A Multicenter,Open-label,Single Arm,Multiple-dose Study to Evaluate the Safety,Tolerability,Pharmacokinetics and Pharmacodynamics of Cenerimod in Adult Chinese Participants With Moderate-to-severe Systemic Lupus Erythematosus (SLE) on Top of Background Therapy
Overview
- Phase
- Phase 2
- Intervention
- cenerimod 4 mg
- Conditions
- Not specified
- Sponsor
- Viatris Pharmaceuticals Co., Ltd.
- Enrollment
- 15
- Locations
- 8
- Primary Endpoint
- Change from baseline in 12-lead electrocardiogram (ECG) parameters
- Status
- Enrolling by Invitation
- Last Updated
- 15 days ago
Overview
Brief Summary
The goal of this clinical trial is to learn about the safety, how the body processes the drug, and its effects of a drug called cenerimod in adult Chinese participants (aged 18-75) with moderate to severe Systemic Lupus Erythematosus (SLE) who are already receiving standard background therapy.
The main questions it aims to answer are:
- What is the safety and tolerability of a daily 4 mg dose of cenerimod in Chinese participants with SLE?
- How is cenerimod processed by the body (pharmacokinetics) in this population?
- What is the effect of cenerimod on the level of lymphocytes in the blood (pharmacodynamics)? This is a single-arm study without a comparison group.
Participants will:
- Take one 4 mg cenerimod tablet by mouth once daily for up to 12 months.
- Continue their stable, pre-existing background SLE medications throughout the study.
- Attend regular clinic visits over a period of up to 22 months for tests and check-ups, including blood draws, heart monitoring (12-lead electrocardiogram), vital signs(blood pressure),and physical examinations.
- Undergo a final safety follow-up 6 months after their last dose of the study drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated ICF prior to any study-mandated procedure.
- •Male and female Chinese participants aged from 18 to 75 years old (inclusive) at the time of signing the ICF.
- •Diagnosis of SLE made at least 6 months prior to Screening, according to 2019 European League Against Rheumatism / American College of Rheumatology Criteria.
- •An mSLEDAI-2K score ≥ 6 and clinical mSLEDAI-2K score ≥ 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
- •Note: The mSLEDAI-2K score does not include "leukopenia". The clinical mSLEDAI-2K is the mSLEDAI-2K assessment score without the inclusion of points attributable to hematuria, proteinuria, pyuria, urinary casts, low complement, increased DNA binding, and thrombocytopenia.
- •PGA score ≥ 1.0 on a 0 to 3 VAS.
- •Currently treated with one or more of the following SLE background medications:
- •Antimalarials: (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine),
- •Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤ 1.44 g/day),
- •Azathioprine (≤ 2 mg/kg/day),
Exclusion Criteria
- •Pregnant, planning to be become pregnant up to 6 months after the last dose of cenerimod in this study, or lactating women.
- •Active severe SLE-driven renal disease (within 90 days prior to Screening or during Screening) where, in the judgment of the investigator, protocol-specified SLE background therapy is insufficient and the use of a more aggressive therapeutic approach or other treatments not permitted in the protocol is indicated.
- •Urine protein/creatinine ratio\> 3000 mg/g (i.e., \> 339.45 mg/mmol) at Screening assessment based on central assessment.
- •Severe active central nervous system lupus or active severe or unstable neuropsychiatric SLE including but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; or mononeuritis multiplex:
- •That would make the participant unable to fully understand the ICF. or
- •Where, in the opinion of the investigator/delegate, protocol-specified standard of care is insufficient and the use of a more aggressive therapeutic approach, such as adding i.v. cyclophosphamide and/or high dose i.v. pulse corticosteroid (CS) therapy or other treatments not permitted in the protocol is indicated.
- •Severe forms of vasculitis (e.g., retinal vasculitis, coronary vasculitis, pulmonary vasculitis, mesenteric vasculitis) requiring systemic immunosuppressive treatment within 90 days prior to Screening or during Screening.
- •A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with psoriasis, rheumatoid arthritis, erosive arthritis, scleroderma, autoimmune hepatitis, or uncontrolled autoimmune thyroid disease.
- •History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia, or syncope associated with cardiac disorders.
- •Participants 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 (see Appendix 14) within 6 months prior to Screening.
Arms & Interventions
cenerimod
cenerimod 4 mg once daily
Intervention: cenerimod 4 mg
Outcomes
Primary Outcomes
Change from baseline in 12-lead electrocardiogram (ECG) parameters
Time Frame: Baseline, Month 1, Month 2, Month 3, Month 4,Month 5,Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12
Change in heart rate (HR), PR interval, QRS interval, QTcB interval, and QTcF interval from baseline to each post-baseline assessment.ECG abnormalities are assessed based on pre-defined criteria.
Number of participants with treatment-emergent adverse events (AEs)
Time Frame: From first dose of study treatment up to 180 days after the last dose
Treatment-emergent AEs are defined as any adverse event that occurs after the first dose of study treatment and up to 180 days after the last dose. This includes serious AEs (SAEs), AEs of special interest (AESIs), and AEs leading to permanent discontinuation of study treatment. AEs are coded using MedDRA and assessed by the investigator.
Change from baseline in laboratory parameters
Time Frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12
Change in hematology, blood chemistry, and urinalysis variables from baseline to each post-baseline assessment. Marked laboratory abnormalities are defined based on central laboratory reference ranges.
Number of participants with treatment-emergent medically relevant ECG abnormalities
Time Frame: Baseline to Month 12
Treatment-emergent medically relevant ECG abnormalities are defined as new or worsening abnormalities from baseline to each post-baseline assessment, as determined by central reading.
Occurrence of adverse events leading to permanent discontinuation of study treatment
Time Frame: From first dose of study treatment up to end of treatment,maximum duration of 12 months.
Number of participants who permanently discontinue study treatment due to adverse events.
Change from baseline in vital signs (systolic and diastolic blood pressure) and body weight
Time Frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12
Change in systolic blood pressure (SBP), diastolic blood pressure (DBP), and body weight from baseline to each post-baseline assessment. Measurements are performed in duplicate under standardized conditions.
Cenerimod Plasma Concentration
Time Frame: Pre-dose (0h), and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose on Day 1; Pre-dose on Day 30 (Month 1); Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose on Day 60 (Month 2); Pre-dose on Day 120 (Month 4); Pre-dose on Day 180
Plasma concentrations of cenerimod are measured at multiple time points to characterize the pharmacokinetic profile. Concentrations are determined using a validated bioanalytical method (e.g., LC-MS/MS).
Accumulation index (AI) of cenerimod
Time Frame: Between Day 1 and Month 2
AI is calculated as the ratio of AUC at steady state (Month 2) to AUC after the first dose (Day 1).
Change from baseline in total blood lymphocyte count
Time Frame: Baseline to Month 12
Change in total blood lymphocyte count from baseline to each post-baseline assessment. This is a key pharmacodynamic marker for cenerimod.
Time to maximum plasma concentration (tmax) of cenerimod
Time Frame: Day 1 and Month 2
tmax is derived from plasma concentration-time profiles using non-compartmental analysis. Assessed during the first dosing interval on Day 1 and at steady state (Month 2). Time Frame: Day 1 and Month 2
Maximum plasma concentration (Cmax) of cenerimod
Time Frame: Day 1 and Month 2
Cmax is derived from plasma concentration-time profiles using non-compartmental analysis. Assessed during the first dosing interval on Day 1 and at steady state (Month 2).
Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24) of cenerimod
Time Frame: Day 1
AUC0-24 is derived during the first dosing interval on Day 1 using non-compartmental analysis.
Area under the plasma concentration-time curve over a dosing interval at steady state (AUCτ) of cenerimod
Time Frame: Month 2
AUCτ is derived at steady state (Month 2) using non-compartmental analysis.
Number of participants with treatment-emergent marked laboratory abnormalities
Time Frame: Baseline to Month 12
Treatment-emergent marked laboratory abnormalities are defined as new or worsening abnormalities in hematology, blood chemistry, or urinalysis from baseline to each post-baseline assessment, based on central laboratory criteria.