Efgartigimod for Sjogren's Syndrome

(Unity Trial)

Recruiting at 4 trial locations

Overseen By Sabine Coppieters, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: argenx

Must not be taking: Cyclophosphamide, Anti-CD20, Anti-CD19

Disqualifiers: Secondary Sjögren's, Active fibromyalgia, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The main purpose of the proposed study is to evaluate the efficacy of efgartigimod PH20 SC in patients with moderate-to-severe Primary Sjögren's Disease (pSjD). The study consists of a double-blinded placebo-controlled treatment period and an open-label treatment period. The maximum study duration for participants in both study parts is approximately 105 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used cyclophosphamide within 24 weeks before screening or received anti-CD20 or anti-CD19 antibodies within 6 months before screening.

How does the drug Efgartigimod differ from other treatments for Sjogren's Syndrome?

Efgartigimod is unique because it is designed to modulate the immune system by targeting and reducing specific antibodies, which is different from other treatments that focus on reducing inflammation or increasing glandular secretions. This approach may offer a novel way to manage the autoimmune aspects of Sjogren's Syndrome. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with moderate-to-severe Primary Sjögren's Disease who meet specific criteria, including a clinESSDAI score of at least 6 and positive Anti-Ro/SS-A. Participants must have some natural salivary flow and consent to the study.

Inclusion Criteria

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

I meet the specific criteria for a type of joint disease, have active symptoms, tested positive for Anti-Ro/SS-A, and have a certain level of salivary flow.

Exclusion Criteria

I have Sjögren's syndrome as a result of another autoimmune condition.

Active fibromyalgia which is not adequately controlled in the judgment of the investigator, or participant is receiving fibromyalgia treatment that has not been stable treatment for at least 12 weeks before screening

I have used cyclophosphamide within the last 24 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blinded Treatment

Participants receive either efgartigimod PH20 SC or placebo during the double-blinded treatment period

48 weeks

Open-label Treatment

Participants receive efgartigimod PH20 SC during the open-label treatment period

Up to 57 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Efgartigimod (Monoclonal Antibodies)

Trial Overview The trial is testing Efgartigimod PH20 SC against a placebo in patients with Primary Sjögren's Syndrome. It includes a double-blind period where neither doctors nor patients know who gets what, followed by an open-label phase for up to 105 weeks.

Participant Groups

Group I: Open-label treatment period Experimental Treatment 1 Intervention

Participants receiving efgartigimod PH20 SC during the open-label treatment period

Group II: Double-blinded treatment period: Efgartigimod PH20 SC Experimental Treatment 1 Intervention

Participants receiving efgartigimod PH20 SC during the double-blinded treatment period

Group III: Double-blinded treatment period: Placebo PH20 SC Placebo Group 1 Intervention

Participants receiving placebo PH20 SC during the double-blinded treatment period

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

Cenerimod, a selective sphingosine-1-phosphate receptor 1 modulator, effectively reduced immune cell infiltration and inflammation in salivary glands in two mouse models of Sjögren's syndrome, suggesting its potential to improve gland function.

In both models, cenerimod treatment led to decreased autoantibody production and disaggregation of ectopic lymphoid structures, indicating a reduction in the autoimmune response associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren's syndrome. Gerossier, E., Nayar, S., Froidevaux, S., et al.[2021]

In an animal model of Sjögren's Syndrome, Fingolimod effectively reduced the number of circulating T and B cells, which are involved in the autoimmune response, suggesting a potential mechanism for managing the disease.

Fingolimod treatment led to increased salivary output and decreased salivary gland infiltrates, indicating its efficacy in alleviating symptoms associated with Sjögren's Syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjögren's model. Cohen, PL., McCulloch, A.[2023]

Sjögren's syndrome is often underdiagnosed and undertreated, but recent classification criteria have improved clinical management and research efforts.

The disease is characterized by hypofunction of glandular epithelial cells rather than their destruction, which is crucial for understanding its pathogenesis and guiding treatment options like pilocarpine and hydroxychloroquine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sjögren's syndrome. Venables, PJ.[2005]

The combination of iguratimod (IGU) and methylprednisolone (MP) significantly reduces markers of inflammation and disease activity in primary Sjögren's syndrome (pSS), including erythrocyte sedimentation rate (ESR) and immunoglobulin levels, based on a meta-analysis of clinical studies.

This treatment combination does not increase the risk of adverse events compared to the standard treatment of hydroxychloroquine (HCQ) and MP, suggesting that IGU and MP may be a safe and effective option for managing pSS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iguratimod combined with methylprednisolone for primary Sjögren's syndrome: a meta-analysis and trial sequential analysis. Hu, G., Yu, YF., Yin, S., et al.[2023]

Iguratimod significantly reduces symptoms in patients with Primary Sjogren's syndrome, as evidenced by lower scores in ESSPRI and ESSDAI, and improved Schirmer's test results, based on a meta-analysis of 29 RCTs involving 2258 participants.

The treatment does not appear to increase the risk of adverse events, which were mostly mild, such as gastrointestinal discomfort and rash, suggesting that Iguratimod is a safe option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of 19 Randomized Controlled Trials of Iguratimod Combined With Other Therapies for Sjogren's Syndrome. Zeng, L., He, Q., Yang, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren's syndrome. [2021]

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

Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjögren's model. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Sjögren's syndrome. [2005]

4. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iguratimod combined with methylprednisolone for primary Sjögren's syndrome: a meta-analysis and trial sequential analysis. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of 19 Randomized Controlled Trials of Iguratimod Combined With Other Therapies for Sjogren's Syndrome. [2022]