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

Primary Purpose

Nummular Eczema, Eczema, Dermatitis Eczema

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Apremilast

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Nummular Eczema

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Permanent severe diseases, especially those affecting the immune system
Pregnancy or breast feeding
History or presence of epilepsy, significant neurological disorders, depression, suicidal ideation and behaviour, cerebrovascular attacks or ischemia
History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy
Evidence of severe renal dysfunction defined as:
- eGFR < 30 ml/min/1,73 m2 (calculated using the MDRD formula) at screening (Visit 1)
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)
History of lymphoproliferative disorders
Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits
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.
Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)
Inability or unwillingness to undergo repeated punch biopsies
History of allergy to any component of the study medication
Current use of strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin and St John's wort)
Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption
Evidence of acute contact dermatitis at screening
Evidence of underweight, defined as BMI < 18,5 kg/m2
Evidence of Zink deficiency defined as Zink level < 20 µg/dL in serum

Sites / Locations

Technical University Munich - Department of Dermatology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Apremilast

Placebo + Apremilast

Arm 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).

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

EASI

EASI 50 score at week 16 and 32 (Eczema Area and Severity Index)

Transepidermal Waterloss (TEWL)

Change From Baseline in Transepidermal Waterloss (TEWL) at 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.

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.

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

DLQI

Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 and 32

Pruritus Visual Analog Scale (VAS)

Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at 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

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

Full Information

NCT ID

NCT03160248

First Posted

May 17, 2017

Last Updated

October 7, 2021

Sponsor

Technical University of Munich

Collaborators

Celgene Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03160248

Brief Title

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

Acronym

APREMINUM

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

July 5, 2017 (Actual)

Primary Completion Date

September 15, 2021 (Actual)

Study Completion Date

September 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Technical University of Munich

Collaborators

Celgene Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nummular Eczema, Eczema, Dermatitis Eczema, Nummular Dermatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Apremilast

Arm Type

Experimental

Arm Description

Arm Title

Placebo + Apremilast

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Apremilast

Intervention Description

This study aims on investigating the efficacy of Apremilast in nummular eczema patients.

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

This study aims on investigating the efficacy of Apremilast in nummular eczema patients - placebo controlled

Primary Outcome Measure Information:

Title

PGA

Description

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

Time Frame

week 16

Secondary Outcome Measure Information:

Title

EASI

Description

EASI 50 score at week 16 and 32 (Eczema Area and Severity Index)

Time Frame

week 16 and 32

Title

Transepidermal Waterloss (TEWL)

Description

Change From Baseline in Transepidermal Waterloss (TEWL) at week 16 and 32

Time Frame

week 16 and 32

Title

Histology

Description

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.

Time Frame

week 16

Title

Use of topical steroids

Description

Time Frame

week 16 and 32

Title

PGA score Arm 2

Description

Time Frame

week 32

Title

DLQI

Description

Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 and 32

Time Frame

week 16 and 32

Title

Pruritus Visual Analog Scale (VAS)

Description

Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16 and 32

Time Frame

week 16 and 32

Title

TSQM

Description

Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 16 and 32

Time Frame

week 16 and 32

Title

Safety: Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast

Description

Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast

Time Frame

week 36

Other Pre-specified Outcome Measures:

Title

Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - weight

Description

Assessed via physical examination (weight (kg))

Time Frame

week 16 and 32

Title

Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - BMI

Description

Assessed via physical examination (BMI (kg/m2))

Time Frame

week 16 and 32

Title

Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - abdominal girth

Description

Assessed via physical examination (abdominal girth (cm)))

Time Frame

week 16 and 32

Title

Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - serum parameters

Description

Assessed via serum parameters (glucose, HbA1c, cholesterol, HDL, LDL, Lipoprotein (a))

Time Frame

week 16 and 32

Title

Exploratory endpoint: Change From Baseline in metabolic functions at Week 16 and 32 - characterization of molecular (gene expression profil)

Description

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).

Time Frame

week 16 and 32

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Clinically confirmed diagnosis of nummular eczema Biopsy-proven, meaning histology consistent with eczema (including PAS-staining) PGA ≥ 3 on a 5 point scale History of continuous use of topical steroids for the last 8 weeks Age 18-85 years of age, body weight ≥ 40 kg and ≤ 160 kg Signed informed consent from patient Exclusion Criteria: Permanent severe diseases, especially those affecting the immune system Pregnancy or breast feeding History or presence of epilepsy, significant neurological disorders, depression, suicidal ideation and behaviour, cerebrovascular attacks or ischemia History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy Evidence of severe renal dysfunction defined as: eGFR < 30 ml/min/1,73 m2 (calculated using the MDRD formula) at screening (Visit 1) 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) History of lymphoproliferative disorders Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits 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. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins) Inability or unwillingness to undergo repeated punch biopsies History of allergy to any component of the study medication Current use of strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin and St John's wort) Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption Evidence of acute contact dermatitis at screening Evidence of underweight, defined as BMI < 18,5 kg/m2 Evidence of Zink deficiency defined as Zink level < 20 µg/dL in serum

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kilian Eyerich

Organizational Affiliation

Technical University Munich

Official's Role

Principal Investigator

Facility Information:

Facility Name

Technical University Munich - Department of Dermatology

City

Munich

State/Province

Bavaria

ZIP/Postal Code

80805

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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