Pegcetacoplan for Complement 3 Glomerulopathy

(VALE Trial)

Not currently recruiting at 57 trial locations

Overseen By Apellis Clinical Trial Information Line

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Apellis Pharmaceuticals, Inc.

Must be taking: Pegcetacoplan

Disqualifiers: Pregnancy, Breastfeeding, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety and effectiveness of pegcetacoplan for individuals with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN), both kidney conditions. Pegcetacoplan is administered as an injection under the skin twice a week. Individuals who participated in a previous related study, found it beneficial, and continue their treatment for these kidney conditions might be eligible. Participants should have received certain vaccinations and be willing to self-administer the treatment or have a caregiver assist them. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to validating a promising treatment.

Do I need to stop my current medications to join the trial?

The trial requires you to stay on a stable treatment plan for your condition, so you likely won't need to stop your current medications.

Is there any evidence suggesting that pegcetacoplan is likely to be safe for humans?

Research has shown that pegcetacoplan is generally safe for treating C3 glomerulopathy (C3G). Studies have found it well-tolerated in various kidney conditions, including C3G and immune-complex membranoproliferative glomerulonephritis (IC-MPGN). Other research indicates its safety for patients with kidney problems, even post-transplant.

The FDA has approved pegcetacoplan for other conditions, suggesting its safety is well-understood. Overall, current evidence supports its general safety for people, with few side effects reported in trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for C3 glomerulopathy?

Unlike the standard treatments for Complement 3 Glomerulopathy, which often aim to manage symptoms or slow disease progression, Pegcetacoplan offers a novel approach by specifically targeting the complement system. Most current therapies don't directly address the underlying mechanisms of the disease, but Pegcetacoplan is designed to inhibit Complement 3, a key part of the immune response that contributes to kidney damage in this condition. Researchers are excited because this targeted approach has the potential to more effectively halt or even reverse disease progression, offering new hope for patients. Plus, Pegcetacoplan is administered subcutaneously, which is a convenient method that can be done at home, making treatment more accessible and less burdensome for patients.

What evidence suggests that pegcetacoplan might be an effective treatment for C3 glomerulopathy?

Research has shown that pegcetacoplan, which participants in this trial will receive, may help treat certain kidney conditions, such as C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN). In earlier studies, pegcetacoplan reduced excess protein in urine by 68% at week 26 compared to a placebo, and this benefit persisted over time. It also increased average levels of a protein called C3 in the blood, which can help lower harmful activity linked to C3G. About one-third of patients experienced a complete reduction in excess urine protein, and this improvement lasted for a year. These findings suggest pegcetacoplan could effectively manage these kidney conditions. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients who have certain kidney diseases like C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis and were part of a previous study (APL2-C3G-310). They should have seen benefits from the drug pegcetacoplan, be vaccinated against specific infections, and agree to use contraception. It's not open to new patients; only those continuing from the prior study.

Inclusion Criteria

Completed participation in Study APL2-C3G-310 through the week 52 visit requirements

I can self-administer my medication or have someone to help me.

I benefited from pegcetacoplan treatment in a past trial, according to my doctor.

Exclusion Criteria

I am not pregnant, planning to become pregnant, or breastfeeding during the study and for 90 days after.

Inability or unwillingness to cooperate with the requirements of the protocol

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegcetacoplan administered subcutaneously twice weekly

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Continuation of treatment to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pegcetacoplan

Trial Overview The trial is testing the long-term safety and effectiveness of a medication called pegcetacoplan in people with specific kidney conditions. This extension study follows up on earlier research where participants already received this treatment for about one year.

How Is the Trial Designed?

Group I: Pegcetacoplan administered subcutaneously Experimental Treatment 1 Intervention

Pegcetacoplan administered subcutaneously twice weekly according to protocol defined dosing regimen

Pegcetacoplan is already approved in United States, European Union for the following indications:

Approved in United States as Empaveli for:

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Approved in European Union as Aspaveli for:

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Apellis Pharmaceuticals, Inc.

Lead Sponsor

Trials

26

Recruited

4,300+

Published Research Related to This Trial

Iptacopan, a selective inhibitor of factor B in the alternative complement pathway, is being evaluated in a Phase III study involving 68 adults with complement 3 glomerulopathy (C3G) to assess its efficacy and safety in reducing proteinuria and improving kidney function.

The study aims to show that iptacopan can significantly reduce protein levels in urine (measured by urine protein:creatinine ratio) compared to a placebo, potentially offering a new treatment option for patients with this rare kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. Bomback, AS., Kavanagh, D., Vivarelli, M., et al.[2022]

C3 glomerulopathy is a complex kidney disease affecting a diverse group of patients, with a mean diagnosis age of 40.4 years, and is characterized by significant proteinuria and hematuria, indicating kidney damage.

The disease shows a variable response to treatment, with most patients receiving corticosteroids and immunosuppressive drugs; however, 9.2% of patients without monoclonal immunoglobulin progressed to end-stage renal disease within a median follow-up of 22.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C3 Glomerulopathy: Ten Years' Experience at Mayo Clinic. Ravindran, A., Fervenza, FC., Smith, RJH., et al.[2020]

Avacopan, a C5aR antagonist, was safely administered to a child with C3 glomerulonephritis (C3GN) in a Phase 2 clinical trial, demonstrating good tolerability and safety.

The patient was able to discontinue the use of mycophenolate mofetil (MMF) while maintaining remission from C3GN, suggesting that avacopan may be an effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment with avacopan (CCX168) in a pediatric patient with C3 glomerulonephritis. Zotta, F., Diomedi-Camassei, F., Gargiulo, A., et al.[2023]

Citations

1. investors.apellis.com investors.apellis.com/news-releases/news-release-details/new-one-year-data-reinforcing-robust-and-sustained-efficacy

Release Details Complete proteinuria remission achieved in one-third of patients and sustained through one year: One-third of EMPAVELI-treated patients achieved ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10658235/

Clinical Safety and Efficacy of Pegcetacoplan in a Phase 2 ... Pegcetacoplan increased mean serum C3, providing evidence that pegcetacoplan reduced C3 activation in patients with C3G with aberrant complement regulation.

3. clinicaltrials.gov clinicaltrials.gov/study/nct05067127

nct05067127 | Phase III Study Assessing the Efficacy and ... This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 ...

4. kireports.org kireports.org/article/S2468-0249(24)01961-2/fulltext

Efficacy and Safety of Pegcetacoplan in Kidney Transplant ... At week 12, 5 of 10 pegcetacoplan-treated patients (50%) achieved ≥2 orders of magnitude (OOM) reduction in C3 staining (4 of these 5 had 0 ...

5. checkrare.com checkrare.com/new-data-on-pegcetacoplan-in-patients-with-c3g-and-ic-mpgn/

New Data on Pegcetacoplan in Patients With C3G and IC- ... Pegcetacoplan demonstrated a statistically significant proteinuria reduction of 68% at week 26 versus placebo. This reduction was sustained at ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924019612

Efficacy and Safety of Pegcetacoplan in Kidney Transplant ... NOBLE demonstrated efficacy, safety, and tolerability of pegcetacoplan for patients with posttransplant recurrent C3G and primary IC-MPGN.

7. investors.apellis.com investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and

FDA Approves Apellis' EMPAVELI® (pegcetacoplan) as ... In the Phase 3 VALIANT study, EMPAVELI demonstrated an unprecedented 68% reduction in proteinuria, stabilization of kidney function, and ...

8. plainlanguagesummaries.com plainlanguagesummaries.com/discovery-study-findings-on-pegcetacoplan-for-treating-rare-kidney-diseases-linked-to-complement-system-dysfunction-plain-language-summary/

DISCOVERY study findings on pegcetacoplan for treating ... This summary describes the DISCOVERY study, a phase 2 clinical trial evaluating pegcetacoplan in patients with complement 3 glomerulopathy ...