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

Phase 2

Active, not recruiting

Conditions: Renal Transplant
Dense Deposit Disease (DDD)
Membranoproliferative Glomerulonephritis (MPGN)
Complement 3 Glomerulonephritis
Membranoproliferative Glomerulonephritis
C3 Glomerulonephritis
C3G
Complement 3 Glomerulopathy
Complement 3 Glomerulopathy (C3G)
Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

Interventions: Drug: Pegcetacoplan

Registration Number: NCT04572854

Lead Sponsor: Apellis Pharmaceuticals, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 13

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2	Pegcetacoplan	No intervention given during the randomized controlled portion of the study (through week 12). After week 12, subjects will receive pegcetacoplan treatment.
Group 1	Pegcetacoplan	Pegcetacoplan treatment of 1080 mg (sub-cutaneous infusion) twice weekly will be given throughout the entire study.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12	Baseline (Day 1) and 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52	Baseline (Day 1) and 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.
Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52	Baseline (Day 1), Week 12 and 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. 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.
Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Baseline (Day 1) and 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.
Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52	Baseline (Day 1) and 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.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Baseline (Day 1) and 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.
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Baseline (Day 1) and 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.
Change From Baseline in Serum Creatinine Concentration at Week 52	Baseline (Day 1) and 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.
Percentage Change From Baseline in Serum Creatinine Concentration at Week 52	Baseline (Day 1) and 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.

Trial Locations

Locations (25): Istituto di Ricerche Farmacologiche Mario Negri IRCCS
🇮🇹
Ranica, Italy
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Mayo Clinic Arizona
🇺🇸
Phoenix, Arizona, United States
Freeman Hospital
🇬🇧
Newcastle Upon Tyne, United Kingdom
Keck School of Medicine, University of Southern California
🇺🇸
Los Angeles, California, United States
Hospital Universitario Fundacion Favaloro
🇦🇷
Buenos Aires, Argentina
Washington University, St.Louis
🇺🇸
Saint Louis, Missouri, United States
Hospital de Alta Complejidad en Red El Cruce Dr. Nestor Carlos Kirchner
🇦🇷
Florencio Varela, Provincia De Buenos Aires, Argentina
CUIMC
🇺🇸
New York, New York, United States
NYU Langone Health Transplant Insitute
🇺🇸
New York, New York, United States
The Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
Hopital Edouard Herriot, Hospices Civils de Lyon
🇫🇷
Lyon, France
Medical University of Vienna
🇦🇹
Vienna, Austria
Monash Medical Centre
🇦🇺
Clayton, Australia
Clinical Research Center, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷
São Paulo, Brazil
Center Hospitalier Universitaire de Montpellier
🇫🇷
Montpellier, France
UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
🇧🇷
Botucatu, Sao Paulo, Brazil
Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology
🇫🇷
Lille, France
Radbound University Medical Center
🇳🇱
Nijmegen, Netherlands
Hospital Universitario 12 de Octubre, Nephrology Department
🇪🇸
Madrid, Spain
CHUV
🇨🇭
Lausanne, Switzerland
Imperial College Healthcare NHS Trust
🇬🇧
London, United Kingdom
Irmandade da Santa Casa de Misericordia de Porto Alegre
🇧🇷
Porto Alegre, RS, Brazil
Santa Casa de Misericordia de Belo Horizonte
🇧🇷
Belo Horizonte, Brazil
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States