A research study to evaluate the effects of a new oral drug called cenerimod in adults with Systemic Lupus Erythematosus disease

• Register: EUCTR
• Last refreshed on: 5 January 2021
• Main ID: EUCTR2018-001808-11-GB
• Date of registration: 17/09/2018
• Prospective Registration: Yes
• Primary sponsor: Idorsia Pharmaceuticals Ltd
• Public title: A research study to evaluate the effects of a new oral drug called cenerimod in adults with Systemic Lupus Erythematosus disease
• Scientific title: A Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability of cenerimod in subjects with moderate to severe systemic lupus erythematosus (SLE) - CARE: Cenerimod Assessing S1P1 Receptor modulation in Systemic Lupus Erythematosus
• Date of first enrolment: 17/12/2018
• Target sample size: 325
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001808-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Chile, Czechia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Mexico, Philippines, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Disclosure Desk
• Affiliation: Idorsia Pharmaceuticals Ltd

• Name: Clinical Trial Disclosure Desk
• Affiliation: Idorsia Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Signed Informed Consent Form (ICF) prior to any study-mandated procedure.
- Diagnosis of systemic lupus erythematosus (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 modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score = 6 of at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
- 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):
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 310
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe systemic lupus erythematosus
MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Cenerimod
Product Code: ACT-334441
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cenerimod
Current Sponsor code: ACT-334441
Other descriptive name: ACT-334441
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Cenerimod
Product Code: ACT-334441
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cenerimod
Current Sponsor code: ACT-334441
Other descriptive name: ACT-334441
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Cenerimod
Product Code: ACT-334441
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cenerimod
Current Sponsor code: ACT-334441
Other descriptive name: ACT-334441
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Cenerimod
Product Code: ACT-334441
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cenerimod
Current Sponsor code: ACT-334441
Other descriptive name: ACT-334441
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change from baseline to Month 6 in the Modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score

Secondary Objective: 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

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).

Main Objective: 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

Secondary Outcome(s)

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.

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.

Secondary ID(s)

ID-064A202

NCT03742037

2018-001808-11-FR

Source(s) of Monetary Support

Idorsia Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date: 17/12/2018
Contact: