Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN (NOBLE)

An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC-MPGN

This is a Phase 2, multicenter, open-label, randomized, controlled study designed to evaluate the safety and efficacy of pegcetacoplan in patients who have post-transplant recurrence of C3G or IC-MPGN.

Study Overview

• Status: Completed
• Conditions: Renal Transplant; C3G; IC-MPGN; C3 Glomerulopathy; C3 Glomerulonephritis; Complement 3 Glomerulopathy; Complement 3 Glomerulopathy (C3G); Complement 3 Glomerulonephritis; Membranoproliferative Glomerulonephritis; Membranoproliferative Glomerulonephritis (MPGN); Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN); Dense Deposit Disease (DDD)
• Intervention / Treatment: Drug: Pegcetacoplan

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1093AAS
    • Hospital Universitario Fundacion Favaloro
  • Buenos Aires
    • San Juan Bautista, Buenos Aires, Argentina, B1888AAE
      • Hospital de Alta Complejidad en Red El Cruce Dr. Nestor Carlos Kirchner
• Australia
  • Clayton, Australia, 3168
    • Monash Medical Centre
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Brazil
  • Belo Horizonte, Brazil, CEP 30150-221
    • Santa Casa de Misericórdia de Belo Horizonte
  • São Paulo, Brazil, 05403-000
    • Clinical Research Center, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-686
      • UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
• France
  • Lille, France, 59000
    • Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology
  • Lyon, France, 69437
    • Hôpital Edouard Herriot, Hospices Civils de Lyon
  • Montpellier, France, 34295 CEDEX 5
    • Center Hospitalier Universitaire de Montpellier
• Italy
  • Ranica, Italy, 24020
    • Istituto di Ricerche Farmacologiche Mario Negri IRCCS
• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Radbound University Medical Center
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre, Nephrology Department
• Switzerland
  • Lausanne, Switzerland, 1005
    • CHUV
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Los Angeles, California, United States, 900033
      • Keck School of Medicine, University of Southern California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University, St.Louis
  • New York
    • New York, New York, United States, 10032
      • CUIMC
    • New York, New York, United States, 10016
      • NYU Langone Health Transplant Insitute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years of age at screening
• Must have clinical and pathologic evidence of recurrent C3G or IC-MPGN
• Stable (not improving) or worsening disease, in the opinion of the investigator, in the 2 months preceding the first dose of pegcetacoplan
• eGFR ≥15 mL/min/1.73 m2, calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation for adults
• No more than 50% glomerulosclerosis or interstitial fibrosis on the screening renal allograft biopsy
• Stable regimen for recurrent C3G/IC-MPGN for at least 4 weeks prior to the screening renal allograft biopsy and from the time of the screening renal allograft biopsy until randomization
• Have received required vaccinations against N. meningitidis, S. pneumoniae, and H. influenzae (type B) or agree to receive vaccinations, if applicable vaccination records are not available. Vaccination is mandatory unless documented evidence exists that subjects are non-responders to vaccination.

Exclusion Criteria:

• Absolute neutrophil count <1000 cells/mm3 during screening
• Previous treatment with pegcetacoplan
• Evidence of rejection on the screening renal allograft biopsy that requires treatment
• Diagnosis or history of HIV, hepatitis B, or hepatitis C infection or positive serology at screening indicative of infection with any of these viruses
• Weight more than 100 kg at screening
• Hypersensitivity to pegcetacoplan or 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
• Significant renal disease in the renal allograft secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, rejection, or a medication) that would, in the opinion of the investigator, confound interpretation of the study results
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or 5 half-lives from the last dose of the investigational agent (whichever is longer) prior to screening
• 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Pegcetacoplan treatment of 1080 mg (sub-cutaneous infusion) twice weekly will be given throughout the entire study.	Drug: Pegcetacoplan; Complement (C3) Inhibitor
Other: Group 2; No intervention given during the randomized controlled portion of the study (through week 12). After week 12, subjects will receive pegcetacoplan treatment.	Drug: Pegcetacoplan; Complement (C3) Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12	C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52	C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52	C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. Number of subjects who demonstrated a shift of C3c staining from baseline to Week 12 and baseline to Week 52 are presented.	Baseline (Day 1), Week 12 and Week 52
Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52	eGFR was calculated by using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation. Stabilization or improvement in eGFR was defined as no more than a 25% decrease relative to baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52	Stabilization or improvement in serum creatinine was defined as no increase or an increase of no more than 25% from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Change From Baseline in Serum Creatinine Concentration at Week 52	Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52
Percentage Change From Baseline in Serum Creatinine Concentration at Week 52	Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.	Baseline (Day 1) and Week 52

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): January 20, 2026

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: September 29, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, Membranoproliferative; pegcetacoplan
• Other Study ID Numbers: APL2-C3G-204

Drug and device information, study documents

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