Efgartigimod for Stiff Person Syndrome

(ESPS Trial)

Overseen By Jessica D Shaw, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of South Florida

Must be taking: Antispasmodics

Must not be taking: Rituximab, IVIG, PLEX

Disqualifiers: Type 1 DM, Cancer, Infections, others

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

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: 18

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests efgartigimod, a new treatment for people with stiff person syndrome, a condition causing severe muscle stiffness and spasms. The main goal is to determine if this treatment can prevent symptom worsening compared to current treatments. It also examines changes in lab results, heart health, or mood during the trial. Individuals with unexplained muscle stiffness and spasms, along with certain antibodies, might be suitable for this study. Participants will attend regular clinic visits for symptom and health monitoring. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that your dosage of antispasmodics (muscle relaxants) has been stable for at least two months before joining. If you are taking rituximab, you must not have used it within six months before the trial.

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

Research has shown that efgartigimod has been tested for safety in other conditions. In past studies, it was generally safe for people, with most participants tolerating it well.

Common side effects of efgartigimod include injection site reactions, headaches, and infections, which were usually mild or moderate.

This treatment is already FDA-approved for other uses, indicating its safety is well-understood in those cases. However, since it is being tested for stiff person syndrome, monitoring for new side effects is important.

Participants should discuss the possible risks and benefits with their doctor before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stiff person syndrome?

Most treatments for Stiff Person Syndrome (SPS) focus on reducing symptoms with medications like benzodiazepines and muscle relaxants. But efgartigimod works differently by targeting the immune system. It is designed to reduce the levels of harmful antibodies in the body, specifically the GAD65-antibodies associated with SPS. This approach could potentially offer a more targeted and effective treatment, with fewer side effects compared to the broader immune suppression strategies currently used. Researchers are excited about efgartigimod because it may provide relief for patients who have not responded well to existing therapies.

What evidence suggests that efgartigimod might be an effective treatment for stiff person syndrome?

Research has shown that efgartigimod, a treatment targeting a specific protein in the body, holds potential for treating autoimmune conditions. It has proven effective for individuals with generalized myasthenia gravis (gMG), an autoimmune disease causing muscle weakness. This treatment reduces harmful antibody levels in the body. In this trial, participants with GAD65-antibody positive stiff person syndrome will receive subcutaneous Efgartigimod-hyaluronidase (EFG) to assess its potential in managing symptoms like stiffness and spasms. Although no direct evidence exists yet for its use in stiff person syndrome, its mechanism in similar conditions suggests it might help. ^{1 5 6 7 8}

Who Is on the Research Team?

Tuan Vu, MD

Principal Investigator

University of South Florida

Are You a Good Fit for This Trial?

This trial is for patients with stiff person syndrome. Participants should be able to visit the clinic up to 18 times and handle phone call visits. The study excludes those who don't meet specific health criteria, but details on these are not provided.

Inclusion Criteria

My blood (or CSF) tests positive for anti-GAD antibodies.

DSI and HHS must be >=2 (to allow for detection of improvement)

Women with children bearing potential must be willing to use highly effective contraception method during and for a minimum of 90 days after the last dose of IP

Exclusion Criteria

I have had a solid organ or bone marrow transplant.

I have not taken rituximab in the last 6 months.

I have not had IVIG or PLEX treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous Efgartigimod-hyaluronidase (EFG) for 13 weeks

13 weeks

18 visits (in-person), 5 visits (phone call)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efgartigimod

Trial Overview The trial tests efgartigimod's effectiveness in preventing worsening of stiffness and spasms in stiff person syndrome compared to current treatments. It measures changes in symptoms, lab values, vital signs, ECGs, depression, and suicide risk.

How Is the Trial Designed?

Group I: subcutaneous Efgartigimod-hyaluronidase (EFG) Experimental Treatment 1 Intervention

Participants with GAD65-antibody positive SPS will be given subcutaneous Efgartigimod-hyaluronidase (EFG).

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?

University of South Florida

Lead Sponsor

Trials

433

Recruited

198,000+

Published Research Related to This Trial

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]

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 new treatment that reduces pathogenic IgG autoantibodies, showed promising results in three patients with both stiff-person syndrome (SPS) and myasthenia gravis (MG) over a 12-week treatment period, leading to symptom improvement.

This study suggests that efgartigimod could be a potential therapy for SPS and other autoimmune neurological disorders, as it demonstrated efficacy in alleviating symptoms associated with both conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. Di Stefano, V., Alonge, P., Rini, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10769952/

the role of FcRn-targeting therapies in stiff-person syndrome Efgartigimod, a new neonatal Fc receptor (FcRn) blocker, is a human IgG1 antibody Fc fragment engineered with increased affinity for FcRn binding.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06528392

Efgartigimod for Stiff Person Syndrome (ESPS) There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

3. 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.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761195Orig1s000IntegratedR.pdf

761195Orig1s000 - accessdata.fda.gov confirmatory evidence that provides substantial evidence of effectiveness of efgartigimod in patients with gMG who are AChR antibody positive.

5. ema.europa.eu ema.europa.eu/en/documents/variation-report/vyvgart-h-c-005849-ii-0020-epar-assessment-report-variation_en.pdf

Vyvgart, INN: efgartigimod alfa - EMA Table 39: Summary of Efficacy for trial ARGX-113-1802 Stage A and B ... Long-term efficacy results from OLE phase (ARGX-113-1902). aINCAT ...

6. argenx.com argenx.com/content/dam/argenx-corp/products/vyvgart-prescribing-information.pdf

VYVGART prescribing information The safety of immunization with live vaccines and the immune response to vaccination during treatment with VYVGART are unknown. Because VYVGART causes a ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761195s004,761304s003lbl.pdf

VYVGART® (efgartigimod alfa-fcab) injection, for intravenous ... The safety of immunization with live vaccines and the immune response to vaccination during treatment with VYVGART are unknown. Because VYVGART causes a ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/vyvgart-epar-product-information_en.pdf

Vyvgart, INN: efgartigimod alfa - European Medicines Agency 5.3 Preclinical safety data. Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology and repeated dose ...