Lenalidomide versus methotrexate in difficult-to-treat cutaneous lupus erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC National - Ministère des solidarités et de la Santé

External identifiers

EU CT number

2024-520089-70-00

ClinicalTrials.gov

NCT06965244

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the superiority of lenalidomide 5 mg/day versus oral methotrexate 15 to 20 mg/week (according to patient weight) at week 16 for improving active CLE lesions for patients with isolated CLE or CLE associated with SLE

Secondary objectives 7

1. To evaluate more stringent outcomes of skin improvement such as CLASI-A 70
2. To evaluate the rate of complete response at week 16 and week 24
3. To evaluate the impact of both treatments on QoL
4. To evaluate the impact of both treatment on SLE activity
5. To evaluate the impact of both treatment on GCs dose reduction
6. To evaluate the impact of both treatment on CLE damage assessed by CLASI-D
7. To compare the rate of AEs between the two groups

Conditions and MedDRA coding

Cutaneous lupus erythematosus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients of at least 18 years of age
2. Affiliated to the French social security
3. Able to provide written informed consent
4. Histologically-confirmed diagnosis of active CLE with or without associated SLE, either historical or at screening
5. CLASI-A score ≥ 8 at randomization
6. 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
7. 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)

Exclusion criteria 10

1. Kidney function, liver function, cell blood count and infectious serology incompatible with receiving the study treatments, according to the SMPC of each drug
2. 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))
3. Ongoing cancer, including solid tumors and hematologic malignancies
4. 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
5. 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
6. Any contraindication to the active substances or excipients in the experimental study treatments and auxiliary treatments
7. 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)
8. 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)
9. Patients under legal protection and inability to comply with study requirement
10. Participation in another clinical trial on a medicinal product, clinical investigation study or RIPH1 interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the proportion of patients who achieve decrease of at least 50% from baseline in the CLASI activity (CLASI-A) score (CLASI-A 50 response) at week 16 with at least 8 of CLASI-A at baseline.

Secondary endpoints 12

1. Percentage of patients reaching CLASI-A 70, a 70% decrease from baseline CLASI-A at week 16
2. Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3) at week 16
3. Percentage of patients reaching CLASI-A 70, a 70% decrease from baseline CLASI-A at week 24
4. Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3) at week 24
5. Variation of Quality of life using DLQI at week 16
6. Variation of Quality of life using DLQI at week 24
7. SLE activity using SLEDAI at each visit
8. SLE flare using SENELA-SLEDAI Flare Index (SFI) at each visit
9. Variation of GCs dose between inclusion and week 24.
10. Variation of damage in each group using CLASI-D at week 24
11. Variation of damage in each group using CLASI-D at week 16
12. Rate of adverse events during the treatment and the follow-up periods

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr François CHASSET

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr François CHASSET

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications