Efgartigimod for Immune Thrombocytopenic Purpura

(advance NEXT Trial)

Recruiting at6 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: argenx

Disqualifiers: Autoimmune disease, Secondary ITP, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

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). After an up to 2 weeks screening period, eligible participants will be randomized in a 2:1 ratio to receive either efgartigimod IV or placebo IV, respectively during the double-blinded treatment period (DBTP). At the end of the treatment period (up to 24 weeks), all participants will receive efgartigimod IV during the first 52-week open-label treatment period (OLTP1). At the end of the first OLTP1, participants may begin a second 52-week OLTP2. After the OLTP2, the participants will enter a follow-up period (approximately 8 weeks) while off study drug. The participants will be in the study for up to 138 weeks.

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.

What data supports the effectiveness of the drug Efgartigimod for treating immune thrombocytopenic purpura?

Research shows that Efgartigimod, a drug that reduces harmful antibodies in the blood, helped increase platelet counts in patients with immune thrombocytopenic purpura (ITP). In a study, 46% of patients receiving Efgartigimod achieved a significant increase in platelet counts compared to 25% of those on a placebo, indicating its potential effectiveness in treating ITP. ^{1 2 3 4 5}

Is efgartigimod safe for humans?

Efgartigimod has been shown to be well tolerated and has a favorable safety profile in studies with patients having immune thrombocytopenic purpura (ITP). ^{1 2 3 6 7}

How is the drug Efgartigimod different from other treatments for immune thrombocytopenic purpura?

Efgartigimod is unique because it targets the neonatal Fc receptor (FcRn) to reduce levels of IgG antibodies, which are involved in the destruction of platelets in immune thrombocytopenic purpura. This mechanism is different from other treatments like corticosteroids or IVIgG, which do not specifically target FcRn. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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

I am at least 18 years old and legally able to consent.

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

I have had immune thrombocytopenia for over a year.

Trial Timeline

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

Treatment Details

Interventions

• Efgartigimod (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcgammaRI), blocks phagocytosis, and modulates receptor expression. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (ClinicalTrials.gov--NCT00504075). [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravenous immunoglobulin (Flebogamma® 10% DIF) in patients with immune thrombocytopenic purpura. [2019]