Efgartigimod for Immune Thrombocytopenic Purpura

(advance NEXT Trial)

Recruiting at 99 trial locations

Overseen By Sabine Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: argenx

Disqualifiers: Autoimmune disease, Secondary ITP, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the efficacy and safety of efgartigimod, administered via IV, for individuals with primary immune thrombocytopenia (ITP), a condition where the immune system attacks and reduces blood platelets, causing easy bruising and bleeding. Participants will initially receive either efgartigimod or a placebo (a harmless substance with no treatment effect) for up to 24 weeks, followed by efgartigimod for up to two years. Suitable candidates for this trial have had ITP for over a year, have low platelet counts, and have previously tried at least one treatment, such as corticosteroids or IVIg, without sufficient success. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves participants with prior ITP treatments, it might be possible to continue some medications. Please consult with the trial coordinators for specific guidance.

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

Research has shown that efgartigimod is generally safe for people. In studies involving individuals with chronic immune thrombocytopenia (ITP), many participants experienced an increase in platelet counts, aiding blood clotting. This suggests the treatment is working as intended.

Regarding safety, these studies reported no unexpected or severe side effects. Most participants did not encounter serious issues. Any side effects were typically mild, such as headaches or reactions at the injection site.

As this treatment is in the later stages of clinical trials, substantial evidence already supports its safety for humans. This level of testing is usually reached when earlier studies have indicated that the treatment is likely safe and effective. ^{1 2 3 4 5}

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

Unlike the standard treatments for Immune Thrombocytopenic Purpura (ITP), which often include corticosteroids, immunoglobulins, or splenectomy, efgartigimod offers a novel approach by targeting the neonatal Fc receptor (FcRn). This mechanism reduces the levels of disease-causing antibodies by blocking their recycling, potentially leading to a more effective and sustained increase in platelet counts. Researchers are excited about efgartigimod because it could offer a targeted treatment with fewer side effects and improved quality of life for patients, distinguishing it from more traditional, less specific therapies. Additionally, the option to administer it intravenously allows for controlled and direct delivery of the treatment.

What evidence suggests that efgartigimod might be an effective treatment for immune thrombocytopenia?

Research has shown that efgartigimod holds promise for treating primary immune thrombocytopenia (ITP). In this trial, participants will receive either efgartigimod or a placebo during the double-blinded treatment period. Studies found that patients who received efgartigimod maintained more stable platelet counts compared to those who received a placebo. As a result, more patients kept healthy platelet levels, reducing the risk of bleeding. The treatment targets a protein in the immune system, preventing the breakdown of platelets. These positive results suggest efgartigimod could effectively manage ITP. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with primary immune thrombocytopenia (ITP) who have low platelet counts and haven't responded well to previous treatments like steroids or immunoglobulins. Participants must be at least 18 years old, legally able to consent, and have had ITP for over a year.

Inclusion Criteria

My platelet count is below 30 x 10^9/L.

I have had immune thrombocytopenia for over a year.

I have been treated for ITP with steroids, IVIg, anti-D, TPO-RAs, or rituximab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Double-Blinded Treatment Period (DBTP)

Participants are randomized to receive either efgartigimod IV or placebo IV

up to 24 weeks

Open-Label Treatment Period 1 (OLTP1)

All participants receive efgartigimod IV

52 weeks

Open-Label Treatment Period 2 (OLTP2)

Participants may continue to receive efgartigimod IV

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment while off study drug

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efgartigimod

Trial Overview

The study tests the effectiveness and safety of Efgartigimod IV compared to a placebo in treating ITP. Participants are randomly assigned to receive either the drug or placebo during an initial double-blind phase, followed by open-label phases where all get Efgartigimod IV.

How Is the Trial Designed?

Group I: Placebo IV Experimental Treatment 2 Interventions

Participants receiving placebo IV during the double-blinded treatment period and receiving efgartigimod IV during the open-label treatment period(s)

Group II: Efgartigimod IV Experimental Treatment 1 Intervention

Participants receiving efgartigimod IV during the double-blinded treatment period and the open-label treatment period(s)

Efgartigimod is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

Approved in United States as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Approved in Canada as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

Approved in Japan as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

Who Is Running the Clinical Trial?

argenx

Lead Sponsor

Trials

76

Recruited

11,500+

Tim Van Hauwermeiren

argenx

Chief Executive Officer since 2008

B.Sc. and M.Sc. in Bioengineering from Ghent University, Executive MBA from The Vlerick School of Management

Dr. Peter Ulrichts

argenx

Chief Medical Officer since 2023

MD from Maastricht University, PhD in Molecular Immunology from Maastricht University

Published Research Related to This Trial

In a Phase 2 study involving 38 patients with primary immune thrombocytopenia (ITP), efgartigimod, an FcRn antagonist, was well tolerated and showed a favorable safety profile, consistent with earlier Phase 1 data.

Efgartigimod treatment led to a significant reduction in total IgG levels and clinically relevant increases in platelet counts, with 46% of patients achieving a platelet count of ≥50 × 10^9/L compared to 25% on placebo, indicating its potential as a novel treatment for ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. Newland, AC., Sánchez-González, B., Rejtő, L., et al.[2021]

Intravenous immunoglobulins (IVIgG) have been generalized for use in treating idiopathic thrombocytopenic purpura (ITP), showing promise in improving patient outcomes.

Preliminary data from two studies involving 42 patients indicate that a new non-modified IVIgG formulation may also be effective in treating ITP, suggesting potential advancements in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new intravenous immunoglobulin in adult and childhood idiopathic thrombocytopenic purpura: a review. Rousell, RH.[2019]

In a phase 3 study involving 131 adults with chronic primary immune thrombocytopenia, efgartigimod significantly improved sustained platelet count responses compared to placebo, with 22% of patients achieving the primary endpoint versus 5% in the placebo group.

Efgartigimod was well tolerated, with most adverse events being mild to moderate, indicating a favorable safety profile for patients who had previously undergone multiple treatments for their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Broome, CM., McDonald, V., Miyakawa, Y., et al.[2023]

In a study of 35 patients with idiopathic thrombocytopenic purpura (ITP), Gammaplex (5% IVIg) was found to be effective, with 83% of patients achieving a significant increase in platelet count to ≥ 50 × 10(9)/L within 9 days.

Gammaplex was well-tolerated, with a median response duration of 10 days and no unexpected adverse events, although some patients experienced common side effects like headache and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (ClinicalTrials.gov--NCT00504075). Dash, CH., Gillanders, KR., Stratford Bobbitt, ME., et al.[2022]

In a study of 64 patients with chronic immune thrombocytopenic purpura (ITP), 81.3% achieved a significant increase in platelet counts after receiving 10% intravenous immunoglobulin (IVIG) treatment, indicating its efficacy.

The treatment was found to be safe, with 92.2% of patients experiencing only mild to moderate adverse events, suggesting a favorable safety profile for both adults and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravenous immunoglobulin (Flebogamma® 10% DIF) in patients with immune thrombocytopenic purpura. Apte, S., Navarro-Puerto, J., Damodar, S., et al.[2019]

Efgartigimod is a promising new treatment for primary immune thrombocytopenia (ITP) that works by binding to the neonatal Fc receptor (FcRn), which leads to increased degradation of IgG antibodies that cause platelet destruction.

This therapy offers a novel mechanism of action compared to existing treatments, potentially providing an effective option for patients who may not respond well to traditional therapies like corticosteroids or IVIgG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod alfa for the treatment of primary immune thrombocytopenia. Broome, C.[2023]

High-dose IVIgG can induce partial or complete responses in about 10-15% of patients with immune thrombocytopenic purpura (ITP) who do not respond to corticosteroids or splenectomy, likely by blocking Fc receptors for IgG (FcgammaR).

The humanized monoclonal antibody H22 effectively blocks FcgammaRI-mediated phagocytosis and down-modulates FcgammaRI expression on monocytes, making it a promising candidate for further research in ITP treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcgammaRI), blocks phagocytosis, and modulates receptor expression. Wallace, PK., Keler, T., Coleman, K., et al.[2019]

Citations

1.

argenx.com

argenx.com/news/2022/argenx-announces-positive-phase-3-data-advance-trial-vyvgartr-efgartigimod-alfa-fcab-adults

argenx Announces Positive Phase 3 Data from ADVANCE ...

ADVANCE met its primary endpoint demonstrating that a higher proportion of chronic ITP patients receiving VYVGART achieved a sustained platelet count response ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10176552/

Efgartigimod alfa for the treatment of primary immune ...

This article will briefly discuss the pathophysiology of ITP, current treatments, and the data available on efgartigimod in ITP. Keywords: ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06544499

NCT06544499 | A Study to Assess the Efficacy and Safety ...

The main purpose of this study is to look at the effect (efficacy) and safety of efgartigimod IV in participants with primary immune thrombocytopenia (ITP).

4.

zailab.gcs-web.com

zailab.gcs-web.com/news-releases/news-release-details/zai-lab-partner-argenx-announces-positive-phase-3-data-advance

Zai Lab Partner argenx Announces Positive Phase 3 Data ...

Study met primary endpoint, demonstrating a higher proportion of sustained platelet response with VYVGART treatment compared to placebo ...

5.

targetedonc.com

targetedonc.com/view/primary-end-point-met-in-the-advance-trial-for-patients-with-thrombocytopenia

Primary End Point Met in the ADVANCE Trial for Patients ...

The primary end point has been met in the phase 3 ADVANCE trial which evaluated the efficacy and safety of efgartigimod alfa-fcab in patients ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37778358/

Efficacy and safety of the neonatal Fc receptor inhibitor ...

Efgartigimod significantly increased sustained platelet count responses compared with placebo in patients with chronic immune thrombocytopenia.

7.

yalemedicine.org

yalemedicine.org/clinical-trials/argx-113-2402-a-study-to-assess-the-efficacy-and-safety-of-efgartigimod-iv-in-adult-participants-wi

A Phase 3, Multicenter, Randomized, Double-Blinded, ...

The main purpose of this study is to look at the effect (efficacy) and safety of efgartigimod IV in participants with primary immune ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04225156

NCT04225156 | A Long-term Study to Assess the Safety ...

This is an open-label long-term multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in adult patients with primary ITP. Official Title. A ...