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

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

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.

Study Overview

• Status: Completed
• Conditions: Eczema; Nummular Eczema; Dermatitis Eczema; Nummular Dermatitis
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80805
      • Technical University Munich - Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast; 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).	Drug: Apremilast; This study aims on investigating the efficacy of Apremilast in nummular eczema patients.
Experimental: Placebo + Apremilast; 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.	Drug: Apremilast; This study aims on investigating the efficacy of Apremilast in nummular eczema patients.; Drug: Placebo Oral Tablet; This study aims on investigating the efficacy of Apremilast in nummular eczema patients - placebo controlled

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
EASI	EASI 50 score at week 16 and 32 (Eczema Area and Severity Index)	week 16 and 32
Transepidermal Waterloss (TEWL)	Change From Baseline in Transepidermal Waterloss (TEWL) at week 16 and 32	week 16 and 32
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
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
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
DLQI	Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 and 32	week 16 and 32
Pruritus Visual Analog Scale (VAS)	Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16 and 32	week 16 and 32
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - weight	Assessed via physical examination (weight (kg))	week 16 and 32
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
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
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
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

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Kilian Eyerich, Technical University Munich

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Actual): September 15, 2021
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Eczematous; Dermatitis; Eczema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: AP-CL-ECZ-PI-006539

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No