Clinical trial NCT05067127: Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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)
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 124
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The log-transformed ratio of uPCR at week 26 compared to baseline
timeFrame: Baseline to week 26
Secondary outcomes:
measure: 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.)
timeFrame: Baseline to week 26
measure: The proportion of participants with a reduction of at least 50% from baseline in uPCR
timeFrame: Baseline to week 26
measure: For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score
timeFrame: Baseline to week 26
measure: The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline
timeFrame: Baseline to week 26
measure: Change from baseline in eGFR
timeFrame: Baseline to week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine, University of Southern California
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (01035)
state: California
city: Orange
country: United States
facility: UCI Center for Clinical Research
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center (Transplant Research) (01016)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Fides Clinical Research, LLC (01042)
state: Georgia
city: Chicago
country: United States
facility: Institute for Public Health and Medicine Northwestern University Northwestern University (01041)
state: Illinois
city: Oak Brook
country: United States
facility: NANIU Research Chicago (01040)
state: Illinois
city: Fort Wayne
country: United States
facility: Nephrology Associates of Northern IL and Inn (01043)
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa
state: Iowa
city: Boston
country: United States
facility: Boston Children's Hospital (01013)
state: Massachusetts
city: Springfield
country: United States
facility: Renal and Transplant Associates of New England, PC
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: New Hyde Park
country: United States
facility: Cohen Children Hospital
state: New York
city: New York
country: United States
facility: CUIMC - Columbia Nephrology
state: New York
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (01038)
state: Oregon
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: El Paso
country: United States
facility: MedResearch Inc
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Córdoba
country: Argentina
facility: Hospital Privado-Universitario de Cordoba
city: Córdoba
country: Argentina
facility: Clinica Privada Velez Sarsfield
city: Garran
country: Australia
facility: Canberra Hospital - Renal Clinical Trials & Research Unit
state: Australian Capital Territory
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Monash University
city: Fitzroy
country: Australia
facility: St. Vincents Melbourne
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Innsbruck
country: Austria
facility: Medical University Hospital Innsbruck (43004)
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Bruxelles
country: Belgium
facility: Hopital Erasme HUB Service Pharmacie
city: Edegem
country: Belgium
facility: University Hospital Antwerp (32004)
city: Leuven
country: Belgium
facility: Catholic University of Leuven
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Liège
country: Belgium
facility: Clinical Trials CHU de Liège
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: Minas Gerais
city: Juiz De Fora
country: Brazil
facility: Centro de Tratamento de Doencas Renais
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: RS
city: Botucatu
country: Brazil
facility: HC UNESP Botucatu
city: Fortaleza
country: Brazil
facility: Hospital Universitario Walter Cantidio
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Recife
country: Brazil
facility: Real Hospital Portuguas de Beneficancia em Pernambuco
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas de Ribeirao Preto, Division of Nephrology
city: Rio De Janeiro
country: Brazil
facility: Nefrologia I-Dor
city: Rio De Janeiro
country: Brazil
facility: Ruschel Medicina E Pesquisa Clinica
city: São José Do Rio Preto
country: Brazil
facility: Hospital de Base
city: São Paulo
country: Brazil
facility: UNIFESP - Hospital Sao Paulo
city: São Paulo
country: Brazil
facility: Instituto da Crianca-Hospital das Clinicas University of Sao Paulo
city: São Paulo
country: Brazil
facility: HCFMUSP-Hospital Clinicas da Faculdade Medicina da Universidade de São Paulo
city: Toronto
country: Canada
facility: Hospital for Sick Children (11003)
state: Ontario
city: Montréal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
city: Prague
country: Czechia
facility: Faculty Hospital Kralovske Vinohrady (42002)
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hopital Pellegrin
city: Créteil
country: France
facility: Hopital Henri-Mondor
city: Lyon
country: France
facility: Hospital Edouard Herriot, Hospices Civils de Lyon
city: Montpellier
country: France
facility: CHU Montpellier, Hopital Lapeyronie
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology
city: Paris
country: France
facility: Hopital Necker (33014)
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
city: Saint-Priest-en-Jarez
country: France
facility: CHU de Saint Etienne, Hospital Nord
city: Strasbourg
country: France
facility: University Hospital Strasbourg
city: Toulouse
country: France
facility: Rangueil Hospital-University Hospital Center (CHU) of Toulouse
city: Berlin
country: Germany
facility: Charite Universitatsmedizin (49007)
city: Essen
country: Germany
facility: Universitatsklinikum Essen (AoR), Zentrum fur Kinder (49005)
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen
city: Mainz
country: Germany
facility: Universitatsmedizin Mainz
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Regensburg
country: Germany
facility: University Hospital Regensburg (49004)
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Petah Tikva
country: Israel
facility: Institute of Pediatric Nephrology
city: Bari
country: Italy
facility: Policlinico di Bari
city: Bologna
country: Italy
facility: Policlinico Sant Orsola-Malpighi
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini (39012)
city: Messina
country: Italy
facility: Universita degli Studi di Messina
city: Milano
country: Italy
facility: Istituto di Ricerche Farmacologiche Mario Negri IRCCS
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova (39011)
city: Pavia
country: Italy
facility: Instituti Clinici Scientifici Maugeri SPA-IRCCS
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital (81003)
state: Aichi
city: Ōbu
country: Japan
facility: Aichi Children's Health and Medical Center
state: Aichi
city: Maebashi
country: Japan
facility: Gunma University Hospital (81006)
state: Gunma
city: Kanazawa
country: Japan
facility: NHO Kanazawa Medical Center
state: Ishikawa
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital (81005)
state: Nagasaki
city: Hamamatsu
country: Japan
facility: Seirei Hamamatsu General Hospital (81004)
state: Shizuoka
city: Osaka
country: Japan
facility: Kitano Hospital
city: Tokyo
country: Japan
facility: Kyorin University Hospital (81009)
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine, Sinchon Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (82005)
city: Soeul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Amsterdam
country: Netherlands
facility: Emma Kinderziekenhuis, Amsterdam UMC
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Łódź
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
city: Łódź
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
city: Barcelona
country: Spain
facility: Fundació Puigvert
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica
city: Barcelona
country: Spain
facility: Hospital Materno Infantil Sant Joan de Deu
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre, Nephrology Department
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: University Hospital of Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario Dr Peset
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital
city: Lausanne
country: Switzerland
facility: CHUV Lausanne
city: Zürich
country: Switzerland
facility: Universitatsspital Zurich
city: Gloucester
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS trust (44003)
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust (44015)
city: London
country: United Kingdom
facility: Evelina London Children Hospital (44016)
city: London
country: United Kingdom
facility: St George'Äôs University Hospitals NHS Foundation Trust (44014)
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital Foundation Trust
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham Children's Hospital
Study officials:
References: