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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03742037
Recruitment Status : Completed
First Posted : November 15, 2018
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Study Description
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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).

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Cenerimod 0.5 mg Drug: Cenerimod 1 mg Drug: Cenerimod 2 mg Drug: Cenerimod 4 mg Drug: Placebo Phase 2

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).

813 adult subjects with SLE have been screened and 427 subjects randomized in a 1:1:1:1:1 ratio to placebo, 0.5, 1, 2, or 4 mg once daily (o.d.) of cenerimod, in addition to background SLE therapy.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 427 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants randomized to the 4 mg arm who are still on treatment at month 6 will be re-randomized in a 1:1 ratio to placebo or cenerimod 2 mg to enter treatment period 2 and will continue study treatment for a total maximum of 12 months.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : December 21, 2018
Actual Primary Completion Date : August 31, 2021
Actual Study Completion Date : August 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment Period 1: Cenerimod 0.5 mg

Participants 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).

Participants completing TP1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes the 6-month visit. This will trigger the end of treatment for all participants.

 Drug: Cenerimod 0.5 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg
Experimental: Treatment Period 1: Cenerimod 1 mg

Participants 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).

Participants completing TP1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant in TP1 completes the 6-month visit. This will trigger the end of treatment for all participants.

 Drug: Cenerimod 1 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg
Experimental: Treatment Period 1: Cenerimod 2 mg

Participants will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment period.

Participants completing TP1 will continue their study double-blind treatment unchanged during Treatment Period 2 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 participants.

 Drug: Cenerimod 2 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
Experimental: Treatment Period 1: Cenerimod 4 mg

Participants will receive cenerimod once daily in addition to background SLE therapy and will enter a 6-month double-blind study treatment period 1.

Participants completing Treatment Period 1 will be re-randomized in a double-blinded fashion in Treatment Period 2 in a 1:1 ratio to placebo or cenerimod 2 mg.

 Drug: Cenerimod 4 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg
Placebo Comparator: Treatment Period 1: Placebo

Participants 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).

Participants completing Treatment Period 1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes the 6-month visit. This will trigger the end of treatment for all participants.

 Drug: Placebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod
Experimental: Treatment Period 2: Cenerimod 2 mg (after Cenerimod 4 mg in Treatment Period 1)

Participants completing 4 mg cenerimod in Treatment Period 1 will be re-randomized in a double-blinded fashion in Treatment Period 2 in a 1:1 ratio to cenerimod 2 mg (or to placebo).

Participants completing the 4 mg cenerimod arm in Treatment Period 1 will continue with 2 mg cenerimod in Treatment Period 2 for up to 6 additional months, or until last participant completes the 6-month visit. This will trigger the end of treatment for all participants.

 Drug: Cenerimod 2 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
Placebo Comparator: Treatment Period 2: Placebo (after Cenerimod 4 mg in Treatment Period 1)

Participants completing 4 mg cenerimod in Treatment Period 1 will be re-randomized in a double-blinded fashion in Treatment Period 2 in a 1:1 ratio to placebo (or cenerimod 2 mg).

Participants completing the 4 mg cenerimod arm in Treatment Period 1 will continue with placebo in Treatment Period 2 for up to 6 additional months, or until last participant completes the 6-month visit. This will trigger the end of treatment for all participants.

 Drug: Placebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod
Experimental: Treatment Period 2: Cenerimod 0.5 mg (after Cenerimod 0.5 mg in Treatment Period 1)
Participants completing Treatment Period 1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes their 6-month visit. This will trigger the end of treatment for all participants.
 Drug: Cenerimod 0.5 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg
Experimental: Treatment Period 2: Cenerimod 1 mg (after Cenerimod 1 mg in Treatment Period 1)
Participants completing Treatment Period 1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes their 6-month visit. This will trigger the end of treatment for all participants.
 Drug: Cenerimod 1 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg
Experimental: Treatment Period 2: Cenerimod 2 mg (after Cenerimod 2 mg in Treatment Period 1)
Participants completing Treatment Period 1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes their 6-month visit. This will trigger the end of treatment for all participants.
 Drug: Cenerimod 2 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
Placebo Comparator: Treatment Period 2: Placebo (after Placebo in Treatment Period 1)
Participants completing Treatment Period 1 will continue their study double-blind treatment unchanged during Treatment Period 2 for up to 6 additional months, or until last participant completes their 6-month visit. This will trigger the end of treatment for all participants.
 Drug: Placebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Informed Consent Form 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 (anti-dsDNA) 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 6 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 (Central Nervous System) 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 (Heart Rate) 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 (White Blood Cell) 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 (sphingosine-1-phosphate) receptor modulators or any of the cenerimod formulation excipients
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03742037


Locations
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Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.
Investigators
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Study Director: ClinicalTrials Idorsia Pharmaceuticals
More Information
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Responsible Party: Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT03742037    
Other Study ID Numbers: ID-064A202
2018-001808-11 ( EudraCT Number )
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Idorsia Pharmaceuticals Ltd.:
Musculoskeletal and connective tissue disorders
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases