Dermatitis, Atopic
Conditions
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.
Interventions
BIOLOGICALMK-6194
MK-6194 administered subcutaneously (SC)
BIOLOGICALPlacebo
Placebo comparator to MK-6194 administered SC
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 AE | Up 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
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Accumulation Ratio of AUC of MK-6194 | Day 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. |
| Area Under the Curve (AUC) From Days 1-15 (AUC1-15) of MK-6194 | Day 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-6194 | Day 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. |
| 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 Cmax of MK-6194 | Day 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. |
| 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. |
Countries
Belgium, Bulgaria, Canada, Romania, Spain, United States
Participant flow
Pre-assignment details
Participants were enrolled in this study and received MK-6194 or Placebo in Panels A through F. Panels were pre-specified in the protocol to be pooled at dose group level. The exact dose value is proprietary, and directionality is provided.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered subcutaneously (SC) every 2 weeks (Q2W) in Panels A, B, C, D, E for 7 doses, or every 4 weeks (Q4W) in Panel F for 4 doses. | 18 |
| MK-6194 Low Dose (Panel A) Participants received low dose of MK-6194 administered SC Q2W for 7 doses. | 6 |
| MK-6194 High Dose (Panel B-E) Participants received high dose of MK-6194 administered SC Q2W for 7 doses. The dose was the same in Panels B-E and F. | 36 |
| MK-6194 High Dose (Panel F) Participants received high dose of MK-6194 administered SC Q4W for 4 doses. The dose was the same in Panels B-E and F. | 12 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | MK-6194 Low Dose (Panel A) | MK-6194 High Dose (Panel B-E) | MK-6194 High Dose (Panel F) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.2 Years STANDARD_DEVIATION 11 | 46.5 Years STANDARD_DEVIATION 11.3 | 42.8 Years STANDARD_DEVIATION 16.8 | 42.0 Years STANDARD_DEVIATION 16.5 | 41.6 Years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 6 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 6 Participants | 30 Participants | 11 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 6 Participants | 31 Participants | 10 Participants | 61 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 18 Participants | 5 Participants | 30 Participants |
| Sex: Female, Male Male | 13 Participants | 4 Participants | 18 Participants | 7 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 | 0 / 36 | 0 / 12 | 0 / 54 |
| other Total, other adverse events | 13 / 18 | 6 / 6 | 30 / 36 | 9 / 12 | 45 / 54 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 | 2 / 36 | 0 / 12 | 2 / 54 |
Outcome results
Primary
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. The number of participants who discontinued study intervention due to an AE is presented.
Time frame: Up to approximately 85 days
Population: The analysis population consisted of all participants who received ≥1 dose of study intervention. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Discontinue Study Intervention Due to an AE | 0 Participants |
| MK-6194 Low Dose (Panel A) | Number of Participants Who Discontinue Study Intervention Due to an AE | 1 Participants |
| MK-6194 High Dose (Panel B-E) | Number of Participants Who Discontinue Study Intervention Due to an AE | 2 Participants |
| MK-6194 High Dose (Panel F) | Number of Participants Who Discontinue Study Intervention Due to an AE | 0 Participants |
| MK-6194 Total | Number of Participants Who Discontinue Study Intervention Due to an AE | 3 Participants |
Primary
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. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 169 days
Population: The analysis population consisted of all participants who received ≥1 dose of study intervention. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experience One or More Adverse Events (AEs) | 13 Participants |
| MK-6194 Low Dose (Panel A) | Number of Participants Who Experience One or More Adverse Events (AEs) | 6 Participants |
| MK-6194 High Dose (Panel B-E) | Number of Participants Who Experience One or More Adverse Events (AEs) | 30 Participants |
| MK-6194 High Dose (Panel F) | Number of Participants Who Experience One or More Adverse Events (AEs) | 9 Participants |
| MK-6194 Total | Number of Participants Who Experience One or More Adverse Events (AEs) | 45 Participants |
Secondary
Area Under the Curve (AUC) From Days 1-15 (AUC1-15) of MK-6194
Blood samples were collected at pre-specified time points to determine the AUC1-15 of MK-6194 in plasma.
Time frame: Day 1 (Predose and 12 hours postdose), Day 8, and Day 15
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the lower limit of quantification (BLQ) or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | Area Under the Curve (AUC) From Days 1-15 (AUC1-15) of MK-6194 | 32.3 day*ng/mL |
| MK-6194 High Dose (Panel B-E) | Area Under the Curve (AUC) From Days 1-15 (AUC1-15) of MK-6194 | 59.6 day*ng/mL |
Secondary
AUC From Days 29-43 (AUC29-43) of MK-6194
Blood samples were collected at pre-specified time points to determine the AUC29-43 of MK-6194 in plasma.
Time frame: Day 29 (Predose and 12 hours postdose), Day 36, and Day 43
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the BLQ or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | AUC From Days 29-43 (AUC29-43) of MK-6194 | 10.9 day*ng/mL |
| MK-6194 High Dose (Panel B-E) | AUC From Days 29-43 (AUC29-43) of MK-6194 | 56.7 day*ng/mL |
| MK-6194 High Dose (Panel F) | AUC From Days 29-43 (AUC29-43) of MK-6194 | 86.7 day*ng/mL |
Secondary
Fold Change From Baseline in Peak Regulatory T Cells (Tregs)
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.
Time frame: Baseline and Day 85
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Fold Change From Baseline in Peak Regulatory T Cells (Tregs) | 1.15 Fold change from baseline |
| MK-6194 Low Dose (Panel A) | Fold Change From Baseline in Peak Regulatory T Cells (Tregs) | 1.86 Fold change from baseline |
| MK-6194 High Dose (Panel B-E) | Fold Change From Baseline in Peak Regulatory T Cells (Tregs) | 1.69 Fold change from baseline |
| MK-6194 High Dose (Panel F) | Fold Change From Baseline in Peak Regulatory T Cells (Tregs) | 1.58 Fold change from baseline |
Secondary
Geometric Mean Accumulation Ratio of AUC of MK-6194
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.
Time frame: Day 1 (Predose and 12 hours postdose), Day 8, Day 15, Day 29 (Predose and 12 hours postdose), Day 36, and Day 43
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the BLQ or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | Geometric Mean Accumulation Ratio of AUC of MK-6194 | 0.35 Ratio |
| MK-6194 High Dose (Panel B-E) | Geometric Mean Accumulation Ratio of AUC of MK-6194 | 0.98 Ratio |
Secondary
Geometric Mean Accumulation Ratio of Cmax of MK-6194
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.
Time frame: Day 1 (Predose and 12 hours postdose), Day 8, Day 15, Day 29 (Predose and 12 hours postdose), Day 36, and Day 43
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the BLQ or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | Geometric Mean Accumulation Ratio of Cmax of MK-6194 | 0.84 Ratio |
| MK-6194 High Dose (Panel B-E) | Geometric Mean Accumulation Ratio of Cmax of MK-6194 | 0.98 Ratio |
| MK-6194 High Dose (Panel F) | Geometric Mean Accumulation Ratio of Cmax of MK-6194 | 1.35 Ratio |
Secondary
Minimum Serum Concentration (Ctrough) of MK-6194 (Day 1 to 29)
Blood samples were collected at pre-specified time points to determine the Ctrough of MK-6194 in plasma.
Time frame: Predose on Days 15 and 29
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 High Dose (Panel B-E) | Minimum Serum Concentration (Ctrough) of MK-6194 (Day 1 to 29) | 0.210 ng/mL |
Secondary
Peak Serum Concentration (Cmax) of MK-6194 (Day 1 to 29)
Blood samples were collected at pre-specified time points to determine the Cmax of MK-6194 in plasma.
Time frame: Day 1 (Predose and 12 hours postdose), Day 8, Day 15, and Day 29 (Predose and 12 hours postdose)
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the BLQ or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | Peak Serum Concentration (Cmax) of MK-6194 (Day 1 to 29) | 13.2 ng/mL |
| MK-6194 High Dose (Panel B-E) | Peak Serum Concentration (Cmax) of MK-6194 (Day 1 to 29) | 21.7 ng/mL |
| MK-6194 High Dose (Panel F) | Peak Serum Concentration (Cmax) of MK-6194 (Day 1 to 29) | 20.0 ng/mL |
Secondary
Time to Peak Serum Concentration (Tmax) of MK-6194 (Day 1 to 29)
Blood samples were collected at pre-specified time points to determine the Tmax of MK-6194 in plasma.
Time frame: Day 1 (Predose and 12 hours postdose), Day 8, Day 15, and Day 29 (Predose and 12 hours postdose)
Population: The analysis population consisted of all participants who were randomized to MK-6194 and had data available. Samples were excluded if they were at the BLQ or unevaluable. Samples received thawed were unevaluable. For the Placebo arm, zero participants analyzed indicate data were not generated and no data were available. Panels were pre-specified in the protocol to be pooled at dose group level.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6194 Low Dose (Panel A) | Time to Peak Serum Concentration (Tmax) of MK-6194 (Day 1 to 29) | 0.49 day |
| MK-6194 High Dose (Panel B-E) | Time to Peak Serum Concentration (Tmax) of MK-6194 (Day 1 to 29) | 0.49 day |
| MK-6194 High Dose (Panel F) | Time to Peak Serum Concentration (Tmax) of MK-6194 (Day 1 to 29) | 0.49 day |