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

Phase 1
Completed
Conditions
Dermatitis, Atopic
Interventions
Biological: Placebo
Registration Number
NCT05450198
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
72
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Expansion Panel EPlaceboParticipants are randomized to a dose less than or equal to high dose MK-6194 or placebo administered q2w.
Expansion Dose FPlaceboParticipants are randomized to a dose less than or equal to high dose MK-6194 or placebo q2w.
Dose Escalation Panel AMK-6194Participants are randomized to low dose MK-6194 or placebo, administered every 2 weeks (q2w).
Dose Escalation Panel APlaceboParticipants are randomized to low dose MK-6194 or placebo, administered every 2 weeks (q2w).
Dose Escalation Panel BMK-6194Participants are randomized to medium dose MK-6194 or placebo administered q2w.
Dose Escalation Panel BPlaceboParticipants are randomized to medium dose MK-6194 or placebo administered q2w.
Dose Escalation Panel CMK-6194Participants are randomized to high dose MK-6194 or placebo administered q2w.
Dose Escalation Panel CPlaceboParticipants are randomized to high dose MK-6194 or placebo administered q2w.
Expansion Panel DMK-6194Participants are randomized to medium dose MK-6194 or placebo administered q2w.
Expansion Panel DPlaceboParticipants are randomized to medium dose MK-6194 or placebo administered q2w.
Expansion Panel EMK-6194Participants are randomized to a dose less than or equal to high dose MK-6194 or placebo administered q2w.
Expansion Dose FMK-6194Participants are randomized to a dose less than or equal to high dose MK-6194 or placebo q2w.
Primary Outcome Measures
NameTimeMethod
Number of Participants Who Experience One or More Adverse Events (AEs)Up to approximately 169 days

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. The number of participants who experienced an AE is presented.

Number of Participants Who Discontinue Study Intervention Due to an AEUp to approximately 85 days

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. The number of participants who discontinued study intervention due to an AE is presented.

Secondary Outcome Measures
NameTimeMethod
Area Under the Curve (AUC) From Days 1-15 (AUC1-15) of MK-6194Day 1 (Predose and 12 hours postdose), Day 8, and Day 15

Blood samples were collected at pre-specified time points to determine the AUC1-15 of MK-6194 in plasma.

AUC From Days 29-43 (AUC29-43) of MK-6194Day 29 (Predose and 12 hours postdose), Day 36, and Day 43

Blood samples were collected at pre-specified time points to determine the AUC29-43 of MK-6194 in plasma.

Peak Serum Concentration (Cmax) of MK-6194 (Day 1 to 29)Day 1 (Predose and 12 hours postdose), Day 8, Day 15, and Day 29 (Predose and 12 hours postdose)

Blood samples were collected at pre-specified time points to determine the Cmax of MK-6194 in plasma.

Minimum Serum Concentration (Ctrough) of MK-6194 (Day 1 to 29)Predose on Days 15 and 29

Blood samples were collected at pre-specified time points to determine the Ctrough of MK-6194 in plasma.

Time to Peak Serum Concentration (Tmax) of MK-6194 (Day 1 to 29)Day 1 (Predose and 12 hours postdose), Day 8, Day 15, and Day 29 (Predose and 12 hours postdose)

Blood samples were collected at pre-specified time points to determine the Tmax of MK-6194 in plasma.

Geometric Mean Accumulation Ratio of AUC of MK-6194Day 1 (Predose and 12 hours postdose), Day 8, Day 15, Day 29 (Predose and 12 hours postdose), Day 36, and Day 43

Blood samples were collected at pre-specified time points to determine the geometric mean accumulation ratio of AUC of MK-6194. The accumulation ratio is defined as Day 29-43/ Day 1-15.

Geometric Mean Accumulation Ratio of Cmax of MK-6194Day 1 (Predose and 12 hours postdose), Day 8, Day 15, Day 29 (Predose and 12 hours postdose), Day 36, and Day 43

Blood samples were collected at pre-specified time points to determine the geometric mean accumulation ratio of Cmax of MK-6194. The accumulation ratio is defined as Day 29-43/ Day 1-15.

Fold Change From Baseline in Peak Regulatory T Cells (Tregs)Baseline and Day 85

Blood samples were collected to determine the fold change from baseline (FCB) in peak Tregs. The peak Treg FCB was evaluated after the last dose of MK-6194 on Day 85 using natural-log transformed values with a linear model containing fixed effects.

Trial Locations

Locations (19)

AXIS Clinicals ( Site 0029)

🇺🇸

Dilworth, Minnesota, United States

Innovaderm Research Inc. ( Site 0019)

🇨🇦

Montréal, Quebec, Canada

Progressive Clinical Research ( Site 0022)

🇺🇸

San Antonio, Texas, United States

North Texas Center for Clinical Research ( Site 0028)

🇺🇸

Frisco, Texas, United States

Genesis Clinical Research, LLC ( Site 0004)

🇺🇸

Tampa, Florida, United States

ForCare Clinical Research ( Site 0003)

🇺🇸

Tampa, Florida, United States

Advanced Medical Research, PC. ( Site 0027)

🇺🇸

Sandy Springs, Georgia, United States

Premier Clinical Research ( Site 0026)

🇺🇸

Spokane, Washington, United States

Miami Dermatology and Laser Research ( Site 0025)

🇺🇸

Miami, Florida, United States

Global Health Research Center, Inc. ( Site 0005)

🇺🇸

Miami Lakes, Florida, United States

Remington Davis Clinical Research ( Site 0021)

🇺🇸

Columbus, Ohio, United States

Paddington Testing Company ( Site 0010)

🇺🇸

Philadelphia, Pennsylvania, United States

Complete Dermatology ( Site 0023)

🇺🇸

Sugar Land, Texas, United States

Anima ( Site 0013)

🇧🇪

Alken, Limburg, Belgium

Arkansas Research Trials-Clinical Trials ( Site 0002)

🇺🇸

North Little Rock, Arkansas, United States

ARENSIA Exploratory Medicine-SC ARENSIA Exploratory Medicine SRL with Monza Medical Center ( Site 00

🇷🇴

Bucharest, Bucuresti, Romania

ARENSIA Exploratory Medicine-Country Emergency Hospital- Arensia,Cluj-Napoca ( Site 0017)

🇷🇴

Cluj-Napoca, Cluj, Romania

ARENSIA Exploratory Medicine - Sofia ( Site 0018)

🇧🇬

Sofia, Sofia (stolitsa), Bulgaria

Hospital Germans Trias i Pujol-CCEE Dermatologia ( Site 0012)

🇪🇸

Badalona, Barcelona, Spain

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