Trial Outcomes & Findings for A Study of Intravenous MK-8226 in Participants With Moderate-to-Severe Atopic Dermatitis (MK-8226-003) (NCT NCT01732510)

Participants were screened for study eligibility over 4 weeks prior to first dosing. Additional inclusion and exclusion criteria applied.

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

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Reduction from baseline in EASI at Week 12 (interim analysis data). The EASI assesses intensity of four lesion characteristics (erythema, infiltration/population, excoriation, lichenification) each rated on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities). Affected areas in each region are assessed as percentage of body surface (head \[10%\], trunk \[30%\], upper extremities \[20%\], and lower extremities \[40%\]). The total score is a sum of each region score and can range from 0 (absent disease) to 72 (severe disease).

CCL17 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL17 are increased in allergic disease states.

CCL22 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL22 are increased in allergic disease states.

AUC(0-tau) defined as AUC from time zero to tau where tau is the dosing interval (312 hours) was determined for the first and last periods of MK-8226 dosing. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 70 (incl. predose), 72, 74, 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

AUC0-last defined as AUC up to the last measured concentration was determined for the last period of dosing (starting Week 10 \[Day 70\]) up to the last measurement. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

Cmax was determined for the first and last periods of MK-8226 dosing. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 70 (incl. predose), 72, 74, and 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

CL, the volume of plasma cleared of drug per unit time, was determined for the last period of dosing (starting Week 10 \[Day 70\]) in the treatment period. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 28 (incl. predose), 42 (incl. predose), 56 (incl. predose), 70 (incl. predose), 72, 74, and 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

Vd, a theoretical approximation of degree to which the drug distributes in body tissue rather than plasma (higher Vd indicates greater tissue distribution), was determined for the last period of dosing (starting Week 10 \[Day 70\]) in the treatment period. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

t1/2, the time needed for the concentration of drug to reach half the initial concentration, was determined for the last period of dosing (starting Week 10 \[Day 70\]) up to the last measurement. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

The EASI assesses intensity of four lesion characteristics (erythema, infiltration/population, excoriation, lichenification) each rated on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities). Affected areas in each region are assessed as percentage of body surface (head \[10%\], trunk \[30%\], upper extremities \[20%\], and lower extremities \[40%\]). The total score is a sum of each region score and can range from 0 (absent disease) to 72 (severe disease).

Percentage of participants achieving an IGA of atopic dermatitis of "clear-0" or "almost clear-1". The IGA is a six-point scale measuring the severity of disease at time of physical examination of the participant by the physician. The IGA is scored 0 (Clear) to 5 (Very severe disease).

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities) along with 2) subjective symptoms of pruritus and sleep disturbance as reported by the patient on a visual analog scale (VAS) from 1 to 10 cm (increasing severity). Physician assessment of affected areas in each region is made as percentage of body surface (head \[10%\], trunk \[30%\], upper extremities \[20%\], and lower extremities \[40%\]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x \[sum of intensity score for each of the 6 items\]) + participant's subjective score.

Skin pruritus (itching) is a typical characteristic of atopic dermatitis. Participant subjective assessment of pruritus (component of SCORAD) is rated on a VAS ranging from 1 to 10 cm (increasing severity).

Sleep disturbance (sleep loss, disruption, or interference) due to unremitting pruritus and other causes is a quality of life issue in moderate to severe atopic dermatitis. Participant subjective assessment of sleep disturbance (component of SCORAD) over the past 3 days is rated on a VAS ranging from 1 to 10 cm (increasing severity).

Oral antihistamines (i.e., diphenhydramine, acrivastine fenistil) were provided as as-needed rescue medication for severe pruritus.

The EASI assesses intensity of four lesion characteristics (erythema, infiltration/population, excoriation, lichenification) each rated on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities). Affected areas in each region are assessed as percentage of body surface (head \[10%\], trunk \[30%\], upper extremities \[20%\], and lower extremities \[40%\]). The total score is a sum of each region score and can range from 0 (absent disease) to 72 (severe disease).

Testing for ADA positivity and neutralizing response and antibody titre quantification are performed with blood (serum) samples collected at baseline (Day 1 predose) and Days 14, 28, 42, 56, 74, 112, and 224. Neutralizing response refers to ADA neutralizing interference with study drug assessed in vitro. Non-Treatment emergent ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with study drug (i.e., at predose).

Participant subjective impression of improvement of his/her disease condition is scored on a six-point scale: 0 (Clear) to 5 (Very severe disease).