Multiple Rising Dose Study of MK-6194 in Participants With Atopic Dermatitis (MK-6194-008)

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to characterize the safety and tolerability of MK-6194 following multiple doses among participants with moderate to severe atopic dermatitis who are unresponsive to other therapies.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-6194 in Participants With Moderate to Severe Atopic Dermatitis

Conditions
-----------------
Dermatitis, Atopic

Intervention / Treatment
-----------------
* Biological: MK-6194
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Clinical diagnosis of atopic dermatitis for at least 6 months prior to the Screening visit. Atopic dermatitis is of at least moderate severity. History of inadequate response to a stable (≥1 month) regimen of medium to high potency topical corticosteroids or calcineurin inhibitors as treatment for atopic dermatitis within 6 months before the screening visit. Body Mass Index (BMI) ≥18 and ≤38 kg/m2 at the screening visit. Exclusion Criteria: Concurrent significant skin disease other than atopic dermatitis (such as psoriasis) or a concurrent clinically significant disease. Significant organ dysfunction that is unstable or inadequately treated within 6 months prior to Screening. History of cancer (malignancy), with the exceptions: of adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; other malignancies that have been successfully treated with appropriate follow up. History of myocardial infarction, congestive heart failure, uncontrolled arrhythmias, cardiac revascularization, stroke, uncontrolled hypertension, or uncontrolled diabetes within 6 months of Screening. History of organ or tissue allograft. History of symptomatic herpes zoster within 16 weeks of randomization, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or central nervous system (CNS) zoster. Major surgery within 3 months prior to the screening visit or has a major surgery planned during the study. Received a live or attenuated virus vaccine within 4 weeks prior to the Screening visit or intends to receive live or attenuated virus vaccination during the course of the study and for 12 weeks after the last dose of study drug. Currently receiving any chronic systemic (oral or intravenous) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Panel A<br>Participants are randomized to low dose MK-6194 or placebo, administered every 2 weeks (q2w). | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|
| Experimental: Dose Escalation Panel B<br>Participants are randomized to medium dose MK-6194 or placebo administered q2w. | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|
| Experimental: Dose Escalation Panel C<br>Participants are randomized to high dose MK-6194 or placebo administered q2w. | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|
| Experimental: Expansion Panel D<br>Participants are randomized to medium dose MK-6194 or placebo administered q2w. | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|
| Experimental: Expansion Panel E<br>Participants are randomized to a dose less than or equal to high dose MK-6194 or placebo administered q2w. | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|
| Experimental: Expansion Dose F<br>Participants are randomized to a dose less than or equal to high dose MK-6194 or placebo q2w. | Biological: MK-6194<br>* MK-6194 administered subcutaneously (SC)<br>Biological: Placebo<br>* Placebo comparator to MK-6194 administered SC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience One or More Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 169 days | 
| Number of Participants who Discontinue Study Intervention Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) from Days 1-15 (AUC1-15) of MK-6194 | Blood samples will be collected at pre-specified time points to determine the AUC1-15 of MK-6194 in plasma. | At protocol specific time points from Day 1 to Day 15 | 
| AUC from Days 29-43 (AUC29-43) of MK-6194 | Blood samples will be collected at pre-specified time points to determine the AUC29-43 of MK-6194 in plasma. | At protocol specific time points from Day 29 to Day 43 | 
| Peak Serum Concentration (Cmax) of MK-6194 | Blood samples will be collected at pre-specified time points to determine the Cmax of MK-6194 in plasma. | At protocol specific time points from Day 1 to Day 29 | 
| Minimum Serum Concentration (Ctrough) of MK-6194 | Blood samples will be collected at pre-specified time points to determine the Ctrough of MK-6194 in plasma. | Days 15, 29, 43, and 85: Predose | 
| Time to peak Serum Concentration (Tmax) of MK-6194 | Blood samples will be collected at pre-specified time points to determine the Tmax of MK-6194 in plasma. | At protocol specific time points from Day 1 to Day 29 | 
| Geometric Mean Accumulation Ratio of AUC of MK-6194 | Blood samples will be collected at pre-specified time points to determine the geometric mean accumulation ratio of AUC of MK-6194. | At protocol specific time points from Day 1 to Day 15 and Day 29 to Day 43 | 
| Geometric Mean Accumulation Ratio of Cmax of MK-6194 | Blood samples will be collected at pre-specified time points to determine the geometric mean accumulation ratio of Cmax of MK-6194. | At protocol specific time points from Day 1 to Day 15 and Day 29 to Day 43 | 
| Fold Change from Baseline in Peak Regulatory T cells (Tregs) | Blood samples will be collected at baseline and at pre-specified timepoints up to day 169 to determine the fold change from baseline in peak Tregs. | Baseline and up to approximately 169 days |