| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe systemic lupus erythematosus |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10042945 |
| E.1.2 | Term | Systemic lupus erythematosus |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| 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 assess the efficacy of 6 months cenerimod treatment given at 4 different dose levels (0.5, 1, 2, and 4 mg once daily) on disease activity in adult subjects with moderate to severe SLE concurrently receiving background therapy |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate over 6 months in adult subjects with moderate to severe SLE concurrently receiving background therapy:
• the safety and tolerability of cenerimod treatment
• the effect of cenerimod treatment on quality of life and fatigue using relevant patient reported outcome (PRO) instruments
• the effect of cenerimod treatment on SLE biomarkers
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
At randomization, approximately 175 subjects will be assigned to the
echocardiography ancillary study through the IRT system. The
echocardiography ancillary study will run concurrently with the main
study. Subjects assigned into the echocardiography ancillary study will
undergo an echocardiography assessment at Month 6, or at premature
End-of-Treatment (pEOT) visit in case of premature study treatment
discontinuation during treatment period 1, in addition to
echocardiography assessments that will be performed for all subjects
during the screening period. |
|
| E.3 | Principal inclusion criteria |
- Signed ICF prior to any study-mandated procedure
- Diagnosis of SLE made at least 6 months prior to Screening, by fulfilling at least 4 of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR) criteria
- A mSLEDAI-2K score ≥ 6 of at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). The mSLEDAI-2K score does not take into account “leukopenia”
- Currently treated with stable doses of one or more of the following background medications:
• NSAIDs
• Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine)
• Mycophenolate mofetil (≤ 2 g/day)
• Mycophenolic acid (≤ 1440 mg/day)
• Azathioprine (≤ 2 mg/kg/day)
• Methotrexate (≤ 20 mg/week)
• Corticosteroids (≤ 40 mg/day prednisone or equivalent)
• Belimumab (≤ 10 mg/kg every 4 weeks intravenously [i.v.], or 200
mg/week subcutaneously [s.c.]).
- Presence of at least one of the following autoantibodies measured by
central laboratory defined as follows: (a) Positive antinuclear antibody
(ANA) test measured by immunofluorescence assay (IFA) with titre ≥
1:80; or (b) positive anti-double stranded deoxyribonucleic acid (antidsDNA)
antibodies with titre ≥30 IU/mL.
- Women of childbearing potential (WOCBP):
- History or presence of positive autoantibodies measured by central laboratory defined as follows: (a) Positive antinuclear antibody (ANA) test measured by immunofluorescence assay (IFA) with titre ≥1:80; AND/OR (b) positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies with titre ≥30 IU/mL
- Women of childbearing potential (WOCBP):
• Must have a negative serum pregnancy test at Screening
• Must agree to undertake monthly urine pregnancy tests during the study
• Must use highly effective methods of contraception from the screening visit until 4 months after taking the last dose of study treatment
|
|
| E.4 | Principal exclusion criteria |
- Active lupus nephritis or a renal biopsy demonstrating immune
complex-mediated glomerulonephritis compatible with lupus nephritis
within 90 days prior to Screening.
- Severe active central nervous system (CNS) lupus requiring therapeutic
intervention (including aseptic meningitis, seizures, psychosis,
cerebritis, cerebrovascular accident [CVA], organic brain syndrome, CNS
vasculitis) and severe forms of vasculitis requiring systemic
immunosuppressive treatment (including retinal vasculitis, coronary
vasculitis, pulmonary vasculitis, mesenteric vasculitis) within 90 days
prior to Screening.
- A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with rheumatoid arthritis, erosive arthritis, scleroderma or autoimmune hepatitis.
- History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders.
- Subjects who experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, vascular thrombosis, decompensated heart failure requiring hospitalization, or heart failure defined by the New York Heart Association Class III/IV within six months prior to Screening.
- An elevated QT corrected for HR on the basis of Fridericia’s formula interval of > 470 ms (females) / > 450 ms (males).
- History of clinically relevant bronchial asthma or chronic obstructive
pulmonary disease that has required treatment with oral or parenteral
corticosteroids for more than 2 weeks within the last 6 months prior to
Screening.
- History or presence of severe respiratory disease or pulmonary fibrosis.
- Active or latent tuberculosis .
- Ongoing bacterial, viral or fungal infection that is of clinical concern in the judgment of the investigator or history of any serious infection.
- Subjects who have congenital or acquired severe immunodeficiency or known HIV infection or positive HIV testing.
- Presence of macular edema or active uveitis.
- Type 1 or 2 diabetes that is poorly controlled according to investigator judgment, or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy.
- Significant hematology abnormality: Lymphocyte count < 800 /μL (0.8 × 10e9/L); hemoglobin < 9 g/dL; WBC count < 2500/μL (2.5 × 10e9/L) or platelets < 75000/μL (75 × 10e9/L).
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2.
- Known allergy to S1P receptor modulators or any of the cenerimod formulation excipients
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to Month 6 in the mSLEDAI-2K score |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline (Baseline is defined as the last available measurement
before the start of randomized) to Month 6 (Day 180). |
|
| E.5.2 | Secondary end point(s) |
1. Response on Systemic Lupus Erythematosus Responder Index (SRI-4)
at Month 6 as compared to baseline, defined as follows:
- Reduction from baseline of at least 4 points in the mSLEDAI-2K
AND
- No new British Isles Lupus Assessment Group (BILAG) A organ domain
score and no more than one new BILAG B organ domain score compared
with baseline
AND
- No increase of more than 0.3 points on the Physician's Global
Assessment (PGA) since baseline.
2. Response (no worsening) at Month 6 on BILAG-2004 disease activity
index defined as no new BILAG A organ domain score and no more than
one new BILAG B organ domain score compared with baseline. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Response on Systemic Lupus Erythematosus Responder Index (SRI-4)
at Month 6 (Day 180) after start of treatment.
2. Response on BILAG-2004 disease activity index at Month 6 (Day 180)
after start of treatment. |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Biomarkers, tolerability, patient reported outcomes, quality of life |
|
| 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 | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 67 |
| 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 |
| Chile |
| Georgia |
| Israel |
| Mexico |
| Philippines |
| Russian Federation |
| Taiwan |
| Thailand |
| Turkey |
| Ukraine |
| United States |
| Bulgaria |
| Czechia |
| France |
| Greece |
| Italy |
| Poland |
| Romania |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 40 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 42 |
Print
