E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Systemic Lupus Erythematosus (SLE) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Systemic Lupus Erythematosus (SLE) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025139 |
E.1.2 | Term | Lupus erythematosus systemic |
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 baricitinib 4-mg once daily (QD) or 2-mg daily QD compared to placebo on remission of SLE arthritis and/or rash in patients with SLE receiving concomitant standard therapy over 24 weeks. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of baricitinib 4-mg QD or 2-mg QD compared to placebo on overall SLE disease activity in patients with SLE receiving concomitant standard therapy over 24 weeks.
To evaluate the effect of baricitinib 4-mg QD or 2-mg QD compared to placebo on the Patient’s Global Assessment of Disease Activity (PATGA) in patients with SLE receiving concomitant standard therapy over 24 weeks.
To characterize the pharmacokinetics (PK) of baricitinib 4-mg QD or 2-mg QD in patients with SLE receiving concomitant standard therapy over 24 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Are at least 18 years of age.
[2] Have a positive ANA (HEp-2 ANA titer ≥1:80) and/or a positive anti-dsDNA (≥ 30 IU) as assessed by a central laboratory at screening.
[3] Have a SLEDAI-2K score ≥4 based on clinical symptoms (not including lab values) at randomization.
[4] Have active arthritis and/or active rash as defined by the SLEDAI-2K at randomization.
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E.4 | Principal exclusion criteria |
[1] Have active severe lupus nephritis
[2] Have active severe central nervous system (CNS) lupus
[3] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unaccepatable risk when taking investigational product or interfere with the interpretation of data.
[4] Have a current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection.
[5] Are currently receiving oral corticosteroids at doses >20-mg per day of prednisone (or equivalent) or have adjusted the dose of corticosteroids within 2 weeks of planned randomization.
[6] Have started treatment with or adjusted the dose of NSAIDs (for which the NSAID use is intended for treatment of signs and symptoms of SLE) within 2 weeks of screening or within 4 weeks of planned randomization.
[7] Have started treatment with or adjusted the dose of an antimalarial within 10 weeks of screening or within 12 weeks of planned randomization.
[8] Have started treatment with or adjusted the dose of an immunosuppressant within 10 weeks of screening or within 12 weeks of planned randomization.
[9] Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior to screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the proportion of patients who achieve remission of arthritis and/or rash as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Week 24 compared to baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The change will be evaluated from the baseline time point to the study week 24 time point |
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E.5.2 | Secondary end point(s) |
• Change in the proportion of patients achieving SLE Responder Index (SRI)-4 response at Week 24 compared to baseline. SRI-4 response is defined as:
o Reduction of ≥4 points from baseline in SLEDAI-2K score;
o No new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores; and
o No worsening (defined as an increase of ≥0.3 points [10mm] from baseline) in the Physician’s Global Assessment of Disease Activity.
• Change in the proportion of patients achieving a reduction of ≥4 points from baseline in SLEDAI-2K score at Week 24 compared to baseline.
• Change in SLEDAI-2K total score at Week 24 compared to baseline.
• Change in patient’s global assessment of disease activity at Week 24 compared to baseline.
• Plasma baricitinib concentrations will be analyzed using a population PK (PopPK) approach.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The change will be evaluated from the baseline time point to the study week 24 time point |
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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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 23 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Austria |
France |
Japan |
Korea, Republic of |
Mexico |
Poland |
Romania |
Spain |
Taiwan |
United Kingdom |
United States |
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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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End of the trial is the date of the last visit, last scheduled procedure shown in the Schedule of Activities, or date of discontinued participation for the last patient. |
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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 | 6 |
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 | 7 |