Clinical trial NCT04572854: Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: C3G
IC-MPGN
Renal Transplant
Complement 3 Glomerulopathy
Complement 3 Glomerulopathy (C3G)
Dense Deposit Disease (DDD)
Membranoproliferative Glomerulonephritis
Membranoproliferative Glomerulonephritis (MPGN)
Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
C3 Glomerulopathy
C3 Glomerulonephritis
Complement 3 Glomerulonephritis
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12
timeFrame: Baseline (Day 1) and Week 12
Secondary outcomes:
measure: Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52
timeFrame: Baseline (Day 1), Week 12 and Week 52
measure: Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Serum Creatinine Concentration at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Percentage Change From Baseline in Serum Creatinine Concentration at Week 52
timeFrame: Baseline (Day 1) and Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Keck School of Medicine, University of Southern California
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, St.Louis
state: Missouri
city: New York
country: United States
facility: NYU Langone Health Transplant Insitute
state: New York
city: New York
country: United States
facility: CUIMC
state: New York
city: Florencio Varela
country: Argentina
facility: Hospital de Alta Complejidad en Red El Cruce Dr. Nestor Carlos Kirchner
state: Provincia De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Fundacion Favaloro
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: RS
city: Botucatu
country: Brazil
facility: UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
state: Sao Paulo
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: São Paulo
country: Brazil
facility: Clinical Research Center, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
city: Lille
country: France
facility: Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology
city: Lyon
country: France
facility: Hopital Edouard Herriot, Hospices Civils de Lyon
city: Montpellier
country: France
facility: Center Hospitalier Universitaire de Montpellier
city: Ranica
country: Italy
facility: Istituto di Ricerche Farmacologiche Mario Negri IRCCS
city: Nijmegen
country: Netherlands
facility: Radbound University Medical Center
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre, Nephrology Department
city: Lausanne
country: Switzerland
facility: CHUV
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
References: