A Phase 3 study to Evaluate the Efficacy and Safety of Pegcetacoplan administered subcutaneously in Patients with C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2020-003767-25-NL
• Date of registration: 13/10/2021
• Prospective Registration: Yes
• Primary sponsor: Apellis Pharmaceuticals, Inc.
• Public title: A Phase 3 study to Evaluate the Efficacy and Safety of Pegcetacoplan administered subcutaneously in Patients with C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
• Scientific title: 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 - VALIANT
• Date of first enrolment: 16/02/2022
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003767-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Czechia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trial
• Affiliation: Apellis Pharmaceuticals, Inc.

• Name: Clinical Trial
• Affiliation: Apellis Pharmaceuticals, Inc.

Key inclusion & exclusion 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 (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 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 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 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, 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 refrain from donating semen from screening through at least 90 days after receiving the last dose of pegcetacoplan.
11. Participants above the legal age of consent, in accordance with local regulations, must be willing and able to provide
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 participant, 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. Body weight greater 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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 glomerulonephritis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name:
Aspaveli
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
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 54-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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 log-transformed ratio of uPCR at week 26 compared to baseline. 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.

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.

Timepoint(s) of evaluation of this end point: Weeks 26 and 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 26 and 52

Secondary end point(s): The proportion of participants who meet the criteria for achieving a composite renal
endpoint (a stable or improved eGFR compared to the baseline visit (= 15%
reduction in eGFR), and a =50% reduction in uPCR compared to the baseline visit.)
The proportion of participants with a reduction of at least 50% from baseline in uPCR
Change from baseline in eGFR
For participants with evaluable renal biopsies, the change from baseline
in the activity score of the C3G histologic index score (Bomback et al. 2018)
The proportion of participants with evaluable renal biopsies showing
decreases in C3c staining on renal biopsy from baseline.
The proportion of participants achieving proteinuria <1 g/day.
For participants with serum albumin levels below the LLN at baseline,
the proportion of participants with normalization of serum albumin levels.
For participants with serum C3 levels below the LLN at baseline, the
proportion of participant 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

Secondary ID(s)

APL2-C3G-310

2020-003767-25-DE

Source(s) of Monetary Support

Apellis Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 16/02/2022
Contact: