?dult subjects of any ethnicity and either gender with Subacute Cutaneous Lupus Erythematosus (SCLE), Discoid Lupus Erythematosus (DLE), Lupus erythematosus tumidus (LET) or Systemic Lupus Erythematosus (SLE) with DLE or SCLE lesions and without major organ involvement to investigate the efficacy of alitretinoin (30 mg per day) in the treatment of Cutaneous Lupus Erythematosus lesions. MedDRA version: 16.0 Level: PT Classification code 10056509 Term: Cutaneous lupus erythematosus System Organ C
Conditions
Interventions
Trade Name: Toctino®
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ALITRETINOIN
CAS Number: 5300-03-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Sponsors
Universitätsklinikum Münster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients of any gender aged from 18 to 75 years; 2. A clinical and histological diagnosis of CLE (DLE, SCLE, LET without major systemic involvement) who failed to response to topical corticosteroids; 3. Total RCLASI activity score of >6 (at least 3 points in at least 2 locations) on an assessment of erythema, scale/ hyperkeratosis, edema/infiltration and subcutaneous nodule/plaque of the lesion (mucous membrane lesions/ alopecia excluded); 4. Women of childbearing potential must agree to use at least one primary method of contraception but preferably 2 methods of contraception under supervision of the investigator or a gynecologist 5. Signed informed consent. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Patients unable to comply with the requirements of the study; 2. Only scarred cutaneous target lesions without activity; 3. Systemic Lupus Erythematosus (SLE) with major systemic organ involvement, e.g. clinical significant renal involvement, requiring systemic medical treatment for the disease; 4. Active skin disease other than CLE or another progressive or serious disease that interferes with the study outcome; 5. Symptoms of a clinically significant illness that may influence the outcome of the study in the four weeks before and during the study; 6. Active severe infection diseases, including chronic or localized; 7. Patients with hepatic insufficiency, severe renal failure, or uncontrolled hypercholesterinemia, uncontrolled as characterized by: i. Fasting triglyceridemia > 1.5 x upper limit of normal (ULN) ii. Fasting cholesterol > 1.5 x ULN iii. Fasting low-density lipoprotein (LDL) cholesterol > 1.5x ULN 8. Patients with known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil; 9. Patients with hypothyroidism or hypervitaminosis A; 10. Patients with cardiovascular risk factors that would exclude a starting dose of 30 mg of alitretinoin; 11. Topical corticosteroids within 14 days prior to dosing; 12. Patients treated with any systemic or topical retinoids within 4 weeks before start of study treatment; 13. Patients receiving drugs with a potential for drug-drug interaction, such as systemic tetracyclines, ketoconazole, or St. John’s Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment; 14. Initiation or change in the dose of any current systemic medication for the treatment of CLE/SLE prior to the study (time depending on drug class and half-life); 15. Treatment with immunosuppressive drugs for other reasons, 4 weeks prior and within the study; 16. Concomitant treatment with drugs with a known photosensitizing potential, e.g. tetracyclines, griseofulvin, thiazides, furosemide, sulfonamides or tolebutamide; 17. Drugs associated to CLE-induction: terbinafine, hydrochlorothiazide, diltiazem, verapamil, nifedipine, nitrendipine, fluorouracil, penicillamine, infliximab, adalimumab, etanercept, pantoprazole; 18. Participation in another clinical trial including the four week period preceding the study or having received a non-licensed drug within the last 3 months prior to the study; 19. Pregnancy (according to pregnancy test) or nursing. 20. Patients with hereditary myopathy in patient and family history; 21. Patients with known rhabdomyolysis in patient history (e.g. musculous-toxic complications in association with statin and fibrate therapy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the therapeutic effect of alitretinoin (Toctino®) in the treatment of Cutaneous Lupus Erythematosus with respect to proportion of responders based on the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI) activity score for skin lesions at baseline and after 24 weeks of treatment or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF). Response is defined as a reduction of 50% in the total RCLASI compared to the baseline value ("RCLASI 50");Secondary Objective: • To evaluate the proportion of responders after 12 weeks of treatment • To evaluate the treatment effect of alitretinoin (Toctino®) with respect to change from baseline in the total RCLASI activity score for skin lesions in comparison to week 12, and to the last day of treatment. • Time from start of treatment to first response (time to response). • To evaluate the proportion of failures of treatment after 12 and 24 weeks of treatment. • To evaluate the Patient Assessment of Global Improvement (PAGI) score as well as subject’s assessment of itching and pain assessed by a visual analogue scale (VAS) at baseline, as well as after 12 and 24 weeks of treatment. • To evaluate the safety and tolerability aspects of alitretinoin (Toctino®) in patients with CLE for the body as a whole.;Primary end point(s): Primary efficacy outcome is the response rate at week 24 or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF). Response is defined as a reduction of 50% in the total RCLASI activity for skin lesions, compared to the baseline value ("RCLASI 50");Timepoint(s) of evaluation of this end point: The endpint will be evaluated after the last subject has completed the Study Completion Visit, any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator, and the database is closed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): n.a.;Timepoint(s) of evaluation of this end point: n.a. | — |
Countries
Germany
Contacts
Public ContactAnnegret Kuhn
Universitätsklinikum Münster
Outcome results
None listed