Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4

NCT ID: NCT03556592

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-13
• Study Completion Date: 2020-06-20

Brief Summary

The purpose of this trial is to investigate if tralokinumab changes the metabolism of selected CYP substrates in adults with moderate-to-severe AD after:

• 14 weeks of treatment with tralokinumab
• a single dose of tralokinumab

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All subjects

Tralokinumab - investigational medicinal product:

Week 0: subcutaneous (SC) injection of tralokinumab loading dose.

Week 2 to Week 14: SC injection of tralokinumab maintenance dose.

CYP substrates - non-investigational medicinal products:

Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.

Group Type: EXPERIMENTAL

Tralokinumab

Intervention Type: DRUG

Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection.

Caffeine

Intervention Type: DRUG

1x 100 mg tablet

Warfarin

Intervention Type: DRUG

2x 5 mg tablets

Omeprazole

Intervention Type: DRUG

1x 20 mg capsule

Metoprolol

Intervention Type: DRUG

1x 100 mg tablet

Midazolam Hydrochloride

Intervention Type: DRUG

1 mL of 2 mg/mL oral solution/syrup

Interventions

Tralokinumab

Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection.

Intervention Type: DRUG

Caffeine

1x 100 mg tablet

Intervention Type: DRUG

Warfarin

2x 5 mg tablets

Intervention Type: DRUG

Omeprazole

1x 20 mg capsule

Intervention Type: DRUG

Metoprolol

1x 100 mg tablet

Intervention Type: DRUG

Midazolam Hydrochloride

1 mL of 2 mg/mL oral solution/syrup

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 and above.
• Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD.
• History of AD for ≥1 year.
• Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable.
• AD involvement of ≥10% body surface area at screening and baseline.
• Stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline.
• Willingness to abstain from consumption of any 1 or more of the following items in the periods specified:

• ±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:

• Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.
• Cruciferous vegetables (for example broccoli).
• Chargrilled meat.
• ±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.

Exclusion Criteria

• Administration, within 14 days or 5 half-lives (whichever is longer) prior to Day -7, of any medication that is a known inducer or inhibitor of 1 or more of the following CYP enzymes: CYP3A, CYP2C19, CYP2C9, CYD2D6, and CYP1A2.
• Subjects who are poor metabolisers of CYP2C9, CYP2C19, or CYP2D6, based on genotyping.
• Any contraindication to 1 or more of the following drugs, according to the applicable labelling: caffeine, warfarin, omeprazole, metoprolol, or midazolam.
• Consumption of any 1 or more of the following items in the periods specified:

• ±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:

• Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.
• Cruciferous vegetables (for example broccoli).
• Chargrilled meat.
• ±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.
• Nausea or diarrhoea 1 week prior to Day -7.
• Active dermatologic conditions that may confound the diagnosis of AD.
• Use of tanning beds or phototherapy within 5 weeks prior to Day -7.
• Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 3 weeks prior to Day -7.
• Treatment with topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors within 1 week prior to Day -7.
• Receipt of any marketed biological therapy or investigational biologic agent (including immunoglobulin, anti-IgE, or dupilumab):

• Any cell-depleting agents, including but not limited to rituximab: within 6 months prior to Day -7, or until lymphocyte count returns to normal, whichever is longer.
• Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to Day -7.
• Active skin infection within 1 week prior to Day -7.
• Clinically significant infection within 4 weeks prior to Day -7.
• A helminth parasitic infection within 6 months prior to the date informed consent is obtained.
• Tuberculosis requiring treatment within 12 months prior to screening.
• Known primary immunodeficiency disorder.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LEO Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical expert

Role: STUDY_DIRECTOR

LEO Pharma

Locations

LEO Pharma Investigational Site

Little Rock, Arkansas, United States

LEO Pharma Investigational Site

Rogers, Arkansas, United States

LEO Pharma Investigational Site

San Diego, California, United States

LEO Pharma Investigational Site

Doral, Florida, United States

LEO Pharma Investigational Site

Miami, Florida, United States

LEO Pharma Investigational Site

Miami, Florida, United States

LEO Pharma Investigational Site

Quincy, Massachusetts, United States

LEO Pharma Investigational Site

Spartanburg, South Carolina, United States

LEO Pharma Investigational Site

Norfolk, Virginia, United States

LEO Pharma Investigational Site

Nice, , France

LEO Pharma Investigational Site

Paris, , France

LEO Pharma Investigational Site

Leiden, , Netherlands

Countries

United States; France; Netherlands

Other Identifiers

2018-000534-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LP0162-1342

Identifier Type: -

Identifier Source: org_study_id