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

NCT05067127 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: APL2-C3G-310
• Study Type: interventional
• Target: 124
• Locations: 18 countries
• Sites: 120

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Randomized Controlled Period: Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26

  Baseline uPCR value was calculated as the average of the uPCR measurements from at least 6 of the 9 first-morning spot urine (FMU) samples collected between the start of screening and Day 1, inclusive. The uPCR values used to calculate baseline included those from the samples collected on Day -2, Day -1, and before dosing on Day 1. In situations where less than 6 samples or more than 9 samples were collected, the average of all collected samples was used for baseline derivation. The difference between treatment groups using a composite contrast of equal-weighted average over Weeks 24, 25, and 26 was estimated.

  Baseline (Day -70 to Day 1) to Week 26

Secondary Outcomes (10)

• Randomized Controlled Period: Percentage of Subjects Who Achieved the Composite Renal Endpoint at Week 26

  Week 26

• Randomized Controlled Period: Percentage of Subjects With a Reduction of At Least 50% From Baseline in Urine Protein-to-Creatinine Ratio at Week 26

  Baseline (Day -70 to Day 1) and Week 26

• Randomized Controlled Period: Change From Baseline in the C3 Glomerulopathy (C3G) Histologic Index Activity Score at Week 26

  Baseline (Day 1) and Week 26

• Randomized Controlled Period: Percentage of Subjects Who Showed Decrease in C3c Staining on Renal Biopsy From Baseline at Week 26

  Baseline (Day 1) and Week 26

• Randomized Controlled Period: Change From Baseline in Estimated Glomerular Filtration Rate at Week 26

  Baseline (Day 1) and Week 26

Study Arms (2)

Group 1: Pegcetacoplan administration

EXPERIMENTAL

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)

Drug: Pegcetacoplan

Group 2: Placebo administration

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Pegcetacoplan DRUG

Complement (C3) Inhibitor

Group 1: Pegcetacoplan administration

Placebo OTHER

Sterile solution of equal volume to active arm

Group 2: Placebo administration

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
• A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).
• Evidence of active renal disease, based on one or more of the following:
• 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.
• 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.
• No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
• 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.
• 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.
• Stable regimen for C3G/IC-MPGN treatment, as described below:
• 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
• 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.

You may not qualify if:

• Previous exposure to pegcetacoplan.
• 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.
• 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.
• Body weight greater than 100 kg at screening.
• Hypersensitivity to pegcetacoplan or to any of the excipients.
• History of meningococcal disease.
• Malignancy, except for the following:
• Cured basal or squamous cell skin cancer
• Curatively treated in situ disease
• Malignancy-free and off treatment for ≥5 years
• Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
• An absolute neutrophil count \<1000 cells/mm3 at screening.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (125)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Keck School of Medicine, University of Southern California

Los Angeles, California, 90033, United States

Location

Ronald Reagan UCLA Medical Center (01035)

Los Angeles, California, 90095, United States

Location

UCI Center for Clinical Research

Orange, California, 92868, United States

Location

UC Davis Medical Center (Transplant Research) (01016)

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Fides Clinical Research, LLC (01042)

Atlanta, Georgia, 30342, United States

Location

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

Chicago, Illinois, 60611, United States

Location

NANIU Research Chicago (01040)

Oak Brook, Illinois, 60523, United States

Location

Nephrology Associates of Northern IL and Inn (01043)

Fort Wayne, Indiana, 46804, United States

Location

The University of Iowa

Iowa City, Iowa, 52242, United States

Location

Boston Children's Hospital (01013)

Boston, Massachusetts, 02115, United States

Location

Renal and Transplant Associates of New England, PC

Springfield, Massachusetts, 01107, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64102, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Cohen Children Hospital

New Hyde Park, New York, 11040, United States

Location

CUIMC - Columbia Nephrology

New York, New York, 10032, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University (01038)

Portland, Oregon, 97239, United States

Location

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, 18017, United States

Location

MedResearch Inc

El Paso, Texas, 79902, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Hospital Universitario Austral

Buenos Aires, 1629, Argentina

Location

Hospital Privado-Universitario de Cordoba

Córdoba, CPA X5016KEH, Argentina

Location

Clinica Privada Velez Sarsfield

Córdoba, X5000, Argentina

Location

Canberra Hospital - Renal Clinical Trials & Research Unit

Garran, Australian Capital Territory, 2605, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, QLD 4102, Australia

Location

Monash University

Box Hill, VIC 3128, Australia

Location

St. Vincents Melbourne

Fitzroy, VIC 3065, Australia

Location

Princess Alexandra Hospital

Woolloongabba, QLD 4102, Australia

Location

Medical University Hospital Innsbruck (43004)

Innsbruck, 6020, Austria

Location

Medizinische Universität Wien

Vienna, A-1090, Austria

Location

Hopital Erasme HUB Service Pharmacie

Brussels, 1070, Belgium

Location

University Hospital Antwerp (32004)

Edegem, 2650, Belgium

Location

Catholic University of Leuven

Leuven, B-3000, Belgium

Location

CHU Sart-Tilman

Liège, B-4000, Belgium

Location

Clinical Trials CHU de Liège

Liège, B-4000, Belgium

Location

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Centro de Tratamento de Doencas Renais

Juiz de Fora, Minas Gerais, 36025-340, Brazil

Location

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

HC UNESP Botucatu

Botucatu, 18618-687, Brazil

Location

Hospital Universitario Walter Cantidio

Fortaleza, 60430-372, Brazil

Location

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90020-090, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Real Hospital Portuguas de Beneficancia em Pernambuco

Recife, 52010-095, Brazil

Location

Hospital das Clinicas de Ribeirao Preto, Division of Nephrology

Ribeirão Preto, 14110-000, Brazil

Location

Nefrologia I-Dor

Rio de Janeiro, 22211-225, Brazil

Location

Ruschel Medicina E Pesquisa Clinica

Rio de Janeiro, 22270-060, Brazil

Location

Hospital de Base

São José do Rio Preto, 150900-000, Brazil

Location

UNIFESP - Hospital Sao Paulo

São Paulo, 04038-002, Brazil

Location

Instituto da Crianca-Hospital das Clinicas University of Sao Paulo

São Paulo, 05403-000, Brazil

Location

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

São Paulo, 05403-900, Brazil

Location

Hospital for Sick Children (11003)

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, QC H1T2M4, Canada

Location

Institute for Clinical and Experimental Medicine

Prague, 140 21, Czechia

Location

Faculty Hospital Kralovske Vinohrady (42002)

Prague, Czechia

Location

CHU de Bordeaux - Hopital Pellegrin

Bordeaux, 33076, France

Location

Hopital Henri-Mondor

Créteil, 94010, France

Location

Hospital Edouard Herriot, Hospices Civils de Lyon

Lyon, 69437, France

Location

CHU Montpellier, Hopital Lapeyronie

Montpellier, 34295, France

Location

Nantes University Hospital

Nantes, 44093, France

Location

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

Paris, 59037, France

Location

Hopital Necker (33014)

Paris, 75015, France

Location

Hôpital Européen Georges-Pompidou

Paris, 75015, France

Location

CHU de Saint Etienne, Hospital Nord

Saint-Priest-en-Jarez, 42055, France

Location

University Hospital Strasbourg

Strasbourg, 67091, France

Location

Rangueil Hospital-University Hospital Center (CHU) of Toulouse

Toulouse, 31059, France

Location

Charite Universitatsmedizin (49007)

Berlin, 10117, Germany

Location

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

Essen, D-45147, Germany

Location

Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen

Hanover, 30625, Germany

Location

Universitatsmedizin Mainz

Mainz, 55131, Germany

Location

Universitatsklinikum Munster

Münster, 48149, Germany

Location

University Hospital Regensburg (49004)

Regensburg, 93053, Germany

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Institute of Pediatric Nephrology

Petah Tikva, 4920235, Israel

Location

Policlinico di Bari

Bari, 70123, Italy

Location

Policlinico Sant Orsola-Malpighi

Bologna, 40138, Italy

Location

IRCCS Istituto Giannina Gaslini (39012)

Genova, 16147, Italy

Location

Universita degli Studi di Messina

Messina, 98125, Italy

Location

Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Milan, 20156, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera Universitaria di Padova (39011)

Padua, 35128, Italy

Location

Instituti Clinici Scientifici Maugeri SPA-IRCCS

Pavia, 27100, Italy

Location

Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

Location

Nagoya University Hospital (81003)

Nagoya, Aichi-ken, 466-8560, Japan

Location

Aichi Children's Health and Medical Center

Ōbu, Aichi-ken, 474-8710, Japan

Location

Gunma University Hospital (81006)

Maebashi, Gunma, 371-8511, Japan

Location

NHO Kanazawa Medical Center

Kanazawa, Ishikawa-ken, 9208650, Japan

Location

Nagasaki University Hospital (81005)

Nagasaki, Nagasaki, 852-8501, Japan

Location

Seirei Hamamatsu General Hospital (81004)

Hamamatsu, Shizuoka, 430-8558, Japan

Location

Kitano Hospital

Osaka, 530-8480, Japan

Location

Kyorin University Hospital (81009)

Tokyo, 181-8611, Japan

Location

Emma Kinderziekenhuis, Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Radboud University Medical Center

Nijmegen, 6500 HB, Netherlands

Location

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

Lodz, 90-153, Poland

Location

SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi

Lodz, 92-213, Poland

Location

Keimyung University Dongsan Medical Center

Daegu, 42601, South Korea

Location

Yonsei University College of Medicine, Sinchon Severance Hospital

Seoul, 03722, South Korea

Location

Seoul National University Hospital (82005)

Seoul, 3080, South Korea

Location

Seoul National University Hospital

Soeul, 03080, South Korea

Location

Fundació Puigvert

Barcelona, 08025, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

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

Barcelona, 08035, Spain

Location

Hospital Materno Infantil Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitario 12 de Octubre, Nephrology Department

Madrid, 28041, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

University Hospital of Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario Dr Peset

Valencia, 46017, Spain

Location

Inselspital, Bern University Hospital

Bern, CH-3010, Switzerland

Location

CHUV Lausanne

Lausanne, CH-1011, Switzerland

Location

Universitatsspital Zurich

Zurich, CH-8091, Switzerland

Location

Gloucestershire Hospitals NHS Foundation Trust

Gloucester, GL1 3NN, United Kingdom

Location

University Hospitals of Leicester NHS trust (44003)

Leicester, LE1 5WW, United Kingdom

Location

Royal Free London NHS Foundation Trust (44015)

London, NW3 2QG, United Kingdom

Location

Evelina London Children Hospital (44016)

London, SE1 7EH, United Kingdom

Location

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

London, SW17 0QT, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Great Ormond Street Hospital Foundation Trust

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Nottingham Children's Hospital

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41337715 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Interventions

pegcetacoplan

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

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 5, 2021
• Study Start: November 12, 2021
• Primary Completion: June 26, 2024
• Study Completion: January 14, 2025
• Last Updated: January 29, 2026
• Results First Posted: August 6, 2025

Record last verified: 2025-08

Locations

CZ (2); DE (6); BE (5); AU (2); NL (3); JP (8); CA (2); CH (3); US (26); GB (9); KR (4); PL (2); ES (8); IT (9); IL (2); BR (15); AR (3); FR (11)