Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

NCT ID: NCT05067127

Last Updated: 2026-01-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-12

Study Completion Date

2025-01-14

Brief Summary

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This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.

Detailed Description

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Conditions

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C3G IC-MPGN C3 Glomerulopathy C3 Glomerulonephritis Complement 3 Glomerulopathy Complement 3 Glomerulopathy (C3G) Complement 3 Glomerulonephritis Dense Deposit Disease DDD Membranoproliferative Glomerulonephritis Membranoproliferative Glomerulonephritis (MPGN) Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Group 1: Pegcetacoplan administration

Subcutaneous infusion of 20mL (1080 mg), twice weekly (for adults or adolescents \>50kg), and the three other weight-based doses either of 10mL (540mg), 12mL (648mg), or 15mL (810mg)

Group Type EXPERIMENTAL

Pegcetacoplan

Intervention Type DRUG

Complement (C3) Inhibitor

Group 2: Placebo administration

Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Sterile solution of equal volume to active arm

Interventions

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Pegcetacoplan

Complement (C3) Inhibitor

Intervention Type DRUG

Placebo

Sterile solution of equal volume to active arm

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
2. A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).
3. Evidence of active renal disease, based on one or more of the following:

1. In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2+ C3c staining on the baseline renal biopsy.
2. In adolescents not providing a baseline renal biopsy, at least one of the following:

* Plasma sC5b-9 level above the upper limit of normal during screening
* Serum C3 below the LLN during screening
* Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysis of urine.
* Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history.
4. No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
5. At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.
6. eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.
7. Stable regimen for C3G/IC-MPGN treatment, as described below:

1. Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization
2. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 12 weeks prior to the baseline renal biopsy and randomization.
3. If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.
8. Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.

Exclusion Criteria

1. Previous exposure to pegcetacoplan.
2. C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.
3. Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.
4. Body weight greater than 100 kg at screening.
5. Hypersensitivity to pegcetacoplan or to any of the excipients.
6. History of meningococcal disease.
7. Malignancy, except for the following:

1. Cured basal or squamous cell skin cancer
2. Curatively treated in situ disease
3. Malignancy-free and off treatment for ≥5 years
8. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
9. An absolute neutrophil count \<1000 cells/mm3 at screening.
10. Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.
11. Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug.
12. Presence or suspicion of severe infection during the screening period (including but not limited to recurrent or chronic infections) that, in the opinion of the investigator, may place the participant at unacceptable risk by study participation.
13. Known or suspected hereditary fructose intolerance.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Apellis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Academic Medical Research Institute

Los Angeles, California, United States

Site Status

Keck School of Medicine, University of Southern California

Los Angeles, California, United States

Site Status

Ronald Reagan UCLA Medical Center (01035)

Los Angeles, California, United States

Site Status

UCI Center for Clinical Research

Orange, California, United States

Site Status

UC Davis Medical Center (Transplant Research) (01016)

Sacramento, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Fides Clinical Research, LLC (01042)

Atlanta, Georgia, United States

Site Status

Institute for Public Health and Medicine Northwestern University Northwestern University (01041)

Chicago, Illinois, United States

Site Status

NANIU Research Chicago (01040)

Oak Brook, Illinois, United States

Site Status

Nephrology Associates of Northern IL and Inn (01043)

Fort Wayne, Indiana, United States

Site Status

The University of Iowa

Iowa City, Iowa, United States

Site Status

Boston Children's Hospital (01013)

Boston, Massachusetts, United States

Site Status

Renal and Transplant Associates of New England, PC

Springfield, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Hackensack Meridian Health

Hackensack, New Jersey, United States

Site Status

Cohen Children Hospital

New Hyde Park, New York, United States

Site Status

CUIMC - Columbia Nephrology

New York, New York, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health & Science University (01038)

Portland, Oregon, United States

Site Status

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, United States

Site Status

MedResearch Inc

El Paso, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Hospital Universitario Austral

Buenos Aires, , Argentina

Site Status

Hospital Privado-Universitario de Cordoba

Córdoba, , Argentina

Site Status

Clinica Privada Velez Sarsfield

Córdoba, , Argentina

Site Status

Canberra Hospital - Renal Clinical Trials & Research Unit

Garran, Australian Capital Territory, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Monash University

Box Hill, , Australia

Site Status

St. Vincents Melbourne

Fitzroy, , Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

Medical University Hospital Innsbruck (43004)

Innsbruck, , Austria

Site Status

Medizinische Universität Wien

Vienna, , Austria

Site Status

Hopital Erasme HUB Service Pharmacie

Brussels, , Belgium

Site Status

University Hospital Antwerp (32004)

Edegem, , Belgium

Site Status

Catholic University of Leuven

Leuven, , Belgium

Site Status

CHU Sart-Tilman

Liège, , Belgium

Site Status

Clinical Trials CHU de Liège

Liège, , Belgium

Site Status

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Site Status

Centro de Tratamento de Doencas Renais

Juiz de Fora, Minas Gerais, Brazil

Site Status

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

HC UNESP Botucatu

Botucatu, , Brazil

Site Status

Hospital Universitario Walter Cantidio

Fortaleza, , Brazil

Site Status

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Site Status

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Site Status

Real Hospital Portuguas de Beneficancia em Pernambuco

Recife, , Brazil

Site Status

Hospital das Clinicas de Ribeirao Preto, Division of Nephrology

Ribeirão Preto, , Brazil

Site Status

Nefrologia I-Dor

Rio de Janeiro, , Brazil

Site Status

Ruschel Medicina E Pesquisa Clinica

Rio de Janeiro, , Brazil

Site Status

Hospital de Base

São José do Rio Preto, , Brazil

Site Status

UNIFESP - Hospital Sao Paulo

São Paulo, , Brazil

Site Status

Instituto da Crianca-Hospital das Clinicas University of Sao Paulo

São Paulo, , Brazil

Site Status

HCFMUSP-Hospital Clinicas da Faculdade Medicina da Universidade de São Paulo

São Paulo, , Brazil

Site Status

Hospital for Sick Children (11003)

Toronto, Ontario, Canada

Site Status

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

Institute for Clinical and Experimental Medicine

Prague, , Czechia

Site Status

Faculty Hospital Kralovske Vinohrady (42002)

Prague, , Czechia

Site Status

CHU de Bordeaux - Hopital Pellegrin

Bordeaux, , France

Site Status

Hopital Henri-Mondor

Créteil, , France

Site Status

Hospital Edouard Herriot, Hospices Civils de Lyon

Lyon, , France

Site Status

CHU Montpellier, Hopital Lapeyronie

Montpellier, , France

Site Status

Nantes University Hospital

Nantes, , France

Site Status

Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology

Paris, , France

Site Status

Hopital Necker (33014)

Paris, , France

Site Status

Hôpital Européen Georges-Pompidou

Paris, , France

Site Status

CHU de Saint Etienne, Hospital Nord

Saint-Priest-en-Jarez, , France

Site Status

University Hospital Strasbourg

Strasbourg, , France

Site Status

Rangueil Hospital-University Hospital Center (CHU) of Toulouse

Toulouse, , France

Site Status

Charite Universitatsmedizin (49007)

Berlin, , Germany

Site Status

Universitatsklinikum Essen (AoR), Zentrum fur Kinder (49005)

Essen, , Germany

Site Status

Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen

Hanover, , Germany

Site Status

Universitatsmedizin Mainz

Mainz, , Germany

Site Status

Universitatsklinikum Munster

Münster, , Germany

Site Status

University Hospital Regensburg (49004)

Regensburg, , Germany

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Institute of Pediatric Nephrology

Petah Tikva, , Israel

Site Status

Policlinico di Bari

Bari, , Italy

Site Status

Policlinico Sant Orsola-Malpighi

Bologna, , Italy

Site Status

IRCCS Istituto Giannina Gaslini (39012)

Genova, , Italy

Site Status

Universita degli Studi di Messina

Messina, , Italy

Site Status

Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Milan, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Azienda Ospedaliera Universitaria di Padova (39011)

Padua, , Italy

Site Status

Instituti Clinici Scientifici Maugeri SPA-IRCCS

Pavia, , Italy

Site Status

Ospedale Pediatrico Bambino Gesu

Rome, , Italy

Site Status

Nagoya University Hospital (81003)

Nagoya, Aichi-ken, Japan

Site Status

Aichi Children's Health and Medical Center

Ōbu, Aichi-ken, Japan

Site Status

Gunma University Hospital (81006)

Maebashi, Gunma, Japan

Site Status

NHO Kanazawa Medical Center

Kanazawa, Ishikawa-ken, Japan

Site Status

Nagasaki University Hospital (81005)

Nagasaki, Nagasaki, Japan

Site Status

Seirei Hamamatsu General Hospital (81004)

Hamamatsu, Shizuoka, Japan

Site Status

Kitano Hospital

Osaka, , Japan

Site Status

Kyorin University Hospital (81009)

Tokyo, , Japan

Site Status

Emma Kinderziekenhuis, Amsterdam UMC

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi

Lodz, , Poland

Site Status

SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi

Lodz, , Poland

Site Status

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status

Yonsei University College of Medicine, Sinchon Severance Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital (82005)

Seoul, , South Korea

Site Status

Seoul National University Hospital

Soeul, , South Korea

Site Status

Fundació Puigvert

Barcelona, , Spain

Site Status

Hospital Universitari Vall D'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica

Barcelona, , Spain

Site Status

Hospital Materno Infantil Sant Joan de Deu

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre, Nephrology Department

Madrid, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

University Hospital of Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario Dr Peset

Valencia, , Spain

Site Status

Inselspital, Bern University Hospital

Bern, , Switzerland

Site Status

CHUV Lausanne

Lausanne, , Switzerland

Site Status

Universitatsspital Zurich

Zurich, , Switzerland

Site Status

Gloucestershire Hospitals NHS Foundation Trust

Gloucester, , United Kingdom

Site Status

University Hospitals of Leicester NHS trust (44003)

Leicester, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust (44015)

London, , United Kingdom

Site Status

Evelina London Children Hospital (44016)

London, , United Kingdom

Site Status

St George'Äôs University Hospitals NHS Foundation Trust (44014)

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Great Ormond Street Hospital Foundation Trust

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Nottingham Children's Hospital

Nottingham, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Canada Czechia France Germany Israel Italy Japan Netherlands Poland South Korea Spain Switzerland United Kingdom

References

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Fakhouri F, Bomback AS, Ariceta G, Delmas Y, Dixon BP, Gale DP, Greenbaum LA, Han SH, Isbel N, Le Quintrec M, Licht C, Mastrangelo A, Mizuno M, Neves de Holanda MI, Pickering MC, Remuzzi G, Van De Kar N, Vivarelli M, Walker PD, Wallace D, Zecher D, Francois C, Deschatelets P, Li L, Wang Z, Abad-Franch L, Kinnman N, Lopez-Lazaro L, Szamosi J, Nester CM; VALIANT Trial Investigators Group. Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN. N Engl J Med. 2025 Dec 4;393(22):2210-2220. doi: 10.1056/NEJMoa2501510.

Reference Type DERIVED
PMID: 41337715 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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APL2-C3G-310

Identifier Type: -

Identifier Source: org_study_id

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