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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apellis Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

4 Apr 2022 → 14 Jan 2025

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Apellis Pharmaceuticals Inc.

External identifiers

EU CT number

2024-514130-20-00

EudraCT number

2020-003767-25

ClinicalTrials.gov

NCT05067127

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 objectives 3

1. To assess the effect of pegcetacoplan on eGFR
2. To assess the effect of pegcetacoplan on additional C3G/IC-MPGN disease–related parameters
3. To evaluate the safety of pegcetacoplan over 52 weeks of treatment

Conditions and MedDRA coding

complement 3 glomerulopathy (C3G)/immune complex membranoproliferative glomerulonephritis (IC-MPGN)

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Requests for access to the deidentified data will be reviewed by Apellis External Research Committee.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 informed consent. The legally authorized representative of participants under the legal age of consent must be willing and able to provide informed consent; where appropriate, participants under the legal age of consent must also give their assent to participation in the study.
12. Willing and able to self-administer pegcetacoplan or have an identified caregiver who can perform the administration.

Exclusion criteria 19

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the log-transformed ratio of uPCR at week 26 compared to baseline.

Secondary endpoints 10

1. 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.)
2. The proportion of participants with a reduction of at least 50% from baseline in uPCR
3. For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score (Bomback et al. 2018)
4. The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline
5. hange from baseline in eGFR
6. The proportion of participants achieving proteinuria <1 g/day
7. For participants with serum albumin levels below the LLN at baseline, the proportion of participants with normalization of serum albumin levels
8. For participants with serum C3 levels below the LLN at baseline, the proportion of participants with serum C3 levels above the LLN
9. The change from baseline in the FACIT-Fatigue Scale score
10. The change from baseline in the KDQOL score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Apellis Pharmaceuticals Inc.

Sponsor organisation

Apellis Pharmaceuticals Inc.

Address

100 5th Avenue

City

Waltham

Postcode

02451-8703

Country

United States

Scientific contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trials

Public contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trials

Third parties 16

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications