A Randomized, Assessor-Blinded Trial Comparing Lenalidomide and Methotrexate in Patients with Refractory Cutaneous Lupus Erythematosus

Trial ID: 2024-520089-70-00
Protocol: APHP240920
Sponsor: Assistance Publique Hopitaux De Paris

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Diseases & Conditions

Cutaneous lupus erythematosus

Objectives

The primary objective of this study is to demonstrate the superiority of lenalidomide 5 mg/day compared to oral methotrexate 15 to 20 mg/week in improving active cutaneous lupus erythematosus (CLE) lesions at week 16 in patients with isolated CLE or CLE associated with systemic lupus erythematosus (SLE). Secondary objectives include:

Evaluation of stringent skin improvement outcomes, specifically CLASI-A 70.
Assessment of the complete response rate at weeks 16 and 24.
Measurement of the impact on quality of life using the DLQI.
Evaluation of changes in SLE activity via the SLEDAI.
Assessment of glucocorticoid dose reduction.
Evaluation of skin damage using CLASI-D.
Comparison of adverse events rates between the two treatment groups.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female individuals between the ages of 18 and 65 years diagnosed with cutaneous lupus erythematosus, which may occur in isolation or in association with systemic lupus erythematosus. Inclusion requires a histologically-confirmed diagnosis and a Cutaneous Lupus Erythematosus Disease Area and Severity Index score of 8 or greater at randomization. Participants must present with active disease despite the use of antimalarial agents, stable doses of glucocorticoids, or topical therapies such as topical corticosteroids or tacrolimus. Women of childbearing potential are required to utilize highly effective contraception and undergo monthly pregnancy testing. The sponsor did not provide data regarding lifestyle considerations.

Plans and Procedures

This assessor-blinded, randomized clinical trial is designed to evaluate the efficacy of lenalidomide compared to methotrexate in patients with difficult-to-treat cutaneous lupus erythematosus. The study compares an oral dose of 5 mg/day of lenalidomide against an oral dose of 15 to 20 mg/week of methotrexate. The primary objective is to demonstrate superiority at week 16 based on the proportion of patients achieving at least a 50% decrease from baseline in the CLASI-A score. The research methodology includes a screening visit to confirm a histologically-confirmed diagnosis and ensure meeting specific inclusion criteria, such as a CLASI-A score ≥ 8. Following randomization, participants undergo regular follow-up visits to assess secondary endpoints, including CLASI-A 70 response, quality of life via the DLQI, and SLEDAI activity. The total duration of participant involvement extends through at least week 24, which includes an end-of-study assessment of CLASI-D damage and the rate of adverse events. Early termination may occur based on protocol-defined conditions or safety monitoring.

Treatment

The experimental treatment consists of lenalidomide administered in the pharmaceutical form of PHF00006MIG. The dosage is 5 mg, which is administered via the oral route once daily.

The comparator treatment involves methotrexate. This medication is administered through an oral route at a dose of 15 to 20 mg per week, depending on the weight of the participant.

Efficacy

The efficacy of lenalidomide in patients with cutaneous lupus erythematosus is evaluated through several parameters. The primary endpoint is the proportion of patients achieving a CLASI-A 50 response, defined as a decrease of at least 50% from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 16, for participants with a baseline score of at least 8. Secondary endpoints include the percentage of patients reaching a CLASI-A 70 response at weeks 16 and 24, and the proportion of participants achieving a complete or almost complete response (CLASI-A 0-3) at weeks 16 and 24.

Additional efficacy assessments involve:

Variation in quality of life measured by the Dermatology Life Quality Index (DLQI) at weeks 16 and 24.
Systemic lupus erythematosus (SLE) activity measured using the SLE Disease Activity Index (SLEDAI) at each visit.
Assessment of SLE flares using the SENELA-SLEDAI Flare Index (SFI) at each visit.
Variation in glucocorticoid (GC) dose between inclusion and week 24.
Variation in damage assessed via the CLASI-D score at weeks 16 and 24.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patients of at least 18 years of age
Affiliated to the French social security
Able to provide written informed consent
Histologically-confirmed diagnosis of active CLE with or without associated SLE, either historical or at screening
CLASI-A score ≥ 8 at randomization
Active CLE despite 1) AMs agents used for at least 3 months and at stable dose for at least 30 days prior to randomization or previously documented discontinuation of AMs due to poor tolerability an/or side effect and/or 2) stable dose of GCs ≤15mg/day and/or 3)stable dose of topical corticosteroids (TCS) or topical tacrolimus for at least 30 days prior to randomization
Women of childbearing potential who accept monthly plasma pregnancy test and using highly "LEISURE" protocol, version 1.0 of 25/07/2025 10/74 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited. Version 4.0 dated 31/05/2019 effective contraception for at least 4 weeks before and until 4 weeks following end of treatment; Men participant using contraceptive methods from start of treatment until 1 month after the end of treatment (according to the CRAT recommendations and SMPC)

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Exclusion Criteria

Kidney function, liver function, cell blood count and infectious serology incompatible with receiving the study treatments, according to the SMPC of each drug
Alcoholism (1/ more than 10 standard drinks per week, 2/ more than two standard drinks per day, and 3/ Less than two alcohol-free days every week))
Ongoing cancer, including solid tumors and hematologic malignancies
Active severe SLE features including lupus nephritis, neuropsychiatric SLE, serositis, severe haematological features (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) requiring high dose oral or IV GC and/or mycophenolate mofetil or cyclophosphamide
Medications: 1) Previous failure of methotrexate and lenalidomide prescribed for active CLE ; 2) Use of classical immunosuppressant drugs (mycophenolate mofetil, azathioprine), thalidomide, dapsone, retinoids, Janus Kinase inhibitors for CLE or SLE 4 weeks before screening ; 3) Use of biological therapy for CLE or SLE (including belimumab, rituximab, obinituzumab, ustekinumab, anifrolumab) 12 weeks before screening
Any contraindication to the active substances or excipients in the experimental study treatments and auxiliary treatments
Arterial or unprovoked venous thromboembolic events ≤ 5 years (for note antiphospholipid syndrome treated with vitamin K antagonist without thromboembolic events in the last 5 years or patients with positive antiphospholipid autoantibodies will NOT be excluded)
Pregnant women, breastfeeding or planning to become pregnant during the study treatment "LEISURE" protocol, version 1.0 of 25/07/2025 11/74 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited. Version 4.0 dated 31/05/2019 period and 1 month after the last dose of study treatment (according to the CRAT recommendation and SMPC)
Patients under legal protection and inability to comply with study requirement
Participation in another clinical trial on a medicinal product, clinical investigation study or RIPH1 interventional study