An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC‑MPGN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apellis Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

21 Dec 2021 → 20 Jan 2026

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511544-36-00

EudraCT number

2020-002637-15

ClinicalTrials.gov

NCT04572854

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

To evaluate the efficacy of pegcetacoplan in improving the underlying pathophysiology of complement 3 glomerulopathy (C3G)/immune complex membranoproliferative lomerulonephritis (IC-MPGN) after 12 weeks of treatment.

Secondary objectives 2

1. To evaluate the effect of pegcetacoplan on key clinical manifestations of the disease after 52 weeks of treatment.
2. To evaluate the safety of pegcetacoplan for up to 52 weeks in patients with recurrent C3G/IC-MPGN in a renal allograft.

Conditions and MedDRA coding

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

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. At least 18 years of age at screening
2. Must have clinical and pathologic evidence of recurrent C3G or ICMPGN, as evidenced by all of the following: a. A diagnosis of C3G or IC-MPGN, with at least 2+ staining for C3c in the renal allograft, confirmed by a central pathologist, based on the screening renal allograft biopsy b. C3G or IC-MPGN must be primary and not secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, autoimmunity, chronic antibody-mediated rejection, chronic thrombotic microangiopathy, or a medication)
3. Stable (not improving) or worsening disease, in the opinion of the investigator, in the 2 months preceding the first dose of pegcetacoplan
4. eGFR ≥15 mL/min/1.73 m2, calculated by the Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) creatinine equation for adults
5. No more than 50% glomerulosclerosis or interstitial fibrosis on the screening renal allograft biopsy
6. 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
7. 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 nonresponders to vaccination.
8. Women of childbearing potential, defined as any women who have experienced menarche and who are not permanently sterile or postmenopausal, must each have a negative blood pregnancy test at screening (and negative urine pregnancy at Visit 4) and must agree to use protocol-defined methods of contraception from screening through 12 weeks after receiving last dose of pegcetacoplan
9. Men must agree to use protocol-defined methods of contraception and agree to refrain from donating semen from screening through 12 weeks after receiving last dose of pegcetacoplan
10. Willing and able to provide written informed consent
11. Able to understand and willing to comply with all scheduled procedures and other requirements of the study in the opinion of the investigator
12. Willing and able to self-administer pegcetacoplan or have an identified caregiver who can perform the administration

Exclusion criteria 14

1. Absolute neutrophil count <1000 cells/mm3 during screening (not including Day 1)
2. Previous treatment with pegcetacoplan
3. Evidence of rejection on the screening renal allograft biopsy that requires treatment
4. Diagnosis or history of HIV, hepatitis B, or hepatitis C infection or positive serology at screening indicative of infection with any of these viruses
5. Weight more than 100 kg at screening
6. Hypersensitivity to pegcetacoplan or any of the excipients
7. History of meningococcal disease
8. 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
9. 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
10. 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
11. Women who are pregnant, or who are currently breastfeeding
12. Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject’s risk by participating in the study or confound the outcome of the study
13. Evidence of drug or alcohol abuse or dependence, in the opinion of the investigator
14. Known or suspected hereditary fructose intolerance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the proportion of subjects with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan.

Secondary endpoints 7

1. The proportion of subjects with reduction in C3c staining on renal biopsy after 52 weeks of treatment
2. The proportion of subjects with stabilization or improvement in estimated glomerular filtration rate (eGFR), over time
3. The proportion of subjects with stabilization or improvement of serum creatinine concentration over time
4. Changes from baseline biopsy in C3c staining over time
5. Changes and percentage changes from baseline in eGFR and serum creatinine concentration over time
6. Safety: The number and incidence of treatment-emergent adverse events (TEAEs)
7. Safety: The change from baseline in vital signs measurements and clinical laboratory test and ECG results

Investigational products

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

Test 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

Clin. Development and Med. Affairs

Public contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clin. Development and Med. Affairs

Third parties 16

Locations

3 EU/EEA countries · 3 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

Documents 13 files

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

Application history

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