complement 3 glomerulopathy (C3G)/immune complex membranoproliferative glomerulonephritis (IC-MPGN) MedDRA version: 20.0 Level: SOC Classification code 10038359 Term: Renal and urinary disorders System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: PT Classification code 10077827 Term: C3 glomerulopathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 21.1 Level: LLT Classification code 10027168 Term: Membranoproliferative glomerulone
Conditions
Interventions
Product Name: Pegcetacoplan
Product Code: APL-2
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Pegcetacoplan
CAS Number: 2019171-69-6
Current Sponsor code: APL-2
Concentrat
Sponsors
Apellis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 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: a. In adults or adolescents with a baseline renal biopsy, at least 2+ C3c staining on the baseline renal biopsy b. In adolescents not providing a baseline renal biopsy, at least one of the following: - Serum C5b-9 level above the upper limit of normal during screening - Serum C3 below the lower limit of normal (LLN) during screening - Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells per high-power field and/or red blood cell casts on routine local or central microscopic analysis of urine - Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history 4. No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult subjects or adolescent subjects providing a baseline biopsy. 5. At least 1 g/d of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g on at least 2 FMU samples collected during screening. 6. eGFR =30 mL/min/1.73 m2 calculated by the CKD-EPI creatinine equation for adults or the Bedside Schwartz equation for adolescents. 7. Stable regimen for C3G/IC-MPGN treatment, as described below: a. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization b. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the patient is receiving for treatment of C3G) for at least 8 weeks prior to the baseline renal biopsy and at least 12 weeks prior to randomization. c. If a subject is on prednisone (or other systemic corticosteroid) for C3G/IC-MPGN treatment, the dosage is stable and no higher than 20 mg/d (or equivalent dosage of a corticosteroid other than prednisone) for at least 8 weeks prior to the baseline renal biopsy and at least 12 weeks prior to randomization. 8. 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 to receive vaccinations during screening. Vaccination series should be initiated at least 14 days prior to randomization. Vaccination is mandatory unless documented evidence exists that subjects are nonresponders to vaccination. 9. Female subjects of childbearing potential, defined as any women who have experienced menarche and who are not permanently sterile or postmenopausal, must have negative blood pregnancy tests at screening (and negative urine pregnancy tests on Day 1) and must agree to use protocol-defined methods of contraception from screening through at least 90 days after receiving the last dose of pegcetacoplan. 10. Male subjects must agree to use protocol-defined methods of contraception and agree to refrain from donating semen from screening through at least 90 days after receiving the last dose of pegcetacoplan. 11. Subjects above the legal age of consent, in accordance with local regulations, must be willing and able to provide informed consent. The legally authorized representative of subjects under the legal age of c
Exclusion criteria
Exclusion criteria: 1. Previous exposure to pegcetacoplan. 2. Evidence of improving renal disease in the 8 weeks prior to screening or during the screening period according to available data; improving renal disease is defined as >30% increase in eGFR or >50% decrease in proteinuria. 3. From a renal transplant subject, evidence of rejection that requires treatment in the baseline renal biopsy collected during screening. 4. C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator. 5. Current or prior diagnosis of HIV, hepatitis B, or hepatitis C infection or positive serology during screening that is indicative of infection with any of these viruses. 6. Weight more than 100 kg at screening. 7. Hypersensitivity to pegcetacoplan or to any of the excipients. 8. History of meningococcal disease. 9. Malignancy, except for the following: a. Cured basal or squamous cell skin cancer b. Curatively treated in situ disease c. Malignancy-free and off treatment for =5 years 10. An absolute neutrophil count less than 1000 cells/mm3 at screening. 11. Significant other renal disease that would, in the opinion of the investigator, confound interpretation of study results. 12. 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 investigational agent (whichever is longer) prior to screening period. 13. Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period. 14. Female subjects who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug. 15. Inability to cooperate or any condition that, in the opinion of the investigator, creates an undue risk for the subject by participating in the study or is likely to confound interpretation of the study results. 16. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of the investigator. 17. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the investigator, may place the subject at unacceptable risk by study participation. 18. Known or suspected hereditary fructose intolerance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: •To assess the effect of pegcetacoplan on eGFR •To assess the effect of pegcetacoplan on additional C3G/IC-MPGN disease–related parameters •To evaluate the safety of pegcetacoplan over 52 weeks of treatment;Primary end point(s): The primary efficacy endpoint is The proportion of subjects with a reduction from baseline in uPCR of at least 50%. The primary and secondary endpoints will be evaluated at Week 26. The primary and secondary endpoints will also be evaluated at Week 52 as exploratory endpoints;Timepoint(s) of evaluation of this end point: Weeks 26 and 52;Main Objective: The primary objective of this study is to assess the efficacy of twice-weekly SC doses of pegcetacoplan compared with that of placebo in patients with primary C3G or IC-MPGN on the basis of a reduction in proteinuria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •The proportion of subjects with eGFR values that are stable or improved from baseline For subjects with evaluable renal biopsies, the change from baseline in the C3G histologic activity index score (Bomback et al. 2018) The proportion of subjects with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline The proportion of subjects achieving proteinuria <1 g/d Change from baseline in uPCR Change from baseline in eGFR For subjects with serum albumin levels below the LLN at baseline, the proportion of subjects with normalization of serum albumin levels For subjects with serum C3 levels below the LLN at baseline, the proportion of subjects with serum C3 levels above the LLN The change from baseline in the FACIT-Fatigue Scale score The change from baseline in the KDQOL score The primary and secondary endpoints will be evaluated at Week 26. The primary and secondary endpoints will also be evaluated at Week 52 as exploratory endpoints;Timepoint(s) of evaluation of this end point: Weeks 26 and 52 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Czech Republic, Finland, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Peru, Poland, Spain, Switzerland, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial
Apellis Pharmaceuticals, Inc.
Outcome results
None listed