C3G, C3 Glomerulonephritis, C3 Glomerulopathy, Complement 3 Glomerulonephritis, Complement 3 Glomerulopathy, Complement 3 Glomerulopathy (C3G), Dense Deposit Disease (DDD), IC-MPGN, Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN), Membranoproliferative Glomerulonephritis, Membranoproliferative Glomerulonephritis (MPGN), Renal Transplant
Conditions
Brief summary
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.
Interventions
DRUGPegcetacoplan
Complement (C3) Inhibitor
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12 | Baseline (Day 1) and Week 12 | C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52 | Baseline (Day 1) and Week 52 | C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Baseline (Day 1), Week 12 and Week 52 | C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. Number of subjects who demonstrated a shift of C3c staining from baseline to Week 12 and baseline to Week 52 are presented. |
| Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | Baseline (Day 1) and Week 52 | eGFR was calculated by using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation. Stabilization or improvement in eGFR was defined as no more than a 25% decrease relative to baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52 | Baseline (Day 1) and Week 52 | Stabilization or improvement in serum creatinine was defined as no increase or an increase of no more than 25% from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | Baseline (Day 1) and Week 52 | Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | Baseline (Day 1) and Week 52 | Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Change From Baseline in Serum Creatinine Concentration at Week 52 | Baseline (Day 1) and Week 52 | Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
| Percentage Change From Baseline in Serum Creatinine Concentration at Week 52 | Baseline (Day 1) and Week 52 | Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. |
Countries
Argentina, Australia, Austria, Brazil, France, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This phase 2, open-label study was conducted in subjects with post-transplant recurrence of complement 3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN) at 23 sites across 11 countries. First subject was recruited on 07 September 2021 and data cut-off (DCO) date was 19 January 2024.
Pre-assignment details
The study consisted of 2 parts: Part A core study (controlled and non-controlled portion) and Part B long-term extension. A total of 13 subjects were enrolled in the study. Results are presented based on DCO date of 19 January 2024 for Part A. Subjects who experienced clinical benefit from pegcetacoplan administration could participate in part B, a long-term extension, to continue receiving pegcetacoplan until it is commercially available for the disease under study.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Controlled Portion: Group 1 Subjects received pegcetacoplan 1080 mg twice weekly via SC infusion on Day 1 and Day 4 of each treatment week until Week 12. | 10 |
| Part A: Controlled Portion: Group 2 Subjects did not receive any pegcetacoplan treatment until Week 12. | 3 |
| Total | 13 |
Baseline characteristics
| Characteristic | Part A: Controlled Portion: Group 2 | Total | Part A: Controlled Portion: Group 1 |
|---|---|---|---|
| Age, Continuous | 44.3 Years STANDARD_DEVIATION 24.03 | 40.8 Years STANDARD_DEVIATION 14.8 | 39.8 Years STANDARD_DEVIATION 12.59 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 Participants | 11 Participants | 9 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 3 | 0 / 10 | 0 / 3 |
| other Total, other adverse events | 7 / 10 | 3 / 3 | 8 / 10 | 3 / 3 |
| serious Total, serious adverse events | 5 / 10 | 0 / 3 | 5 / 10 | 0 / 3 |
Outcome results
Primary
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12
C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 12
Population: The ITT population included all subjects who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12 | 50.0 Percentage of participants |
| Part A: Controlled Portion: Group 2 | Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 12 | 33.3 Percentage of participants |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized. Only subjects with data collected at baseline and Week 52 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Controlled Portion: Group 1 | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | 10.1 milliliter/minute/1.73 square meter | Standard Deviation 32.67 |
| Part A: Controlled Portion: Group 2 | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | -10.3 milliliter/minute/1.73 square meter | Standard Deviation 14.57 |
Secondary
Change From Baseline in Serum Creatinine Concentration at Week 52
Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized. Only subjects with data collected at baseline and Week 52 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Controlled Portion: Group 1 | Change From Baseline in Serum Creatinine Concentration at Week 52 | -0.044 milligram per deciliter | Standard Deviation 0.8368 |
| Part A: Controlled Portion: Group 2 | Change From Baseline in Serum Creatinine Concentration at Week 52 | 0.267 milligram per deciliter | Standard Deviation 0.4619 |
Secondary
Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52
C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects. Number of subjects who demonstrated a shift of C3c staining from baseline to Week 12 and baseline to Week 52 are presented.
Time frame: Baseline (Day 1), Week 12 and Week 52
Population: The ITT population included all subjects who were randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 0 at Week 12 | 3 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 0 at Week 52 | 4 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 1 at Week 12 | 1 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 0 at Week 52 | 0 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 0 at Week 12 | 1 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 1 at Week 52 | 1 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 3 at Week 52 | 1 Participants |
| Part A: Controlled Portion: Group 1 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 3 at Week 12 | 0 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 3 at Week 52 | 0 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 0 at Week 12 | 0 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 0 at Week 12 | 0 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 1 at Week 12 | 1 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 3 at Week 12 | 1 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 0 at Week 52 | 1 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 2 at baseline to 0 at Week 52 | 1 Participants |
| Part A: Controlled Portion: Group 2 | Number of Subjects With Shift of C3c Staining From Baseline to Weeks 12 and 52 | Shift from 3 at baseline to 1 at Week 52 | 0 Participants |
Secondary
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
Blood samples were collected at specified timepoints for analysis of eGFR which was calculated by using CKD-EPI creatinine equation. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized. Only subjects with data collected at baseline and Week 52 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | 29.65 percentage change | Standard Deviation 78.707 |
| Part A: Controlled Portion: Group 2 | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | -16.67 percentage change | Standard Deviation 21.481 |
Secondary
Percentage Change From Baseline in Serum Creatinine Concentration at Week 52
Blood samples were collected at specified timepoints for analysis of serum creatinine concentration. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized. Only subjects with data collected at baseline and Week 52 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage Change From Baseline in Serum Creatinine Concentration at Week 52 | 3.198 percentage change | Standard Deviation 59.5916 |
| Part A: Controlled Portion: Group 2 | Percentage Change From Baseline in Serum Creatinine Concentration at Week 52 | 17.778 percentage change | Standard Deviation 30.792 |
Secondary
Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52
C3c staining intensity is semi quantitatively graded on a scale of 0 to 3, in which negative, 1+, 2+ and 3+ staining corresponds to scores of 0 to 3, with 0 being absent and 3 being the highest intensity seen on immunofluorescence. Higher scores indicate worse outcome. Reduction in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52 | 50.0 Percentage of participants |
| Part A: Controlled Portion: Group 2 | Percentage of Subjects With Reduction in C3c Staining on Renal Biopsy at Week 52 | 66.7 Percentage of participants |
Secondary
Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52
eGFR was calculated by using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation. Stabilization or improvement in eGFR was defined as no more than a 25% decrease relative to baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | 70.0 Percentage of participants |
| Part A: Controlled Portion: Group 2 | Percentage of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) at Week 52 | 66.7 Percentage of participants |
Secondary
Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52
Stabilization or improvement in serum creatinine was defined as no increase or an increase of no more than 25% from baseline. Baseline was defined as the most recent non-missing measurement prior to first administration of study drug for Group 1 subjects or randomization for Group 2 subjects.
Time frame: Baseline (Day 1) and Week 52
Population: The ITT population included all subjects who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Controlled Portion: Group 1 | Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52 | 70.0 Percentage of participants |
| Part A: Controlled Portion: Group 2 | Percentage of Subjects With Stabilization or Improvement of Serum Creatinine Concentration at Week 52 | 66.7 Percentage of participants |