An Investigator-initiated Study of Apremilast to Demonstrate Efficacy Nummular Eczema (APREMINUM)

Technical University of Munich

Status and phase: Completed; Phase 2

Conditions: Dermatitis Eczema; Nummular Eczema; Nummular Dermatitis; Eczema

Treatments: Drug: Apremilast; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03160248

AP-CL-ECZ-PI-006539

Details and patient eligibility

About

This is an investigator-initiated, single-center, prospective, randomized, double-blind, interventional phase IIb study. Forty patients with clinically and histologically confirmed nummular eczema will be enrolled according to inclusion and exclusion criteria. Patients will be included after written informed consent is obtained. Prior to randomization, average application rate of class II topical steroids per day will be measured for 4 weeks. Subsequently, patients will be randomized in a 1:1 ratio into one arm to receive Apremilast 30 mg BID (following titration phase) for 16 weeks or a second arm receiving identically matching placebo for 16 weeks. From beginning of week 17, all patients will start an open-label treatment with Apremilast 30 mg BID until week 32. Concomitant use of topical steroids (class II) is allowed during the study. During the treatment period both placebo and Apremilast will be applied p.o. from week 0 until week 32.

Enrollment: 31 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Clinically confirmed diagnosis of nummular eczema
2. Biopsy-proven, meaning histology consistent with eczema (including PAS-staining)
3. PGA ≥ 3 on a 5 point scale
4. History of continuous use of topical steroids for the last 8 weeks
5. Age 18-85 years of age, body weight ≥ 40 kg and ≤ 160 kg
6. Signed informed consent from patient

Exclusion criteria

1. Permanent severe diseases, especially those affecting the immune system

2. Pregnancy or breast feeding

3. History or presence of epilepsy, significant neurological disorders, depression, suicidal ideation and behaviour, cerebrovascular attacks or ischemia

4. History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy

5. Evidence of severe renal dysfunction defined as:

   • eGFR < 30 ml/min/1,73 m2 (calculated using the MDRD formula) at screening (Visit 1)

6. Evidence of significant hepatic disease defined as:

   At screening (Visit 1):

   • Alkaline phosphatase >3x upper limit of normal (ULN) or alkaline phosphatase >2,5x ULN and total bilirubin > 2xULN or
   • Aspartate transaminase (AST, SGOT]) and alanine transaminase (ALT, SGPT]) > 2.5x upper limit of normal (ULN)

7. History of lymphoproliferative disorders

8. Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits

9. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they use effective contraception during the study and for 4 weeks after study completion or discontinuation. The chosen form of birth control must be effective by the time the patient receives her first dose of study drug.

10. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)

11. Inability or unwillingness to undergo repeated punch biopsies

12. History of allergy to any component of the study medication

13. Current use of strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin and St John's wort)

14. Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption

15. Evidence of acute contact dermatitis at screening

16. Evidence of underweight, defined as BMI < 18,5 kg/m2

17. Evidence of Zink deficiency defined as Zink level < 20 µg/dL in serum

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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31 participants in 2 patient groups

Apremilast

Experimental group

Description:

Patients randomized to this arm will start Apremilast with a titration phase of 5 days, followed by 30 mg Apremilast tablets twice daily (BID) by mouth (PO) for a total of 32 weeks (including titration phase).

Treatment:

Drug: Apremilast

Placebo + Apremilast

Experimental group

Description:

Patients randomized to this arm will receive identically matching placebo (including the titration phase) by mouth for first 16 weeks. Placebo participants will be switched to receive Apremilast 30 mg BID from beginning of Week 17 for another 16 weeks. In this arm Apremilast will be started without titration.

Treatment:

Drug: Placebo Oral Tablet

Drug: Apremilast