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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug efgartigimod for treating Stiff Person Syndrome?

Efgartigimod has shown promising results in improving symptoms in patients with both Stiff Person Syndrome and myasthenia gravis, as reported in a study where patients experienced symptom improvement after treatment. Additionally, efgartigimod is effective in reducing disease burden and improving muscle strength in patients with generalized myasthenia gravis, suggesting potential benefits for similar autoimmune conditions like Stiff Person Syndrome. ^{1 2 3 4 5}

How is the drug efgartigimod different from other treatments for stiff person syndrome?

Efgartigimod is unique because it targets the neonatal Fc receptor, reducing levels of harmful antibodies, and has shown promising results in improving symptoms of stiff person syndrome, unlike traditional treatments whose effectiveness is not well established. ^{1 2 6 7 8}

What is the purpose of this trial?

The goal of this clinical trial is to examine the proportion of patients with stiff person syndrome with no worsening in stiffness and/or spasms while on efgartigimod-hyaluronidase (EFD) when compared to their current treatment. The main questions it aims to answer are: * proportion of patients with stiff person syndrome with no worsening in DSI and HSS scores * whether there are changes in laboratory values, vital signs, electrocardiogram, or depression, and suicide risk during the trial, as well as the incidence of any adverse events. Participants will come to the clinic up to 18 times and have up to 5 phone call visits during the course of the trial. During these visits a variety of measures will be collected, including blood samples, neurological and physical exams, patient reported outcomes on stiffness, spasms, depression, and suicide risk.

Research Team

Tuan Vu, MD

Principal Investigator

University of South Florida

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. [2023]

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

Effect of treatment with intravenous immunoglobulin on quality of life in patients with stiff-person syndrome. [2015]

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

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats. [2021]

5. England 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. [2022]

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

High-dose intravenous immune globulin for stiff-person syndrome. [2022]

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

Stiff-person syndrome: insights into a complex autoimmune disorder. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Successful treatment with rituximab in a refractory Stiff-person syndrome]. [2015]