Efgartigimod for Antibody-Mediated Rejection

(Shamrock Trial)

Recruiting at 23 trial locations

Overseen By Sabine Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: argenx

Must be taking: Immunosuppressants

Disqualifiers: T-cell rejection, Pregnancy, others

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

Duration: 48 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called efgartigimod PH20 SC, a type of immunotherapy, to determine its effectiveness for individuals experiencing antibody-mediated rejection after a kidney transplant. The trial aims to assess the safety and efficacy of this treatment when combined with standard medications used to prevent organ rejection. Participants will be divided into groups, with some receiving the new treatment and others receiving a placebo while continuing their usual medications. This study suits those who had a kidney transplant at least six months ago and are experiencing active antibody-mediated rejection. Participants will remain in the study for up to 78 weeks. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

No, you will not have to stop taking your current medications. Participants must stay on their standard background immunosuppression therapy, including tacrolimus, mycophenolate mofetil, and steroids, during the treatment period.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that efgartigimod PH20 SC has undergone safety testing in people. Studies have found that this treatment is generally well-tolerated. While all medications can have side effects, serious ones are rare. Mild reactions might occur at the injection site. This treatment is used alongside standard drugs that help prevent organ rejection after a transplant.

It's important to note that this trial is in an early phase, meaning researchers are still gathering information to fully understand the treatment's safety. However, reaching this stage indicates it has demonstrated a reasonable level of safety in earlier tests. If considering joining the trial, discussing any concerns with a healthcare provider can be helpful. ^{1 2 3 4 5}

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

Unlike the standard treatments for antibody-mediated rejection, which typically involve a combination of immunosuppressants like tacrolimus, mycophenolate mofetil, and steroids, Efgartigimod PH20 SC offers a different approach. Efgartigimod is designed to specifically reduce pathogenic antibodies by targeting the neonatal Fc receptor (FcRn), potentially offering a more precise method of reducing harmful antibodies without broadly suppressing the immune system. Additionally, its subcutaneous (SC) delivery could provide a more convenient and less invasive option compared to traditional intravenous treatments. Researchers are excited about Efgartigimod because it could lead to better outcomes with fewer side effects, offering a novel mechanism that could improve the quality of life for patients.

What evidence suggests that efgartigimod PH20 SC might be an effective treatment for Antibody-Mediated Rejection?

Research shows that efgartigimod can treat conditions related to antibody issues, such as generalized myasthenia gravis and myositis. In individuals with myasthenia gravis, efgartigimod has reduced symptoms and improved muscle strength. This trial will administer efgartigimod to participants in different treatment arms to test its potential in addressing antibody-mediated rejection (AMR) after kidney transplants. Efgartigimod adjusts the immune system by lowering certain antibodies that might cause organ rejection. While specific results for AMR are still being gathered, its success in other conditions suggests potential benefits. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients aged 18-80 with Antibody-Mediated Rejection (AMR) who have had their transplant at least 6 months ago. Participants must be on stable doses of mycophenolate mofetil and tacrolimus, with a low steroid dose for specific periods before the study.

Inclusion Criteria

I have been taking mycophenolate mofetil for at least 20 weeks.

I have been on a stable dose of mycophenolate mofetil and tacrolimus for at least 4 weeks.

I had a kidney transplant more than 6 months ago.

Exclusion Criteria

Confirmed T-cell or mixed rejection at time of the study

Any other medical condition that, in the investigator's opinion, would interfere with the results of the study or put the participant at undue risk

Pregnant or lactating state or intention to become pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Treatment

Participants receive Efgartigimod PH20 SC or placebo subcutaneously while on standard background immunosuppression therapy

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

approximately 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efgartigimod PH20 SC

Trial Overview The trial tests Efgartigimod PH20 SC's safety and effectiveness against AMR in kidney transplant patients. It compares efgartigimod to a placebo, both given by prefilled syringe alongside standard immunosuppression drugs over a treatment period of 48 weeks followed by observation.

How Is the Trial Designed?

Group I: Treatment arm 2 Experimental Treatment 2 Interventions

Participants receiving Efgartigimod PH20 SC on top of optimized standard background immunosuppression therapy (tacrolimus, mycophenolate mofetil, and optionally steroids) up to week 24 followed by placebo PH20 SC on top of optimized standard background immunosuppression therapy from weeks 24 to 48

Group II: Treatment arm 1 Experimental Treatment 1 Intervention

Participants receiving Efgartigimod PH20 SC on top of optimized standard background immunosuppression therapy (tacrolimus, mycophenolate mofetil, and optionally steroids)

Group III: Treatment arm 3 Placebo Group 1 Intervention

Participants receiving Placebo PH20 SC on top of optimized standard background immunosuppression therapy (tacrolimus, mycophenolate mofetil, and optionally steroids)

Efgartigimod PH20 SC is already approved in European Union, United States, Japan, China for the following indications:

Approved in European Union as VYVGART for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in United States as VYVGART Hytrulo for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
• Chronic inflammatory demyelinating polyneuropathy (CIDP)

Approved in Japan as VYVDURA for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in China as Efgartigimod alfa injection (subcutaneous injection) for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

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

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]

Efgartigimod, a human IgG1 antibody, significantly improved symptoms in patients with generalized myasthenia gravis, with 68% of treated patients showing a meaningful response compared to only 30% in the placebo group, indicating strong efficacy.

The treatment was well tolerated, with similar rates of adverse events between efgartigimod and placebo groups, suggesting it is a safe option for patients, with no deaths reported during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Howard, JF., Bril, V., Vu, T., et al.[2022]

Intravenous immunoglobulin (IVIG) combined with rituximab has been shown to effectively reduce anti-HLA antibodies, improving transplantation success rates for highly sensitized patients who were previously considered poor candidates.

The combination therapy also provides a strong anti-inflammatory effect, which is beneficial in treating antibody-mediated rejection, and advancements in detection methods allow for earlier intervention to prevent allograft loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients. Jordan, SC., Peng, A., Vo, AA.[2015]

In a study of 112 endomyocardial biopsies from 25 heart transplant patients, C4d positivity was identified as a key indicator of acute antibody-mediated (humoral) rejection, which can lead to serious complications like graft loss.

The presence of C4d in biopsies was associated with slower recovery in patients, suggesting that humoral rejection can persist even when cellular rejection signs diminish, potentially worsening allograft vasculopathy regardless of the patient's age or time since transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C4d-the witness of humoral rejection. de Gouveia, RH., Vitorino, E., Ramos, S., et al.[2009]

Efgartigimod alfa is the first neonatal Fc receptor antagonist approved for treating generalized myasthenia gravis (gMG), showing significant and rapid improvements in muscle strength and quality of life in a phase 3 trial with a placebo group.

The treatment was generally well tolerated, with most side effects being mild to moderate, indicating a favorable safety profile for patients with gMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. Heo, YA.[2023]

Efgartigimod, a first-in-class neonatal Fc receptor antagonist, received its first approval in the USA in December 2021 for treating generalized myasthenia gravis in adults who are positive for anti-acetylcholine receptor antibodies.

The drug is also being evaluated for other autoimmune diseases and has been approved in Japan for generalized myasthenia gravis patients regardless of antibody status, indicating its potential broad application in autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod: First Approval. Heo, YA.[2022]

Efgartigimod, an FcRn inhibitor, has shown potential in reducing harmful autoantibodies and alleviating symptoms in autoimmune diseases like myasthenia gravis and primary immune thrombocytopenia.

The neonatal crystallizable fragment receptor (FcRn) plays a crucial role in immune regulation by controlling the recycling of IgG antibodies and facilitating antigen presentation, making it a promising target for autoimmune therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roles of FcRn in Antigen-Presenting Cells during Autoimmunity and a Clinical Evaluation of Efgartigimod as an FcRn Blocker. Zhou, Y., Jiang, S.[2023]

Efgartigimod was found to be safe and well-tolerated in a phase 2 study involving 24 patients with generalized myasthenia gravis, with no serious adverse events reported.

The treatment led to a significant reduction in pathogenic IgG autoantibodies and resulted in a rapid and long-lasting improvement in disease symptoms for 75% of patients, suggesting its potential as an effective therapy for myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Howard, JF., Bril, V., Burns, TM., et al.[2020]

In a pilot study involving six pediatric renal transplant recipients with chronic antibody-mediated rejection (CAMR), treatment with high-dose intravenous immunoglobulin (IVIG) and rituximab led to a significant improvement in kidney function, as indicated by an increase in glomerular filtration rate (GFR) after 6 months.

The treatment was well tolerated, suggesting it is a safe option for managing CAMR, and four out of six patients showed improvement or stabilization of their kidney function, highlighting the potential efficacy of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Billing, H., Rieger, S., Ovens, J., et al.[2022]

In a study involving four patients with acute antibody-mediated rejection (ABMR) of kidney transplants, the combination of double filtration plasmapheresis (DFPP) and semi-selective immunoadsorption (IA) showed significant effectiveness in reducing ABMR severity and improving kidney function in early cases.

The results suggest that DFPP + IA can be a valuable rescue treatment for severe ABMR in high-risk patients, particularly when other treatments have failed, although responses may vary in later cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Double Membrane Filtration Immunoadsorption in Severe C1q-Binding Donor-Specific Antibody-Positive Acute Humoral Kidney Allograft Rejection: A Case Series. Russwurm, M., Maier-Giebing, T., Kortus-Goetze, B., et al.[2023]

In a study of 39 renal transplant recipients with antibody-mediated rejection (ABMR), treatment with intravenous immunoglobulin (IVIG) significantly improved renal function compared to those receiving only methylprednisolone (MP).

The improvement in glomerular filtration rate (GFR) for the IVIG group was notable, with a change in slope from -0.72 to -0.03 mL/min/month post-treatment, indicating a positive effect of IVIG on graft function over 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney. Furmańczyk-Zawiska, A., Urbanowicz, A., Perkowska-Ptasińska, A., et al.[2019]

In a study of 43 patients with chronic active antibody-mediated rejection (CAMR), the combination therapy of rituximab and intravenous immunoglobulin (IVIg) showed a 3-year allograft survival rate of 60.5%, with better outcomes in patients with low proteinuria (69.2%) compared to those with high proteinuria (47.1%).

The therapy effectively reduced the decline in kidney function (eGFR) in both groups, particularly in those with low proteinuria, indicating that lower protein levels at treatment are predictive of better allograft survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcome of Rituximab and Intravenous Immunoglobulin Combination Therapy in Kidney Transplant Recipients with Chronic Active Antibody-Mediated Rejection. Ban, TH., Yu, JH., Chung, BH., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06503731

NCT06503731 | A Study to Evaluate the Safety and ... The purpose of this study is to assess the safety, tolerability, and efficacy of efgartigimod PH20 SC given by a prefilled syringe in participants with ...

2. argenx.com argenx.com/news/2025/press-release-3166778

argenx to Highlight Key Data and Breadth of Immunology ... ... Outcomes of Efgartigimod PH20 Sc in Adult Participants with New-Onset Generalized Myasthenia Gravis, AANEM Poster #232. Poster Sessions I & II.

3. amjtransplant.org amjtransplant.org/article/S1600-6135(25)02020-9/fulltext

Trial Design of the Phase 2 Study SHAMROCK Evaluating ... Results: The study will primarily report the safety, tolerability, and efficacy of efgartigimod PH20 SC in adult kidney transplant recipients diagnosed with AMR ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-efgartigimod-for-patients-with-antibody-mediated-rejection-after-kidney-transplant/

Study on Efgartigimod for Patients with Antibody-Mediated ... This clinical study is testing the effectiveness of Efgartigimod in treating patients who have experienced Antibody-Mediated Rejection following a kidney ...

5. argenx.com argenx.com/news/2024/argenx-presents-new-efgartigimod-data-at-eular-2025-highlighting

argenx Presents New Efgartigimod Data at EULAR 2025 ... The data presented at EULAR highlight efgartigimod's potential as a precision therapy for patients living with myositis and Sjogren's disease.

6. argenx.com argenx.com/patients/clinical-trials

Clinical Trials ... Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC Administered by a Prefilled Syringe in Kidney Transplant Recipients with Antibody-Mediated Rejection.

7. allclinicaltrials.com allclinicaltrials.com/study/NCT06503731

Efgartigimod PH20 - A Study to Evaluate the Safety and ... The purpose of this study is to assess the safety, tolerability, and efficacy of efgartigimod PH20 SC given by a prefilled syringe in ...