E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sjögren’s Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Primary Sjögren’s Syndrome |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042846 |
E.1.2 | Term | Syndrome Sjogren's |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of efgartigimod IV compared to placebo on CRESS |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of efgartigimod IV compared to placebo on the histology of the parotid gland (selected sites only) • To evaluate the safety of efgartigimod IV compared to placebo in participants with pSS • To evaluate the effect of efgartigimod IV compared to placebo on clinical efficacy parameters • To evaluate the effect of efgartigimod IV compared to placebo on STAR • To evaluate the PK of efgartigimod IV • To evaluate the PD of efgartigimod IV • To evaluate the immunogenicity of efgartigimod IV |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply: - 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) |
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E.4 | Principal exclusion criteria |
Participants will be excluded from the study if any of the following criteria apply: - 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 A detailed list is provided in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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) |
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E.5.2 | Secondary end point(s) |
• Change in the relative counts of lymphocytic infiltrate (stained for CD45) at week 24 • Change in B/B+T cell ratio at week 24 • Incidence and severity of TEAEs, AESIs, and SAEs by SOC and PT up to 35 weeks • Changes in vital sign measurements, ECG results, and clinical laboratory safety evaluations 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 • Change in clinESSDAI score at week 24 • Change in ESSPRI score at week 24 • Proportion of participants with STAR score of ≥5 at week 24 • Efgartigimod serum concentration-time profile • Values, changes from baseline, and percent reduction from baseline in total IgG levels in serum • Values, changes from baseline, and percent reduction from baseline in autoantibodies − Anti-Ro/ SS-A − Anti-La/ SS-B in serum • Incidence and prevalence of ADA against efgartigimod in serum |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end-of-study is defined as the date of the last participant’s last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |