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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Drug: Pegcetacoplan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the proportion of subjects with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. |  | 12 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with reduction in C3c staining on renal biopsy |  | 52 weeks after randomization | 
| The proportion of subjects with stabilization or improvement in estimated glomerular filtration rate (eGFR) |  | 52 weeks after randomization | 
| The proportion of subjects with stabilization or improvement of serum creatinine concentration |  | 52 weeks after randomization |