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Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT03742037
Recruitment Status : Active, not recruiting
First Posted : November 15, 2018
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Tracking Information
First Submitted Date  ICMJE November 12, 2018
First Posted Date  ICMJE November 15, 2018
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE December 21, 2018
Estimated Primary Completion Date May 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
Change from baseline to month 6 in the modified SLEDAI (mSLEDAI) score [ Time Frame: From baseline up to month 6 ]
This endpoint is based on the SLEDAI-2K index, modified to exclude leukopenia. All values of mSLEDAI-2K from baseline through Month 6 visits will be accounted for in the assessment of this endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at month 6 as compared to baseline [ Time Frame: At month 6 after study treatment initiation ]
  • Percent of subjects with no new organ system affected as defined by one or more BILAG A or 2 or more BILAG B items as compared with baseline [ Time Frame: At month 6 after study treatment initiation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Official Title  ICMJE 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)
Brief Summary The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with systemic lupus erythematosus (SLE).
Detailed Description

This is a Phase 2b, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).

Approximately 500 adult subjects with SLE will be randomized in a 1:1:1:1:1 ratio to placebo, 0.5, 1, 2, or 4 mg o.d. of cenerimod, in addition to background SLE therapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: Cenerimod 0.5 mg
    Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg
  • Drug: Cenerimod 1 mg
    Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg
  • Drug: Cenerimod 2 mg
    Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
  • Drug: Cenerimod 4 mg
    Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg
  • Drug: Placebo
    Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod
Study Arms  ICMJE
  • Experimental: Cenerimod 0.5 mg

    Subjects will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment called Treatment Period 1 (TP1).

    Subjects completing TP1 will continue their study double-blind treatment unchanged during TP2 for up to 6 additional months, or until last subject in TP1 completes the 6-month visit. This will trigger the end of treatment for all subjects.

    Intervention: Drug: Cenerimod 0.5 mg
  • Experimental: Cenerimod 1 mg

    Subjects will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment called Treatment Period 1 (TP1).

    Subjects completing TP1 will continue their study double-blind treatment unchanged during TP2 for up to 6 additional months, or until last subject in TP1 completes the 6-month visit. This will trigger the end of treatment for all subjects.

    Intervention: Drug: Cenerimod 1 mg
  • Experimental: Cenerimod 2 mg

    Subjects will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment called Treatment Period 1 (TP1).

    Subjects completing TP1 will continue their study double-blind treatment unchanged during TP2 for up to 6 additional months, or until last subject in TP1 completes the 6-month visit. This will trigger the end of treatment for all subjects.

    Intervention: Drug: Cenerimod 2 mg
  • Experimental: Cenerimod 4 mg

    Subjects will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment called Treatment Period 1 (TP1).

    Subjects completing TP1 will will be re-randomized in a double-blinded fashion in TP2 in a 1:1 ratio to placebo or cenerimod 2 mg.

    Intervention: Drug: Cenerimod 4 mg
  • Placebo Comparator: Placebo

    Subjects will receive matching placebo once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment called Treatment Period 1 (TP1).

    Subjects completing TP1 will continue their study double-blind treatment unchanged during TP2 for up to 6 additional months, or until last subject in TP1 completes the 6-month visit. This will trigger the end of treatment for all subjects.

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2018)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 15, 2021
Estimated Primary Completion Date May 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
  • 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, or 200 mg/week subcutaneously)
  • 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 (antidsDNA) antibodies with titre ≥30 IU/mL
  • Women of childbearing potential:

    • 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

Exclusion Criteria:

  • Active lupus nephritis or a renal biopsy demonstrating immune complex mediated glomerulonephritis compatible with lupus nephritis.
  • CNS lupus and severe forms of vasculitis requiring systemic immunosuppressive treatment
  • 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Chile,   Czechia,   France,   Georgia,   Greece,   Hungary,   Israel,   Italy,   Mexico,   Philippines,   Poland,   Romania,   Russian Federation,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Germany,   Lithuania
 
Administrative Information
NCT Number  ICMJE NCT03742037
Other Study ID Numbers  ICMJE ID-064A202
2018-001808-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Idorsia Pharmaceuticals Ltd.
Study Sponsor  ICMJE Idorsia Pharmaceuticals Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ClinicalTrials Idorsia Pharmaceuticals
PRS Account Idorsia Pharmaceuticals Ltd.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP