A Study of Intravenous MK-8226 in Participants With Moderate-to-Severe Atopic Dermatitis (MK-8226-003)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Atopic Dermatitis

Treatments: Drug: MK-8226; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01732510

8226-003

2012-005560-95 (EudraCT Number)

Details and patient eligibility

About

This is a 3-part study to assess the safety, tolerability, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MK-8226 in participants with moderate to severe atopic dermatitis. Part 1 (multiple rising dose study) objectives were to find the maximum tolerated dose (MTD) of MK-8226 and to assess safety and PK. Part 2 objectives were to determine safety, PK, and preliminary efficacy. Part 3 objectives were to further define safety and PK, and explore MK-8226 PK/PD to model the optimal dose range for future studies. The study was terminated early due to business reasons on 08 May 2014; final results from an analysis for Part 1 (efficacy, PK, safety, immunogenicity) and Part 2 (safety, immunogenicity) are summarized.

Full description

Part 1 of the study is a multiple rising dose assessment of the safety, tolerability, and pharmacokinetics of MK-8226 for a period of 12 weeks followed by a 20-week off-treatment follow-up period.

Part 2 of the study is an assessment of the safety, tolerability, and efficacy of MK-8226 for 12 weeks followed by a 20-week off-treatment follow-up period.

In Part 3 of the study, participants will be treated with MK-8226 for a period of 12 weeks followed by a 20-week off-treatment follow-up period to evaluate pharmacokinetic and pharmacokinetic correlations to assist with modeling the dose range planned for further studies.

Enrollment: 65 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body weight >=40 kg
• Clinical diagnosis of atopic dermatitis for at least 6 months prior
• Candidate for systemic or phototherapy (i.e., failed topical treatment)
• Moderate-to-severe disease as defined by Body Surface Area (BSA) ≥10%, EASI ≥12, and IGA ≥3
• No clinically significant abnormality on electrocardiogram
• No history of active or latent tuberculosis (TB) and no signs or symptoms suggestive of TB
• No history of active or latent TB and no signs or symptoms suggestive of TB
• History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors within 3 months before the screening visit

Exclusion criteria

• Concurrent significant skin disease
• Any significant organ dysfunction within 6 months prior
• History of clinically significant heart disease
• History of neoplastic disease
• Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
• Infection requiring oral antibiotics within 2 weeks prior
• Receipt of a live virus vaccine within 4 weeks prior
• Inability to refrain from topical or systemic therapy during course of the study
• Had major surgery or donated or lost >=1 unit of blood within 4 weeks prior
• Participation in another study within 4 weeks prior
• Current or regular user of illicit drugs or a history of drug or alcohol abuse within 1 year prior
• Pregnant, breast-feeding, or anticipated to conceive during the course of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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65 participants in 7 patient groups, including a placebo group

Part 1: MK-8226 0.3 mg/kg

Experimental group

Description:

MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks.

Treatment:

Drug: MK-8226

Part 1: MK-8226 1 mg/kg

Experimental group

Description:

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Treatment:

Drug: MK-8226

Part 1: MK-8226 3 mg/kg

Experimental group

Description:

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Treatment:

Drug: MK-8226

Part 1: MK-8226 10 mg/kg

Experimental group

Description:

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Treatment:

Drug: MK-8226

Part 1: Placebo (pooled)

Placebo Comparator group

Description:

Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks.

Treatment:

Drug: Placebo

Part 2: MK-8226 3 mg/kg

Experimental group

Description:

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Treatment:

Drug: MK-8226

Part 2: Placebo

Placebo Comparator group

Description:

Placebo administered IV every 2 weeks for a period of 12 weeks.

Treatment:

Drug: Placebo