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European Union · Phase II and III, including IIIb · C3 glomerulopathy

EU Phase II and III C3 glomerulopathy trials: sites, PIs and sample sizes

Mario Negri Institute in Ranica and Radboud University Medical Center each appear in five of seven studies involving patients with C3 glomerulopathy (C3G). Across the seven studies, 68 EU sites and 76 named investigators span 13 countries, with separate networks for Phase II development, pivotal trials and long-term follow-up.

7studies
three Phase II, four Phase III/IIIb
68listed EU sites
across 13 countries
76named principal investigators
across all seven studies

Top 10 sites · All seven studies

Four centres span both pivotal trials and their extensions

Mario Negri, Radboud, Bambino Gesù and Milan Policlinico all appear in VALIANT, APPEAR-C3G and both extension studies. Mario Negri and Radboud also participate in NOBLE’s post-transplant study.

EU sites by distinct studies involving C3G
Mario Negri Institute, RanicaRanica · Italy5
Radboud University Medical CenterNijmegen · Netherlands5
Bambino Gesù Children’s HospitalRome · Italy4
Milan PoliclinicoMilan · Italy4
12 de Octubre University HospitalMadrid · Spain3
Vall d’Hebron University HospitalBarcelona · Spain3
Amsterdam UMC, AMC campusAmsterdam · Netherlands2
Georges-Pompidou European HospitalParis · France2
Hannover Medical SchoolHanover · Germany2
Hospital Universitario Virgen De La MacarenaSevilla · Spain2

Differences by phase and patient population

Phase IIThree distinct networksThe three studies list 19 sites with no site shared between them. NOBLE lists three centres, OMS906-C3G-001 three, and the Swedish Reninblock-C3G study 13.

C3G onlyAPPEAR-C3G and Reninblock-C3GThe two studies together list 33 sites, with no shared site. The other five studies also admit IC-MPGN or idiopathic ICGN, so their site experience covers mixed populations.

ExtensionsTwo returning-patient studiesThe extensions list 45 sites, six shared between them. Their additional appearances represent follow-up experience, rather than independent newly recruited patient populations.

Site counts group departments and naming variants at the same centre. Separately identifiable hospital campuses remain distinct. Counts include historical and currently listed participation, not recruitment performance or open-site availability.

Top 10 principal investigators · All seven studies

Giuseppe Remuzzi appears in five studies, Marina Vivarelli in four

Four investigators follow with three study appearances each. Shared institutions can involve different adult, paediatric or transplant investigators.

Principal investigators by distinct studies involving C3G
Giuseppe RemuzziItaly5
Marina VivarelliItaly4
Gema Ariceta IraolaSpain3
Giovanni MontiniItaly3
Raphael DuivenvoordenNetherlands3
Teresa Cavero EscribanoSpain3
Aiko De VriesNetherlands2
Aude ServaisFrance2
Bernhard BanasGermany2
Christian PatryGermany2

Differences by phase and patient population

Pivotal Phase IIIVALIANT and APPEAR-C3GGiuseppe Remuzzi and Marina Vivarelli appear in both. At Milan Policlinico, VALIANT names Giovanni Montini while APPEAR-C3G names Gianluigi Ardissino.

Post-transplantNOBLE · Phase IIThe three named investigators are Gere Sunder-Plassmann, Raphaël Duivenvoorden and Giuseppe Remuzzi. NOBLE specifically studies recurrent disease in kidney transplants.

C3G onlyAdult and paediatric settingsAPPEAR-C3G names 20 investigators and Reninblock-C3G names 17, with no investigator shared between the two studies. Their patient age ranges and treatment settings differ.

Top 10 of 13 EU countries

Italy and the Netherlands each appear in five studies

Germany follows with four. Italy, the Netherlands and Germany are the only countries appearing in both pivotal Phase III trials and both extensions.

EU countries by distinct studies involving C3G
Italy5
Netherlands5
Germany4
Austria3
France3
Spain3
Czechia2
Greece2
Belgium1
Lithuania1

Poland, Slovakia and Sweden also appear in one study each. Countries tied on study count are ordered alphabetically. A multinational study can appear in several countries.

Differences by phase and patient population

Phase IISix EU countriesNOBLE lists Austria, Italy and the Netherlands. OMS906-C3G-001 lists Lithuania and Poland. Reninblock-C3G is confined to Sweden in the EU records.

C3G onlyEight-country networkAPPEAR-C3G lists France, Germany, Greece, Italy, the Netherlands, Slovakia and Spain. Reninblock-C3G adds Sweden, with 13 listed centres.

ExtensionsNine EU countriesThe two extensions share Czechia, France, Germany, Italy, the Netherlands and Spain. The iptacopan extension additionally lists Greece, while VALE additionally lists Austria and Belgium.

Worldwide participants · Actual and estimated enrollment

VALIANT enrolled 124 participants, while the largest extension targets 225

NOBLE enrolled 13 participants. The other five figures are registry estimates, including 98 for APPEAR-C3G and 100 for VALE.

Worldwide study enrollment · actual or estimated
Iptacopan extensionPhase IIIb · estimated · mixed C3G/IC-MPGN225
VALIANTPhase III · actual · mixed C3G/IC-MPGN124
VALEPhase III · estimated · mixed C3G/IC-MPGN100
APPEAR-C3GPhase III · estimated · C3G only98
Reninblock-C3GPhase II · estimated · C3G only30
OMS906-C3G-001Phase II · estimated · mixed C3G/ICGN20
NOBLEPhase II · actual · post-transplant C3G/IC-MPGN13

Blue bars: actual enrollment. Green bars: estimated enrollment. Mixed-disease totals include patients with conditions other than C3G.

Differences by phase and patient population

C3G onlyPhase III and Phase IIAPPEAR-C3G lists an estimate of 98, including its adolescent cohort. Reninblock-C3G plans 30 children and adults.

Mixed populationsC3G and related glomerular diseaseVALIANT’s 124 actual participants and NOBLE’s 13 include C3G or IC-MPGN. OMS906-C3G-001 plans 20 participants with C3G or idiopathic ICGN. These are not C3G-only counts.

ExtensionsReturning participantsThe iptacopan extension estimates 225 across eligible parent studies and VALE estimates 100 VALIANT completers. Participants can occur in both a parent trial and its extension, so study totals must not be added as unique patients.

Enrollment figures use each linked ClinicalTrials.gov record’s latest posted value as retrieved on 17 September 2026. An estimated figure is a target, not confirmed enrollment. Country and site rankings use the listed EU trial locations.

The seven EU Phase II and III C3G studies

Five are parent or standalone studies, and two continue treatment after a parent study. IC-MPGN means immune-complex membranoproliferative glomerulonephritis. ICGN means immune complex-mediated glomerulonephritis.

Study / EU CT numberPhaseTreatment and patient populationEU sites
VALIANT
2024-514130-20-00
IIIPegcetacoplan, randomized placebo-controlled. C3G or IC-MPGN, native kidneys or post-transplant recurrence.12
APPEAR-C3G
2023-509331-83-00
IIIIptacopan, randomized placebo-controlled. C3G, adult and adolescent cohorts.20
Iptacopan extension
2023-509343-27-00
IIIbOpen-label follow-up after parent studies. C3G or idiopathic IC-MPGN.33
VALE
2023-504625-39-00
IIIPegcetacoplan extension for VALIANT completers with clinical benefit. C3G or IC-MPGN.18
NOBLE
2024-511544-36-00
IIPegcetacoplan, randomized open-label. Adults with post-transplant recurrence of C3G or IC-MPGN.3
OMS906-C3G-001
2023-508669-33-00
IIOMS906, open-label proof of concept. Adults with C3G, including dense deposit disease, or idiopathic ICGN.3
Reninblock-C3G
2024-515892-36-00
IIAliskiren versus enalapril, randomized crossover. C3G in children aged ≥6 years and adults.13

The iptacopan extension is described as Phase IIIb in CTIS, with an integrated III/IV phase code, and as Phase III in ClinicalTrials.gov. It is included in the Phase III group. Study listings do not establish that a site is currently recruiting.

Sources: CTIS trial records and protocols and the seven ClinicalTrials.gov records linked above, reviewed 17 September 2026. Rankings count distinct study protocols, including extensions. The charts show up to ten entries, with alphabetical ordering for ties. Site and investigator appearances describe the whole study, not confirmed C3G enrollment at each site.

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