A Study of the Safety and Effectiveness of Efgartigimod in Patients With Primary Sjögren's Syndrome (pSS)

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of human FcRn blocking therapy with efgartigimod compared to placebo, in participants with pSS.

Detailed Description
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Primary Sjogren Syndrome (pSS) is an autoimmune disease with still unmet treatment needs. Efgartigimod, a human FcRn antagonist, has the potential to successfully treat pSS and improve disease manifestations by the reduction of IgG autoantibodies and immune complexes in pSS. The study design is randomized, double-blinded, and placebo-controlled to evaluate the effect of efgartigimod administered as an IV infusion compared to placebo. The study consists of a treatment period when all participants will receive infusions of IP/placebo for 24 weeks. At the end of the randomized treatment period, eligible participants may roll over to an OLE study or remain in this study through the end of the 56-day follow-up period.

Official Title
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A Phase 2, Randomized, Placebo-controlled, Parallel-group, Double-blinded, proof-of Concept Study to Evaluate the Safety and Efficacy of Intravenous Efgartigimod in Adult Participants With Primary Sjögren's Syndrome

Conditions
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Primary Sjögren's Syndrome

Intervention / Treatment
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* Biological: Efgartigimod
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is at least the legal age of consent for clinical trials when signing the informed consent form Is capable of providing signed informed consent and complying with protocol requirements Agrees to use contraceptive measures consistent with local regulations and measures described in the protocol Meets the following criteria at screening: ACR/EULAR 2016 pSS who met criteria ≤7 years before screening; ESSDAI ≥5; Anti-Ro/SS-A positive; Residual salivary flow (UWSF rate >0 and/or SWSF rate >0.10) Exclusion Criteria: Known autoimmune disease or any medical condition that, in the investigator's judgment,would interfere with an accurate assessment of clinical symptoms of pSS or puts the participant at undue risk History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Adequately treated participants with the following cancers may be included at any time: Basal cell or squamous cell skin cancer; Carcinoma in situ of the cervix; Carcinoma in situ of the breast; Incidental histological finding of prostate cancer (TNM stage T1a or T1b) Clinically significant uncontrolled active acute or chronic bacterial, viral, or fungal infection Positive serum test at screening for an active infection with any of the following: HBV that is indicative of an acute or chronic infection, unless associated with a negative HBsAg or negative HBV DNA test; HCV based on HCV antibody assay unless a negative RNA test is available; HIV based on test results of a CD4 count of <200 cells/mm3 that are associated with an AIDS-defining condition, HIV based on test results of a CD4 count of >200 cells/mm3 not adequately treated with antiviral therapy Clinically significant disease, recent major surgery (within 3 months of screening), or intention to have surgery during the study; or any other medical condition that, in the investigator's opinion, would confound the results of the study or put the participant at undue risk Immunoglobulin G (IgG) levels cannot be below a certain threshold ( 4g/L) Positive covid test at study start Some of the medications such as vaccines with live components or medicines that may be prescribed cannot be taken either shortly before or during this study Current participation in another interventional clinical study or previously participation in an efgartigimod clinical study and treatment with ≥1 dose of IMP Known hypersensitivity to IMP or 1 of its excipients History (within 12 months of screening) of current alcohol, drug, or medication abuse as assessed by the investigator Pregnant or lactating state or intention to become pregnant during the study Secondary Sjögren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition is the primary diagnosis Chinese traditional medicine with known immunomodulatory action

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efgartigimod IV arm<br>patients receiving infusions of Efgartigimod IV | Biological: Efgartigimod<br>* Patients receiving efgartigimod infusions<br>|
| Placebo Comparator: Placebo arm<br>patients receiving infusions of placebo IV | Biological: Placebo<br>* Patients receiving placebo infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of CRESS responders on ≥3 of 5 items at week 24 | The 5 items are Systemic disease activity: clinESSDAI; Patient-reported symptoms: ESSPRI; Tear gland function: Schirmer's test and OSS; Salivary gland function: UWSF rate and SGUS; Serology (serum IgG and/or RF) | up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the relative counts of lymphocytic infiltrate (stained for CD45) at week24 |  | up to 24 weeks | 
| Change in B/B+T cell ratio at week 24 |  | up to 24 weeks | 
| Incidence and severity of TEAEs, AESIs, and SAEs by SOC and PT | To evaluate the safety of efgartigimod IV compared to placebo in participants with pSS | up to 35 weeks | 
| Clinically significant changes in vital sign measurements | weight in kg, Systolic Blood Pressure in mmHg, Diastolic Blood Pressure in mmHg, pulse in bpm | Up to 35 weeks | 
| Clinically significant changes in ECG results | Heart Rate in bpm, QRS in ms, PR in ms, QTc in ms | Up to 35 weeks | 
| Clinically significant changes in clinical laboratory safety evaluations | Chemistry, Haematology, HbA1C in %, Urinalysis, beta-hCG mUI/mL | Up to 35 weeks | 
| Proportion of participants with minimal clinically important improvement in ESSDAI: improvement of ≥3 points in ESSDAI score at week 24 |  | up to 24 weeks | 
| Proportion of participants with low disease activity: ESSDAI score of <5 at week 24 |  | up to 24 weeks | 
| Proportion of participants with minimal clinically important improvement in clinESSDAI: improvement of ≥3 points in clinESSDAI score at week 24 |  | up to 24 weeks | 
| Proportion of participants with low disease activity: clinESSDAI score of <5 at week 24 |  | up to 24 weeks | 
| Proportion of participants with minimal clinically important improvement in ESSPRI: decrease of 1 point or ≥15% at week 24 |  | up to 24 weeks | 
| Change in ESSDAI score at week 24 |  | up to 24 weeks | 
| Change in clinESSDAI score at week 24 |  | up to 24 weeks | 
| Change in ESSPRI score at week 24 |  | up to 24 weeks | 
| Proportion of participants with STAR score of ≥5 at week 24 |  | up to 24 weeks |