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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005560-95 | EudraCT Number |
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The study was prematurely stopped due to business reasons.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Experimental | MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks. |
|
| Part 1: MK-8226 1 mg/kg | Experimental | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
|
| Part 1: MK-8226 3 mg/kg | Experimental | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
|
| Part 1: MK-8226 10 mg/kg | Experimental | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
|
| Part 1: Placebo (pooled) | Placebo Comparator | Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. |
|
| Part 2: MK-8226 3 mg/kg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8226 | Drug | MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event | 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. | Up to 32 Weeks |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | Up to 12 Weeks |
| Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2 | CCL17 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL17 are increased in allergic disease states. | Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 |
| Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Participant's Global Impression of Disease Status in Study Part 2 | Participant subjective impression of improvement of his/her disease condition is scored on a six-point scale: 0 (Clear) to 5 (Very severe disease). | Baseline, Week 4, Week 12, Week 24 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Participants were screened for study eligibility over 4 weeks prior to first dosing. Additional inclusion and exclusion criteria applied.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: MK-8226 0.3 mg/kg | MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks. |
| FG001 | Part 1: MK-8226 1 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| FG002 | Part 1: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| FG003 | Part 1: MK-8226 10 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| FG004 | Part 1: Placebo (Pooled) | Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. |
| FG005 | Part 2: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| FG006 | Part 2: Placebo | Placebo administered IV every 2 weeks for a period of 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: MK-8226 0.3 mg/kg | MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks. |
| BG001 | Part 1: MK-8226 1 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Experienced at Least One Adverse Event | 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. | The All Subjects as Treated (ASaT) population defined as all participants who received at least one dose of investigational drug was used for analysis. | Posted | Number | participants | Up to 32 Weeks |
|
Up to 32 Weeks
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: MK-8226 0.3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Erysipelas | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
|
| Part 2: Placebo | Placebo Comparator | Placebo administered IV every 2 weeks for a period of 12 weeks. |
|
| Placebo | Drug | Placebo administered IV every 2 weeks for a period of 12 weeks. |
|
| Baseline, Week 12 |
CCL22 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL22 are increased in allergic disease states. |
| Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 |
| Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | 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. | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 |
| AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 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. | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
| Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | 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. | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 |
| Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 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. | Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84 |
| Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 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. | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
| Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 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. | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
| Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2 | 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). | Baseline, Week 4, Week 8, Week 24 |
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of Clear or Almost Clear in Study Part 2 | 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). | Baseline, Week 4, Week 8, Week 12, Week 24 |
| Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2 | 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. | Baseline, Week 4, Week 12, Week 24 |
| Change From Baseline in Participant Pruritus in Study Part 2 | 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). | Baseline, Week 4, Week 12, Week 24 |
| Change From Baseline in Participant Sleep Disturbance in Study Part 2 | 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). | Baseline, Week 4, Week 12, Week 24 |
| Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2 | Oral antihistamines (i.e., diphenhydramine, acrivastine fenistil) were provided as as-needed rescue medication for severe pruritus. | Up to Week 12 |
| Percentage of Participants With >=50% Improvement in EASI Score | 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). | Baseline, Week 12, Week 24 |
| Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | 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). | Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224 |
| Protocol Violation |
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| Withdrawal by Subject |
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| Lost to Follow-up |
|
| Physician Decision |
|
| Pregnancy |
|
| Study Terminated By Sponsor |
|
| BG002 | Part 1: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| BG003 | Part 1: MK-8226 10 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| BG004 | Part 1: Placebo (Pooled) | Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. |
| BG005 | Part 2: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| BG006 | Part 2: Placebo | Placebo administered IV every 2 weeks for a period of 12 weeks. |
| BG007 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Part 1: MK-8226 0.3 mg/kg |
MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks. |
| OG001 | Part 1: MK-8226 1 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| OG002 | Part 1: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| OG003 | Part 1: MK-8226 10 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| OG004 | Part 1: Placebo (Pooled) | Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. |
| OG005 | Part 2: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. |
| OG006 | Part 2: Placebo | Placebo administered IV every 2 weeks for a period of 12 weeks. |
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | The ASaT population defined as all participants who received at least one dose of investigational drug was used for analysis. | Posted | Number | participants | Up to 12 Weeks |
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| Primary | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | 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). | The Full Analysis Set (FAS) defined as all randomized subjects who received at least one dose of study treatment with baseline and at least one post-dose assessment (EASI) was used for analysis. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 12 |
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| Secondary | Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2 | CCL17 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL17 are increased in allergic disease states. | No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from Baseline [BL] in EASI) did not demonstrate adequate effect in an interim futility analysis. The study was early terminated from a business perspective. | Posted | Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 |
|
|
| Secondary | Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2 | CCL22 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL22 are increased in allergic disease states. | 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 study was early terminated from a business perspective. | Posted | Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 |
|
|
| Secondary | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | 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. | The Per-Protocol (PP) population defined as all participants compliant with study procedure with data available (AUC0-tau) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg*hr/mL | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 |
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| Secondary | AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 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. | The PP population defined as all participants compliant with study procedure with data available (AUC0-last) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg*hr/mL | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
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| Secondary | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | 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. | The PP population defined as all participants compliant with study procedure with data available (Cmax) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 |
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| Secondary | Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 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. | The PP population defined as all participants compliant with study procedure with data available (CL) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/day/kg | Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84 |
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| Secondary | Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 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. | The PP population defined as all participants compliant with study procedure with data available (Vd) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/kg | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
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| Secondary | Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 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 PP population defined as all participants compliant with study procedure with data available (t1/2) from at least one treatment was used for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | days | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 |
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| Secondary | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2 | 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). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 8, Week 24 |
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| Secondary | Percentage of Participants With an Investigator Global Assessment (IGA) Score of Clear or Almost Clear in Study Part 2 | 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). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 8, Week 12, Week 24 |
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| Secondary | Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2 | 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. | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 12, Week 24 |
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| Secondary | Change From Baseline in Participant Pruritus in Study Part 2 | 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). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 12, Week 24 |
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| Secondary | Change From Baseline in Participant Sleep Disturbance in Study Part 2 | 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). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 12, Week 24 |
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| Secondary | Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2 | Oral antihistamines (i.e., diphenhydramine, acrivastine fenistil) were provided as as-needed rescue medication for severe pruritus. | 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 study was early terminated from a business perspective. | Posted | Up to Week 12 |
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| Other Pre-specified | Change From Baseline in the Participant's Global Impression of Disease Status in Study Part 2 | Participant subjective impression of improvement of his/her disease condition is scored on a six-point scale: 0 (Clear) to 5 (Very severe disease). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 4, Week 12, Week 24 |
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| Secondary | Percentage of Participants With >=50% Improvement in EASI Score | 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). | 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 study was early terminated from a business perspective. | Posted | Baseline, Week 12, Week 24 |
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| Secondary | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | 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). | The ADA evaluable population defined as all participants with at least one ADA sample available after treatment with MK-8226 or placebo was used for analysis. | Posted | Number | Participants | Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224 |
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|
| 0 |
| 9 |
| 8 |
| 9 |
| EG001 | Part 1: MK-8226 1 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. | 0 | 9 | 6 | 9 |
| EG002 | Part 1: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. | 0 | 8 | 6 | 8 |
| EG003 | Part 1: MK-8226 10 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. | 1 | 10 | 7 | 10 |
| EG004 | Part 1: Placebo (Pooled) | Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. | 0 | 8 | 7 | 8 |
| EG005 | Part 2: MK-8226 3 mg/kg | MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks. | 0 | 13 | 10 | 13 |
| EG006 | Part 2: Placebo | Placebo administered IV every 2 weeks for a period of 12 weeks. | 1 | 8 | 7 | 8 |
| Abortion induced | Surgical and medical procedures | MedDRA 17.1 | Systematic Assessment |
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| Blepharitis | Eye disorders | MedDRA 17.1 | Systematic Assessment |
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| Conjunctivitis allergic | Eye disorders | MedDRA 17.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Food poisoning | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Oral mucosal blistering | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Palatal swelling | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Gravitational oedema | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Bacterial infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Furuncle | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Herpes ophthalmic | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Herpes simplex | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Rash pustular | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Superinfection bacterial | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Vulvovaginal candidiasis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Heart rate irregular | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Streptococcus test positive | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Abnormal weight gain | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Carpal tunnel syndrome | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Amenorrhoea | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
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| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Alopecia areata | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Blister | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Dyshidrotic eczema | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Skin mass | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Week 10 (n=8,5,6,6) |
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| Week 10 (n=8,6,6,6) |
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| Treatment emergent ADA positive |
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| ADA positive: Max titer 1:10 |
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| ADA positive: Max titer 1:50 |
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| ADA positive: Neutralizing response positive |
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