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

Eczema Clinical Trial

— APREMINUM  

Official title:

An Investigator-initiated, Randomized, Double-blind, Placebo Controlled Study of Apremilast to Demonstrate Efficacy in Subjects With Nummular Eczema

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160248
• Other study ID #: AP-CL-ECZ-PI-006539
• Status: Completed
• Phase: Phase 2
• Start date: July 5, 2017
• Est. completion date: September 15, 2021

Study information

• Verified date: October 2020
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 15, 2021
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis Eczema
• Eczema
• Nummular Dermatitis
• Nummular Eczema

Intervention

Drug:
• Apremilast
This study aims on investigating the efficacy of Apremilast in nummular eczema patients.
• Placebo Oral Tablet
This study aims on investigating the efficacy of Apremilast in nummular eczema patients - placebo controlled

Locations

Country	Name	City	State
Germany	Technical University Munich - Department of Dermatology	Munich	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
Technische Universität München	Celgene Corporation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - weight	Assessed via physical examination (weight (kg))	week 16 and 32
Other	Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - BMI	Assessed via physical examination (BMI (kg/m2))	week 16 and 32
Other	Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - abdominal girth	Assessed via physical examination (abdominal girth (cm)))	week 16 and 32
Other	Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - serum parameters	Assessed via serum parameters (glucose, HbA1c, cholesterol, HDL, LDL, Lipoprotein (a))	week 16 and 32
Other	Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - characterization of molecular (gene expression profil)	Changes in metabolic functions during treatment with Apremilast vs. Placebo in the skin (biopsies at week 0 and week 16) as determined by RNA sequencing (RNAseq).	week 16 and 32
Primary	PGA	Number of Patients Achieving an Improvement (Decrease) in PGA (Physician Global Assessment) by two or more points at week 16 as compared to week 0 or achieving an absolute PGA of 0 or 1 at Week 16	week 16
Secondary	EASI	EASI 50 score at week 16 and 32 (Eczema Area and Severity Index)	week 16 and 32
Secondary	Transepidermal Waterloss (TEWL)	Change From Baseline in Transepidermal Waterloss (TEWL) at week 16 and 32	week 16 and 32
Secondary	Histology	Significant histological improvement at week 16 - Assessed by reduction of epidermal thickness > 30% or reduction of inflammatory infiltrate > 50 % compared to histological findings on baseline.	week 16
Secondary	Use of topical steroids	Change From Baseline in the Reduction of the Use of Topical Steroids at week 16 and 32; - Prior to randomization and during the treatment, average application rate of class II topical steroids per day will be calculated. Participants will receive "prednicarbate" from the study centre. On each visit the tube will be weighed to measure usage.	week 16 and 32
Secondary	PGA score Arm 2	Change in PGA score compared to baseline and week 16 for patients in Arm 2 at week 32; - Comparison of the first and the second 16 weeks of the trial in terms of the change in PGA score from baseline for patients in Arm 2	week 32
Secondary	DLQI	Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 and 32	week 16 and 32
Secondary	Pruritus Visual Analog Scale (VAS)	Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16 and 32	week 16 and 32
Secondary	TSQM	Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 16 and 32	week 16 and 32
Secondary	Safety: Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast	Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast	week 36