A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety deucravacitinib in patients with chronic hand eczema (investigator-sponsored research)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

18 Jul 2024 → 7 Nov 2025

Decision date (initial)

2023-11-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of daily application of 6 mg BID deucravacitinib compared with a placebo in the treatment of adult subjects with chronic hand eczema.

Secondary objectives 1

1. To evaluate the health-related quality of life and safety of daily application of 6 mg BID deucravacitinib compared with a placebo in the treatment of adult subjects with chronic hand eczema.

Conditions and MedDRA coding

Chronic Hand Eczema

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients must have signed and dated an IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines before the performance of any protocol-related procedures
2. Patients with diagnosis of chronic hand eczema (persisted > 3 months or returned twice or more within the past 12 months)
3. Patients with moderate to severe disease and Investigator Global Assessment (IGA) score ≥ 3 (scale of 0 to 4) at screening and baseline visit.
4. Patients with failed topical therapy for 6 weeks will be included and patients should be eligible for a systemic therapy
5. Male or female patients aged 18 to 65 years old
6. Patients with BMI (body mass index) of ca. 18-35 kg/m2
7. Patients able to provide written informed consent
8. Patient willing and able to comply with clinic visits and study related procedures

Exclusion criteria 29

1. Diagnosis of any concurrent skin disease on the hands, e.g. tinea manuum
2. Evidence of chronic kidney disease with an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or if subject is receiving dialysis
3. On current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis, or hepatic failure, or has evidence of liver disease as indicated by persistent (confirmed by repeated tests ≥ 2 weeks apart) elevated transaminases (ala-nine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 2.5 times the upper limit of normal (ULN) during the screening period
4. Patients with a current or history of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphade-nopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for less than 5 years: a) Patients with cervical carcinoma in situ that has been appropriately treated with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study. b) Patients with basal cell or squamous epithelial skin cancers that have been appropriately treated with no evidence of recurrence for at least 3 years may participate in the study
5. History of allergy to any component of the study medication
6. History of alcohol or drug abuse within 2 years before the screening visit
7. Known history of human immunodeficiency virus (HIV) infection or HIV seropositivity
8. Current diagnosis of hepatitis B viral infection at the time of screening as evidenced by a) Positive hepatitis B surface antigen (HBsAg) OR b) Positive total hepatitis B core antibody (HBcAb) confirmed by positive HBV DNA
9. Current diagnosis of hepatitis C viral infection at the time of screening as evidence by a) Positive HCV Ab AND b) Positive HCV RNA
10. Patients who have any of the following specific abnormalities on screening laboratory tests: a) hemoglobin <10.0 g/dL (100.0 g/L), b) total white blood cell count <2500 cells/µL, c) neutropelymphonia (absolute neutrophil count [ANC] <1000 cells/µL), d) penia (lymphocyte count <750 cells/µL), e) thrombocytopenia (platelets <100,000/µL), f) alkaline phosphatase >3x upper limit of normal (ULN) or alkaline phosphatase >2,5x ULN and total bilirubin > 2x ULN, g) aspartate transaminase (AST, SGOT) and alanine transaminase (ALT, SGPT) > 2.5x upper limit of normal (ULN)
11. Treatment with any of the following agents: Janus kinase inhibitors, immunosuppres-sive/immunomodulating drugs including but not limited to methotrexate, azathioprine, dapsone, leflunomide, mycophenolate-mofetil; retinoids (e.g. alitretinoin); cyclospor-ine; sulphasalasine, hy-droxychloroquine sulphate, TNF-alpha inhibitors (etaner-cept, adalimumab, alefacept), colchicine, and IFN-γ within 1 month prior to screening.
12. Active AD requiring medical treatment in regions other than the hands
13. Diagnosis of tuberculosis (TB) with a positive QuantiFER-ON-TB Gold Plus test or high TB risk after assessment of recent close or prolonged contact with someone with in-fectios TB disease (defined as within the last 12 months) and/or recent travel to or from a high burden country of TB (as listed by the WHO, https://www.who.int/news/item/17-06-2021-who-releases-new-global-lists-of-high-burden-countries-for-tb-hiv-associated-tb-and-drug-resistant-tb)
14. Use of systemic antibiotics or cutaneously applied antibiotics on the hands within 14 days prior to baseline
15. Use of a live vaccine 90 days prior to screening, or during this study
16. Patients, who are older than 50 years and do not have a vaccination against Herpes zoster
17. Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit
18. Subject is currently enrolled in another investigational device or drug trial(s), has re-ceived investigational drug within 90 days before baseline visit
19. Pregnant or breastfeeding women or planning to become pregnant or breastfeed during the patient’s participation in this study
20. Women of childbearing potential (WOCBP) who are unwilling to practice highly effec-tive contraception prior to the initial dose/start of the first treatment, during the study, and for at least 30 days after the last dose.
21. Potential subjects who are in a dependent/employment relationship with the sponsor, investigator or clinical trial site.
22. Active psoriasis or severe acneiforme skin disease on any part of the body
23. Potential subjects who are placed in an institution due to a court or official order
24. Presence of skin comorbidities that may interfere with the study assessments
25. Clinically significant infection (e.g. impetiginised hand eczema) on the hands
26. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely af-fect the patient’s participation in the study. Patients with uncontrolled diabetes (HbA1c ≥ 9%), patients with cardiovascular conditions including stage III or IV cardiac failure according to the New York Heart Association classification (recent cerebrovascular accidents, myocardial infarction, coronary stenting or moderate to severe congestive heart failure), severe renal conditions (eg, patients on dialysis), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (eg, Eosinophilic granulomatosis with polyangitis (EGPA), lupus, inflammatory bowel disease, rheuma-toid arthritis, etc.), other severe endocrinological, gastrointestinal, hepatobiliary (e.g. Pugh type C, severe liver insufficiency), metabolic, pulmonary or lymphatic diseases
27. History or presence of epilepsy, significant neurological disorders, severe depression, suicidal ideation and behavior, cerebrovascular attacks or ischemia
28. Patients with an active, severe infection in anamnesis and a chronic infection should be excluded from the clinical trial
29. Presence of myocardial infarction (within the last 3 months) or cardiac arrhythmia requiring drug therapy in combination with a general increased risk of cardiovascular disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Therapeutic efficacy of deucravacitinib defined as the percentage of patients achieving a clinical response (Investigator Global Assessment 0 or 1) with ≥ 2-point improvement in IGA for patients with chronic hand eczema at week 16

Secondary endpoints 6

1. Participant self-assessment (PSA) [Time Frame: Baseline, week 2, 4, 6, 8, 12 and 16]
2. Quality of Life in Hand Eczema Questionnaire (QOLHEQ) [Time Frame: Baseline; Week 4, 8, 16]
3. Hand eczema severity index (HECSI) [Time Frame: Baseline; Week 4, 8, 16]
4. Evaluation of safety in terms of number of AE and lab parameters
5. Change in skin physiology from baseline to week 16
6. Change in histology, in expression of skin barrier proteins, expression of cytokines, in extent of immune cells in skin biopsies, and the transcriptome from baseline to week 16

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Chariteplatz 1, Mitte Mitte

City

Berlin

Postcode

10117

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Philipp Globig

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Philipp Globig

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Corrective measures 1 · Art. 77 CTR

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