Clinical trial NCT01732510: A Study of Intravenous MK-8226 in Participants With Moderate-to-Severe Atopic Dermatitis (MK-8226-003)
Official title: A Phase Ib Randomized, Double-Blinded, Placebo-Controlled Multiple Rising Dose Clinical Trial to Evaluate the Safety, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Intravenous MK-8226 in Patients With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-11-22
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced at Least One Adverse Event
timeFrame: Up to 32 Weeks
measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to 12 Weeks
measure: Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2
timeFrame: Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16
measure: Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2
timeFrame: Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16
measure: Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration
timeFrame: Days 1, 3, 5, 9, 14, 70, 72, 74, 84
measure: AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration
timeFrame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
measure: Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration
timeFrame: Days 1, 3, 5, 9, 14, 70, 72, 74, 84
measure: Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration
timeFrame: Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84
measure: Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration
timeFrame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
measure: Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration
timeFrame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
measure: Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2
timeFrame: Baseline, Week 4, Week 8, Week 24
measure: Percentage of Participants With an Investigator Global Assessment (IGA) Score of Clear or Almost Clear in Study Part 2
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24
measure: Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2
timeFrame: Baseline, Week 4, Week 12, Week 24
measure: Change From Baseline in Participant Pruritus in Study Part 2
timeFrame: Baseline, Week 4, Week 12, Week 24
measure: Change From Baseline in Participant Sleep Disturbance in Study Part 2
timeFrame: Baseline, Week 4, Week 12, Week 24
measure: Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2
timeFrame: Up to Week 12
measure: Percentage of Participants With >=50% Improvement in EASI Score
timeFrame: Baseline, Week 12, Week 24
measure: Number of Participants Positive for Anti-Drug Antibody (ADA) Formation
timeFrame: Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224
Other outcomes:
measure: Change From Baseline in the Participant's Global Impression of Disease Status in Study Part 2
timeFrame: Baseline, Week 4, Week 12, Week 24
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: