Clinical trial NCT03160248: An Investigator-initiated Study of Apremilast to Demonstrate Efficacy Nummular Eczema
Official title: An Investigator-initiated, Randomized, Double-blind, Placebo Controlled Study of Apremilast to Demonstrate Efficacy in Subjects With Nummular Eczema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nummular Eczema
Eczema
Dermatitis Eczema
Nummular Dermatitis
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2017-05-19
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: PGA
timeFrame: week 16
Secondary outcomes:
measure: EASI
timeFrame: week 16 and 32
measure: Transepidermal Waterloss (TEWL)
timeFrame: week 16 and 32
measure: Histology
timeFrame: week 16
measure: Use of topical steroids
timeFrame: week 16 and 32
measure: PGA score Arm 2
timeFrame: week 32
measure: DLQI
timeFrame: week 16 and 32
measure: Pruritus Visual Analog Scale (VAS)
timeFrame: week 16 and 32
measure: TSQM
timeFrame: week 16 and 32
measure: Safety: Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast
timeFrame: week 36
Other outcomes:
measure: Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - weight
timeFrame: week 16 and 32
measure: Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - BMI
timeFrame: week 16 and 32
measure: Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - abdominal girth
timeFrame: week 16 and 32
measure: Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - serum parameters
timeFrame: week 16 and 32
measure: Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - characterization of molecular (gene expression profil)
timeFrame: week 16 and 32
Locations:
city: Munich
country: Germany
facility: Technical University Munich - Department of Dermatology
state: Bavaria
Study officials:
affiliation: Technical University Munich
name: Kilian Eyerich
role: PRINCIPAL_INVESTIGATOR
References: