A phase 3, randomized, placebo-controlled, double-blinded, multicenter study to evaluate the efficacy and safety of pegcetacoplan in patients with C3 glomerulopathy or immune-complex membranoproliferative glomerulonephritis

Phase 3

Recruiting

• Conditions: glomerulus diseases; kidney diseases; 10029149

• Registration Number: NL-OMON55956
• Lead Sponsor: Apellis Pharmaceuticals, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 5

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 (either one collected
during screening or a historic biopsy collected within 28 weeks prior to
randomization), 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:
- 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 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 participants or adolescent participants providing a
baseline biopsy.
5. At least 1 g/day of proteinuria on a screening 24-hour urine collection and
a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples
collected during screening.
6. eGFR >=30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-
Epidemiology Collaboration 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,
and/or sodium-glucose cotransporter-2 inhibitor 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
participant is receiving for treatment of C3G or IC-MPGN) for at least 12 weeks
prior to randomization.
c. If a participant is on prednisone (or other systemic corticosteroid) for C3G
or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or
equivalent dosage of a corticosteroid other than prednisone) for 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) as per ACIP recommendations for adults
or children with complement deficiencies. Vaccination series should be
initiated at least 14 days prior to randomization. Vaccination is mandatory
unless documented evidence exists that participants are nonresponders to
vaccination.
9. Female participants 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 participants must agree to use protocol-defined methods of
contraception and agree to r

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. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior
to the first dose of pegcetacoplan.
11. An absolute neutrophil count <1000 cells/mm3 at screening
12. Significant other renal disease that would, in the opinion of the
investigator, confound interpretation of study results.
13. 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.
14. 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.
15. Female participants 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.
16. Inability to cooperate or any condition that, in the opinion of the
investigator, creates an undue risk for the participant by participating in the
study or is likely to confound interpretation of the study results.
17. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of
the investigator.
18. Presence or suspicion of severe infection during the screening period
(including but not limited to recurrent) or chronic infections that, in the
opinion of the investigator, may place the participant at unacceptable risk by
study participation.
19. Known or suspected hereditary fructose intolerance.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy endpoint is the log-transformed ratio of urine<br /><br>protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline.</p><br>