An investigator-initiated, multi-center, randomized, double-blind, placebo controlled study of Dupilumab to demonstrate efficacy in subjects with nummular eczema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum rechts der Isar der TU Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

15 Mar 2021 → 1 Sep 2025

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515534-32-00

EudraCT number

2019-003162-41

ClinicalTrials.gov

NCT04600362

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of Dupilumab in patients with nummular eczema.

Secondary objectives 1

1. To asses improvement (Decrease) of disease.

Conditions and MedDRA coding

Subjects with nummular eczema

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Clinically confirmed diagnosis of NE
2. Biopsy-proven, meaning histology consistent with eczema (including PAS-staining).
3. EASI score ≥ 10.
4. PGA ≥ 3 on a 5 point scale.
5. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
6. Female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at screening. This includes: A woman who is not capable of bearing a child is defined as follows: post-menopausal (12 months natural (spontaneous) amenorrhea or 6 months spontaneous amenorrhea with serum-FSH-values (follicle-stimulating hormone) of >40 mIU/mL); 6 weeks after a bilateral ovariectomy with or without hysterectomy or sterilization by means of tubal ligation A woman capable of bearing child is defined as follows: a woman who is physiologically capable of becoming pregnant, including women whose occupation, lifestyle or sexual orientation exclude sexual intercourse with a male partner and women whose partners have been sterilized by vasectomy or other measures. Medically-approved methods of contraception can include the following: hormonal contraceptives or intrauterine device. Acceptable preventive measures can include total abstinence at the discretion of the investigator, in cases where compliance is ensured because of the study participant’s age, occupation, lifestyle or sexual orientation. Periodical abstinence (e.g. calendar, ovulation, symptothermal methods or abstinence until the 4th day after the ovulation) as well as coitus interruptus are not acceptable methods of contraception. Effective contraception (CTFG guideline) for women of childbearing potential should be used throughout the study, including during the follow-up period or at least 120 days after last dose, whichever is longer (elapse of 4-5 half-lives). The event of pregnancy, Dupilumab should be immediately discontinued.
7. History of continuous use of at least mid-potency topical steroids for the last 8 weeks.
8. Age 18-85 years of age, body weight ≥ 40 kg and ≤ 160 kg.
9. Signed informed consent from patient.

Exclusion criteria 27

1. Permanent severe diseases, especially those affecting the immune system.
2. Known history of human immunodeficiency virus (HIV) infection.
3. Established diagnosis of Hepatitis B viral infection at the time of screening.
4. Pregnancy or breast feeding.
5. Established diagnosis of hepatitis C viral infection at the time of screening.
6. History of past or current tuberculosis or other mycobacterial infection.
7. Presence of skin comorbidities that may interfere with study assessments. This includes, but is not limited to, conditions like scabies, seborrheic dermatitis, Cutaneous T cell Lymphoma, Psoriasis, etc.
8. Malignancy within 5 years of the screening visit excluding local cutaneous squamous cell
9. Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study. Examples include, but are not limited to patients with short life expectancy, patients with major congenital malformations, patients with cardiovascular conditions (eg, major, clinically significant congenital cardiovascular abnormalities), severe renal conditions, hepato-biliary conditions (eg, Child-Pugh class B or C), active major autoimmune diseases (eg, lupus, inflammatory bowel disease etc.), other severe endocrinological, gastrointestinal, metabolic, pulmonary, neurological or lymphatic diseases. The specific justification for patients excluded under this criterion will be noted in study documents (chart notes, case report forms [CRF], etc).
10. Any other medical or psychological condition including relevant laboratory abnormalities at screening that, in the opinion of the investigator, suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical trial, may make patient's participation unreliable, or may interfere with study assessments. The specific justification for patients excluded under this criterion will be noted in study documents (chart notes, CRF, etc).
11. Planned major surgical procedure during the patient's participation in this study.
12. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins).
13. Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit, independent from of the cuntaneous dysbiosis found in NE.
14. Treatment with an investigational drug within 8 weeks before the baseline visit*.
15. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
16. Diagnosed active endoparasitic infections or at high risk of these infections.
17. Evidence of severe renal dysfunction defined as: eGFR < 30 ml/min/1,73 m^2 (calculated using the cockroft gault formula f) at screening (Visit 1)
18. 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).
19. Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits.
20. Inability or unwillingness to undergo repeated punch biopsies.
21. History of allergy to any component of the study medication.
22. Evidence of acute contact dermatitis at screening.
23. Evidence of Zink deficiency defined as Zink level < 20 µg/dL in serum.
24. History of important side effects of medium potency topical corticosteroids (eg, intolerance to treatment, hypersensitivity reactions*, significant skin atrophy, systemic effects), as assessed by the investigator or patient’s treating physician.
25. ≥30% of the total lesional surface located on areas of thin skin that cannot be safely treated with medium potency TCS (eg, face, neck, intertriginous areas, genital areas, areas of skin atrophy) at baseline.
26. Planned or anticipated use of any prohibited medications and procedures during study treatment.
27. * Participation in a prior clinical trial is permitted, as long as adequate wash-out periods and exclusion criterion #4 are taken into consideration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in EASI score from baseline to week 16

Secondary endpoints 7

1. Number of Patients Achieving an Improvement (Decrease) in Physician Global Assessment (PGA) 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.
2. Eczema Area and Severity Index (EASI) 50 score at week 16 The proportion of subjects who achieve at least a 50% reduction in the EASI score at Week 16 compared to week 0 (Baseline).
3. 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.
4. Change from Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16.
5. Change from Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16.
6. Change from Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 16.
7. Safety of Dupilumab will be assessed by Evaluating Adverse Events (AEs).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum rechts der Isar der TU Muenchen AöR

Sponsor organisation

Klinikum rechts der Isar der TU Muenchen AöR

Address

Ismaninger Strasse 22, Au-Haidhausen Au-Haidhausen

City

Munich

Postcode

81675

Country

Germany

Scientific contact point

Organisation

Klinikum rechts der Isar der TU Muenchen AöR

Contact name

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein

Public contact point

Organisation

Klinikum rechts der Isar der TU Muenchen AöR

Contact name

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications