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

Phase 3

Active, not recruiting

• Conditions: C3G; Membranoproliferative Glomerulonephritis (MPGN); IC-MPGN; Complement 3 Glomerulopathy; Complement 3 Glomerulonephritis; Dense Deposit Disease; DDD; C3 Glomerulopathy; Complement 3 Glomerulopathy (C3G); C3 Glomerulonephritis
• Interventions: Other: Placebo; Drug: Pegcetacoplan

• Registration Number: NCT05067127
• Lead Sponsor: Apellis Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-23
• Study First Submitted QC: 2021-09-23
• Study First Posted: 2021-10-05
• Study Start: 2021-11-12
• Primary Completion: 2024-06-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-25
• Last Update Posted: 2024-07-26
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2: Placebo administration	Placebo	Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly
Group 1: Pegcetacoplan administration	Pegcetacoplan	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)

Primary Outcome Measures

Name	Time	Method
The log-transformed ratio of uPCR at week 26 compared to baseline	Baseline to week 26

Secondary Outcome Measures

Name	Time	Method
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
Change from baseline in eGFR	Baseline to week 26
The proportion of participants with a reduction of at least 50% from baseline in uPCR	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

Trial Locations

Locations (123)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Emma Kinderziekenhuis, Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

IRCCS Istituto Giannina Gaslini (39012); 🇮🇹 Genova, Italy

Academic Medical Research Institute; 🇺🇸 Los Angeles, California, United States

Ronald Reagan UCLA Medical Center (01035); 🇺🇸 Los Angeles, California, United States

Hackensack Meridian Health; 🇺🇸 Hackensack, New Jersey, United States

Boston Children's Hospital (01013); 🇺🇸 Boston, Massachusetts, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

CUIMC - Columbia Nephrology; 🇺🇸 New York, New York, United States

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Australia

NANIU Research Chicago (01040); 🇺🇸 Oak Brook, Illinois, United States

Cohen Children Hospital; 🇺🇸 New Hyde Park, New York, United States

Hopital Necker (33014); 🇫🇷 Paris, France

Nephrology Associates of Northern IL and Inn (01043); 🇺🇸 Fort Wayne, Indiana, United States

Institute for Public Health and Medicine Northwestern University Northwestern University (01041); 🇺🇸 Chicago, Illinois, United States

The University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Renal and Transplant Associates of New England, PC; 🇺🇸 Springfield, Massachusetts, United States

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Catholic University of Leuven; 🇧🇪 Leuven, Belgium

MedResearch Inc; 🇺🇸 El Paso, Texas, United States

Hospital Universitario Walter Cantidio; 🇧🇷 Fortaleza, Brazil

Keck School of Medicine, University of Southern California; 🇺🇸 Los Angeles, California, United States

UCI Center for Clinical Research; 🇺🇸 Orange, California, United States

Canberra Hospital - Renal Clinical Trials & Research Unit; 🇦🇺 Garran, Australian Capital Territory, Australia

Emory University School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Fides Clinical Research, LLC (01042); 🇺🇸 Atlanta, Georgia, United States

Institute for Clinical and Experimental Medicine; 🇨🇿 Prague, Czechia

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology; 🇫🇷 Paris, France

Hospital Edouard Herriot, Hospices Civils de Lyon; 🇫🇷 Lyon, France

Universita degli Studi di Messina; 🇮🇹 Messina, Italy

Ruschel Medicina E Pesquisa Clinica; 🇧🇷 Rio De Janeiro, Brazil

Faculty Hospital Kralovske Vinohrady (42002); 🇨🇿 Prague, Czechia

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Monash University; 🇦🇺 Box Hill, Australia

Medizinische Universität Wien; 🇦🇹 Wien, Austria

Hospital Universitario Austral; 🇦🇷 Buenos Aires, Argentina

Hospital Privado-Universitario de Cordoba; 🇦🇷 Córdoba, Argentina

Clinica Privada Velez Sarsfield; 🇦🇷 Córdoba, Argentina

Hopital Maisonneuve-Rosemont; 🇨🇦 Montréal, Quebec, Canada

HC UNESP Botucatu; 🇧🇷 Botucatu, Brazil

Medical University Hospital Innsbruck (43004); 🇦🇹 Innsbruck, Austria

CHU Sart-Tilman; 🇧🇪 Liège, Belgium

Hôpital Européen Georges-Pompidou; 🇫🇷 Paris, France

Policlinico di Bari; 🇮🇹 Bari, Italy

Azienda Ospedaliera Universitaria di Padova (39011); 🇮🇹 Padova, Italy

Universitatsmedizin Mainz; 🇩🇪 Mainz, Germany

St. Vincents Melbourne; 🇦🇺 Fitzroy, Australia

Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen; 🇩🇪 Hannover, Germany

CHU Montpellier, Hopital Lapeyronie; 🇫🇷 Montpellier, France

Nantes University Hospital; 🇫🇷 Nantes, France

Policlinico Sant Orsola-Malpighi; 🇮🇹 Bologna, Italy

Nagasaki University Hospital (81005); 🇯🇵 Nagasaki-shi, Nagasaki, Japan

Universitatsklinikum Munster; 🇩🇪 Münster, Germany

University Hospital Strasbourg; 🇫🇷 Strasbourg, France

CHU de Bordeaux - Hopital Pellegrin; 🇫🇷 Bordeaux, France

Institute of Pediatric Nephrology; 🇮🇱 Petah Tikva, Israel

University Hospital Regensburg (49004); 🇩🇪 Regensburg, Germany

Gunma University Hospital (81006); 🇯🇵 Maebashi, Gunma, Japan

Charite Universitatsmedizin (49007); 🇩🇪 Berlin, Germany

Hospital Universitario Dr Peset; 🇪🇸 Valencia, Spain

Inselspital, Bern University Hospital; 🇨🇭 Bern, Switzerland

Hospital Universitari Vall D'Hebron; 🇪🇸 Barcelona, Spain

Hopital Henri-Mondor; 🇫🇷 Créteil, France

Yonsei University College of Medicine, Sinchon Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi; 🇵🇱 Łódź, Poland

Universitatsspital Zurich; 🇨🇭 Zürich, Switzerland

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

St George'Äôs University Hospitals NHS Foundation Trust (44014); 🇬🇧 London, United Kingdom

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

Fundació Puigvert; 🇪🇸 Barcelona, Spain

Universitatsklinikum Essen (AoR), Zentrum fur Kinder (49005); 🇩🇪 Essen, Germany

Kitano Hospital; 🇯🇵 Osaka, Japan

NHO Kanazawa Medical Center; 🇯🇵 Kanazawa, Ishikawa, Japan

Aichi Children's Health and Medical Center; 🇯🇵 Ōbu, Aichi, Japan

Great Ormond Street Hospital Foundation Trust; 🇬🇧 London, United Kingdom

CHUV Lausanne; 🇨🇭 Lausanne, Switzerland

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of

Nottingham Children's Hospital; 🇬🇧 Nottingham, United Kingdom

Kyorin University Hospital (81009); 🇯🇵 Tokyo, Japan

Nagoya University Hospital (81003); 🇯🇵 Nagoya-shi, Aichi, Japan

Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica; 🇪🇸 Barcelona, Spain

SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi; 🇵🇱 Łódź, Poland

Hospital Materno Infantil Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre, Nephrology Department; 🇪🇸 Madrid, Spain

University Hospital of Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hopital Erasme HUB Service Pharmacie; 🇧🇪 Bruxelles, Belgium

Santa Casa de Misericordia de Belo Horizonte; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Centro de Tratamento de Doencas Renais; 🇧🇷 Juiz De Fora, Minas Gerais, Brazil

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Oregon Health & Science University (01038); 🇺🇸 Portland, Oregon, United States

Istituto di Ricerche Farmacologiche Mario Negri IRCCS; 🇮🇹 Milano, Italy

Gloucestershire Hospitals NHS Foundation Trust; 🇬🇧 Gloucester, United Kingdom

University Hospitals of Leicester NHS trust (44003); 🇬🇧 Leicester, United Kingdom

Royal Free London NHS Foundation Trust (44015); 🇬🇧 London, United Kingdom

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom

Evelina London Children Hospital (44016); 🇬🇧 London, United Kingdom

CHU de Saint Etienne, Hospital Nord; 🇫🇷 Saint-Priest-en-Jarez, France

Real Hospital Portuguas de Beneficancia em Pernambuco; 🇧🇷 Recife, Brazil

Hospital das Clinicas de Ribeirao Preto, Division of Nephrology; 🇧🇷 Ribeirão Preto, Brazil

UNIFESP - Hospital Sao Paulo; 🇧🇷 São Paulo, Brazil

Hospital de Base; 🇧🇷 São José Do Rio Preto, Brazil

Instituto da Crianca-Hospital das Clinicas University of Sao Paulo; 🇧🇷 São Paulo, Brazil

HCFMUSP-Hospital Clinicas da Faculdade Medicina da Universidade de São Paulo; 🇧🇷 São Paulo, Brazil

Seirei Hamamatsu General Hospital (81004); 🇯🇵 Hamamatsu, Shizuoka, Japan

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom

Northeast Clinical Research Center, LLC; 🇺🇸 Bethlehem, Pennsylvania, United States

Irmandade da Santa Casa de Misericordia de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Nefrologia I-Dor; 🇧🇷 Rio De Janeiro, Brazil

Hospital for Sick Children (11003); 🇨🇦 Toronto, Ontario, Canada

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Rangueil Hospital-University Hospital Center (CHU) of Toulouse; 🇫🇷 Toulouse, France

Instituti Clinici Scientifici Maugeri SPA-IRCCS; 🇮🇹 Pavia, Italy

Ospedale Pediatrico Bambino Gesu; 🇮🇹 Rome, Italy

Seoul National University Hospital (82005); 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Soeul, Korea, Republic of

UC Davis Medical Center (Transplant Research) (01016); 🇺🇸 Sacramento, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Clinical Trials CHU de Liège; 🇧🇪 Liège, Belgium

University Hospital Antwerp (32004); 🇧🇪 Edegem, Belgium