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

A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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)
• Intervention / Treatment: Drug: Pegcetacoplan; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Apellis Clinical Trial Information Line; Phone Number: 833-284-6361 (833-CTinfo1); Email: clinicaltrials@apellis.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1629
    • Hospital Universitario Austral
  • Córdoba, Argentina, CPA X5016KEH
    • Hospital Privado-Universitario de Cordoba
  • Córdoba, Argentina, X5000
    • Clínica Privada Velez Sarsfield
• Australia
  • Box Hill, Australia, VIC 3128
    • Monash University
  • Fitzroy, Australia, VIC 3065
    • St. Vincents Melbourne
  • Woolloongabba, Australia, QLD 4102
    • Princess Alexandra Hospital
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital - Renal Clinical Trials & Research Unit
  • Queensland
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Princess Alexandra Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Medical University Hospital Innsbruck (43004)
  • Wien, Austria, A-1090
    • Medizinische Universität Wien
• Belgium
  • Bruxelles, Belgium, 1070
    • Hopital Erasme HUB Service Pharmacie
  • Edegem, Belgium, 2650
    • University Hospital Antwerp (32004)
  • Leuven, Belgium, B-3000
    • Catholic University of Leuven
  • Liège, Belgium, B-4000
    • CHU Sart-Tilman
  • Liège, Belgium, B-4000
    • Clinical Trials CHU de Liège
• Brazil
  • Botucatu, Brazil, 18618-687
    • HC UNESP Botucatu
  • Fortaleza, Brazil, 60430-372
    • Hospital Universitario Walter Cantidio
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clinicas de Porto Alegre
  • Porto Alegre, Brazil, 90020-090
    • Irmandade da Santa Casa de Misericórdia de Porto Alegre
  • Recife, Brazil, 52010-095
    • Real Hospital Portuguas de Beneficancia em Pernambuco
  • Ribeirão Preto, Brazil, 14110-000
    • Hospital das Clinicas de Ribeirao Preto, Division of Nephrology
  • Rio De Janeiro, Brazil, 22270-060
    • Ruschel Medicina e Pesquisa Clínica
  • Rio De Janeiro, Brazil, 22211-225
    • Nefrologia I-Dor
  • São José Do Rio Preto, Brazil, 150900-000
    • Hospital de Base
  • São Paulo, Brazil, 04038-002
    • UNIFESP - Hospital Sao Paulo
  • São Paulo, Brazil, 05403-000
    • Instituto da Crianca-Hospital das Clinicas University of Sao Paulo
  • São Paulo, Brazil, 05403-900
    • HCFMUSP-Hospital Clinicas da Faculdade Medicina da Universidade de São Paulo
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericórdia de Belo Horizonte
    • Juiz De Fora, Minas Gerais, Brazil, 36025-340
      • Centro de Tratamento de Doencas Renais
  • RS
    • Porto Alegre, RS, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children (11003)
  • Quebec
    • Montréal, Quebec, Canada, QC H1T2M4
      • Hôpital Maisonneuve-Rosemont
• Czechia
  • Prague, Czechia, 140 21
    • Institute for Clinical and Experimental Medicine
  • Prague, Czechia
    • Faculty Hospital Kralovske Vinohrady (42002)
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux - Hôpital Pellegrin
  • Créteil, France, 94010
    • Hopital Henri-Mondor
  • Lyon, France, 69437
    • Hospital Edouard Herriot, Hospices Civils de Lyon
  • Montpellier, France, 34295
    • CHU Montpellier, Hopital Lapeyronie
  • Nantes, France, 44093
    • Nantes university hospital
  • Paris, France, 75015
    • Hopital Europeen Georges-Pompidou
  • Paris, France, 59037
    • Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology
  • Paris, France, 75015
    • Hopital Necker (33014)
  • Saint-Priest-en-Jarez, France, 42055
    • CHU de Saint Etienne, Hospital Nord
  • Strasbourg, France, 67091
    • University Hospital Strasbourg
  • Toulouse, France, 31059
    • Rangueil Hospital-University Hospital Center (CHU) of Toulouse
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin (49007)
  • Essen, Germany, D-45147
    • Universitatsklinikum Essen (AoR), Zentrum fur Kinder (49005)
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Regensburg, Germany, 93053
    • University Hospital Regensburg (49004)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Petah Tikva, Israel, 4920235
    • Institute of Pediatric Nephrology
• Italy
  • Bari, Italy, 70123
    • Policlinico di Bari
  • Bologna, Italy, 40138
    • Policlinico Sant Orsola-Malpighi
  • Genova, Italy, 16147
    • IRCCS Istituto Giannina Gaslini (39012)
  • Messina, Italy, 98125
    • Universita degli Studi di Messina
  • Milano, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20156
    • Istituto di Ricerche Farmacologiche Mario Negri IRCCS
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universitaria di Padova (39011)
  • Pavia, Italy, 27100
    • Instituti Clinici Scientifici Maugeri SPA-IRCCS
  • Rome, Italy, 00165
    • Ospedale Pediatrico Bambino Gesù
• Japan
  • Osaka, Japan, 530-8480
    • Kitano Hospital
  • Tokyo, Japan, 181-8611
    • Kyorin University Hospital (81009)
  • Aichi
    • Nagoya-shi, Aichi, Japan, 466-8560
      • Nagoya University Hospital (81003)
    • Ōbu, Aichi, Japan, 474-8710
      • Aichi Children's Health and Medical Center
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital (81006)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 9208650
      • NHO Kanazawa Medical Center
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital (81005)
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8558
      • Seirei Hamamatsu General Hospital (81004)
• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Yonsei University College of Medicine, Sinchon Severance Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital (82005)
  • Soeul, Korea, Republic of, 03080
    • Seoul National University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Emma Kinderziekenhuis, Amsterdam UMC
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Nijmegen, Netherlands, 6500 HB
    • Radboud University Medical Center
• Poland
  • Łódź, Poland, 90-153
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Łódź, Poland, 92-213
    • SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Barcelona, Spain, 08035
    • Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica
  • Barcelona, Spain, 08950
    • Hospital Materno Infantil Sant Joan de Deu
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre, Nephrology Department
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Sevilla, Spain, 41013
    • University Hospital of Virgen del Rocio
  • Valencia, Spain, 46017
    • Hospital Universitario Dr Peset
• Switzerland
  • Bern, Switzerland, CH-3010
    • Inselspital, Bern University Hospital
  • Lausanne, Switzerland, CH-1011
    • CHUV Lausanne
  • Zürich, Switzerland, CH-8091
    • Universitatsspital Zurich
• United Kingdom
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucestershire Hospitals NHS Foundation Trust
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS trust (44003)
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust (44015)
  • London, United Kingdom, SE1 7EH
    • Evelina London Children Hospital (44016)
  • London, United Kingdom, SW17 0QT
    • St George'Äôs University Hospitals NHS Foundation Trust (44014)
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine, University of Southern California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (01035)
    • Orange, California, United States, 92868
      • UCI Center for Clinical Research
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center (Transplant Research) (01016)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School Of Medicine
    • Atlanta, Georgia, United States, 30342
      • Fides Clinical Research, LLC (01042)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Institute for Public Health and Medicine Northwestern University Northwestern University (01041)
    • Oak Brook, Illinois, United States, 60523
      • NANIU Research Chicago (01040)
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Nephrology Associates of Northern IL and Inn (01043)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital (01013)
    • Springfield, Massachusetts, United States, 01107
      • Renal and Transplant Associates of New England, PC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64102
      • Children's Mercy Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridian Health
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen Children Hospital
    • New York, New York, United States, 10032
      • CUIMC - Columbia Nephrology
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (01038)
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
  • Texas
    • El Paso, Texas, United States, 79902
      • MedResearch Inc
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 812 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Pegcetacoplan; Complement (C3) Inhibitor
Placebo Comparator: Group 2: Placebo administration; Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly	Other: Placebo; Sterile solution of equal volume to active arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The log-transformed ratio of uPCR at week 26 compared to baseline	Baseline to week 26

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of participants who meet the criteria for achieving a composite renal endpoint (a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and a ≥50% reduction in uPCR compared to the baseline visit.)	Baseline to week 26
The proportion of participants with a reduction of at least 50% from baseline in uPCRF	Baseline to week 26
Change from baseline in eGFR	Baseline to week 26
For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score	Baseline to week 26
The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline	Baseline to week 26

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Glomerulonephritis, Membranoproliferative
• Other Study ID Numbers: APL2-C3G-310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No