; Healthy

Keywords

Complement-mediated kidney diseases; Blood and tissue biomarkers; Assay standardization; Glycocalyx; Characterization of variants of unknown significance

Outcome Measures

Primary Outcomes (1)

• Determination of assay sensitivity and specificity

  We estimate that 38 VUS/LPV carrying pedigrees should be enough to demonstrate the sensitivity and specificity of the assay for classifying VUS/LPV.

  At day 0

Study Arms (2)

Patients

EXPERIMENTAL

Patients diagnosed with C3G (15 positive and 15 negative for C3NEF) at Centro Daccò, will be identified between those who provided consent to store their samples in the certified biobank (UNI EN ISO 9001:2015; certification n° 6121) of "Centro Daccò" (Centro di Risorse Biologiche Mario Negri - Biobanca Malattie Rare e Renali) and to share them with external laboratories.

Diagnostic Test: C3NEF assay

Healthy controls

ACTIVE COMPARATOR

Healthy donors will be identified between those who provided consent to store their samples in the certified biobank (UNI EN ISO 9001:2015; certification n° 6121) of "Centro Daccò" (Centro di Risorse Biologiche Mario Negri - Biobanca Malattie Rare e Renali). Subject that meet the inclusion/exclusion criteria and for which there is no enough material stored in our biobank, will be recontacted by the investigators of "Centro Daccò" and, if agree, will be asked for serum sampling after informed consent signature.

Diagnostic Test: C3NEF assay

Interventions

C3NEF assay DIAGNOSTIC_TEST

This assay will consist of a dual test, detecting C3 convertase binding C3NEF autoantibodies and measuring the functional consequence by complement alternative pathway (AP) activity using two distinct ELISA designs: C3NEF detection assay and AP activity assay.

Healthy controls; Patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients (children and adults) with C3G diagnosis
• Biobank written informed consent
• Male and female patients (children and adults) with aHUS diagnosis in acute phase (before any treatment), or in remission either untreated or undergoing anti-C5 treatment at standard dosing

You may not qualify if:

• Stx-associated HUS
• TTP (ADAMTS13\<10%)
• Plasma therapy within 2 weeks from blood sampling

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

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

Ranica, BG, 24020, Italy

Location

Related Publications (8)

• Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F, Bresin E, Tripodo C, Bettoni S, Donadelli R, Valoti E, Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E, Remuzzi G. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood. 2014 Sep 11;124(11):1715-26. doi: 10.1182/blood-2014-02-558296. Epub 2014 Jul 18.

  PMID: 25037630 BACKGROUND

• Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, Bresin E, Gamba S, Alberti M, Breno M, Perna A, Bettoni S, Sabadini E, Murer L, Vivarelli M, Noris M, Remuzzi G; Registry of Membranoproliferative Glomerulonephritis/C3 Glomerulopathy; Nastasi. Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN. J Am Soc Nephrol. 2018 Jan;29(1):283-294. doi: 10.1681/ASN.2017030258. Epub 2017 Oct 13.

  PMID: 29030465 BACKGROUND

• Donadelli R, Pulieri P, Piras R, Iatropoulos P, Valoti E, Benigni A, Remuzzi G, Noris M. Unraveling the Molecular Mechanisms Underlying Complement Dysregulation by Nephritic Factors in C3G and IC-MPGN. Front Immunol. 2018 Oct 15;9:2329. doi: 10.3389/fimmu.2018.02329. eCollection 2018.

  PMID: 30487789 BACKGROUND

• Galbusera M, Noris M, Gastoldi S, Bresin E, Mele C, Breno M, Cuccarolo P, Alberti M, Valoti E, Piras R, Donadelli R, Vivarelli M, Murer L, Pecoraro C, Ferrari E, Perna A, Benigni A, Portalupi V, Remuzzi G. An Ex Vivo Test of Complement Activation on Endothelium for Individualized Eculizumab Therapy in Hemolytic Uremic Syndrome. Am J Kidney Dis. 2019 Jul;74(1):56-72. doi: 10.1053/j.ajkd.2018.11.012. Epub 2019 Mar 7.

  PMID: 30851964 BACKGROUND

• Piras R, Breno M, Valoti E, Alberti M, Iatropoulos P, Mele C, Bresin E, Donadelli R, Cuccarolo P, Smith RJH, Benigni A, Remuzzi G, Noris M. CFH and CFHR Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis. Front Genet. 2021 Jun 11;12:670727. doi: 10.3389/fgene.2021.670727. eCollection 2021.

  PMID: 34211499 BACKGROUND

• Aiello S, Gastoldi S, Galbusera M, Ruggenenti P, Portalupi V, Rota S, Rubis N, Liguori L, Conti S, Tironi M, Gamba S, Santarsiero D, Benigni A, Remuzzi G, Noris M. C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19. Blood Adv. 2022 Jan 8;6(3):866-881. doi: 10.1182/bloodadvances.2021005246.

  PMID: 34852172 BACKGROUND

• Piras R, Valoti E, Alberti M, Bresin E, Mele C, Breno M, Liguori L, Donadelli R, Rigoldi M, Benigni A, Remuzzi G, Noris M. CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome. Front Immunol. 2023 Jan 30;13:1011580. doi: 10.3389/fimmu.2022.1011580. eCollection 2022.

  PMID: 36793547 BACKGROUND

• Gastoldi S, Aiello S, Galbusera M, Breno M, Alberti M, Bresin E, Mele C, Piras R, Liguori L, Santarsiero D, Benigni A, Remuzzi G, Noris M. An ex vivo test to investigate genetic factors conferring susceptibility to atypical haemolytic uremic syndrome. Front Immunol. 2023 Feb 9;14:1112257. doi: 10.3389/fimmu.2023.1112257. eCollection 2023.

  PMID: 36845135 BACKGROUND

MeSH Terms

Conditions

Hemolytic-Uremic Syndrome; Glomerulonephritis, Membranoproliferative

Condition Hierarchy (Ancestors)

Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Glomerulonephritis; Nephritis; Immune System Diseases

Study Officials

• Marina Noris, PhD

  Istituto Di Ricerche Farmacologiche Mario Negri

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The samples (healthy volunteers and HUS or MPGN patients) for the study will be identified between those of patients and healthy controls who provided consent to store their samples in the certified biobank of "Centro Daccò" (Centro di Risorse Biologiche Mario Negri - Biobanca Malattie Rare e Renali) for two previousely approved studies.

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 14, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)