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

Inclusion Criteria:

1. Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing atleast 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:

4. In adults or adolescents with a baseline renal biopsy (either one collectedduring screening or a historic biopsy collected within 28 weeks prior torandomization), at least 2+ C3c staining on the baseline renal biopsy.

5. In adolescents not providing a baseline renal biopsy, at least one of thefollowing:

• 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 byhematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysisof urine.
• Presence of C3 nephritic factor within 6 months of screening, based oncentral laboratory results or medical history.

4. No more than 50% global glomerulosclerosis or interstitial fibrosis on the baselinebiopsy for adult participants or adolescent participants providing a baselinebiopsy.

5. At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCRof at least 1000 mg/g in at least 2 first-morning spot urine samples collectedduring screening.

6. eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-EpidemiologyCollaboration creatinine equation for adults or the Bedside Schwartz equation foradolescents.

7. Stable regimen for C3G/IC-MPGN treatment, as described below:

8. Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/orsodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized,in the opinion of the investigator, for at least 12 weeks prior torandomization

9. Stable doses of other medications that can affect proteinuria (eg, steroids,mycophenolate mofetil, and/or other allowed immunosuppressants that theparticipant is receiving for treatment of C3G or IC-MPGN) for at least 812weeks prior to the baseline renal biopsy and randomization.

10. If a participant is on prednisone (or other systemic corticosteroid) for C3G orIC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (orequivalent dosage of a corticosteroid other than prednisone) for at least 12weeks prior to randomization.

11. 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 toreceive vaccinations during screening.

Exclusion Criteria:

1. Previous exposure to pegcetacoplan.

2. C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonalgammopathy, a systemic autoimmune disease such as systemic lupus erythematosus,chronic antibody-mediated rejection, or a medication), in the opinion of theinvestigator.

3. Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV),or hepatitis C (HCV) infection or positive serology during screening that isindicative 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:

8. Cured basal or squamous cell skin cancer

9. Curatively treated in situ disease

10. Malignancy-free and off treatment for ≥5 years

11. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to thefirst dose of pegcetacoplan.

12. An absolute neutrophil count <1000 cells/mm3 at screening.

13. Use of rituximab, belimumab, or any approved or investigational anticomplementtherapy other than pegcetacoplan within 5 half-lives of that product prior to thescreening period.

14. Female participants who are pregnant or who are currently breastfeeding and areunwilling to discontinue for the duration of the study and for at least 90 daysafter the final dose of study drug.

15. Presence or suspicion of severe infection during the screening period (including butnot limited to recurrent or chronic infections) that, in the opinion of theinvestigator, may place the participant at unacceptable risk by study participation.

16. Known or suspected hereditary fructose intolerance.