Atopic Dermatitis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGMK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.
DRUGPlacebo
Placebo administered IV every 2 weeks for a period of 12 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight \>=40 kg * Clinical diagnosis of atopic dermatitis for at least 6 months prior * Candidate for systemic or phototherapy (i.e., failed topical treatment) * Moderate-to-severe disease as defined by Body Surface Area (BSA) ≥10%, EASI ≥12, and IGA ≥3 * No clinically significant abnormality on electrocardiogram * No history of active or latent tuberculosis (TB) and no signs or symptoms suggestive of TB * No history of active or latent TB and no signs or symptoms suggestive of TB * History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors within 3 months before the screening visit
Exclusion criteria
* Concurrent significant skin disease * Any significant organ dysfunction within 6 months prior * History of clinically significant heart disease * History of neoplastic disease * Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) * Infection requiring oral antibiotics within 2 weeks prior * Receipt of a live virus vaccine within 4 weeks prior * Inability to refrain from topical or systemic therapy during course of the study * Had major surgery or donated or lost \>=1 unit of blood within 4 weeks prior * Participation in another study within 4 weeks prior * Current or regular user of illicit drugs or a history of drug or alcohol abuse within 1 year prior * Pregnant, breast-feeding, or anticipated to conceive during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | Baseline, Week 12 | 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). |
| Number of Participants Who Experienced at Least One Adverse Event | Up to 32 Weeks | 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. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 12 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 | 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. |
| AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 | 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. |
| Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Days 1, 3, 5, 9, 14, 70, 72, 74, 84 | 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. |
| Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84 | 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. |
| Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 | 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. |
| Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224 | 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. |
| Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2 | Baseline, Week 4, Week 8, Week 24 | 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). |
| Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2 | Baseline, Week 4, Week 12, Week 24 | 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. |
| Change From Baseline in Participant Pruritus in Study Part 2 | Baseline, Week 4, Week 12, Week 24 | 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). |
| Change From Baseline in Participant Sleep Disturbance in Study Part 2 | Baseline, Week 4, Week 12, Week 24 | 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). |
| Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2 | Up to Week 12 | Oral antihistamines (i.e., diphenhydramine, acrivastine fenistil) were provided as as-needed rescue medication for severe pruritus. |
| Percentage of Participants With >=50% Improvement in EASI Score | Baseline, Week 12, Week 24 | 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). |
| Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224 | 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). |
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of Clear or Almost Clear in Study Part 2 | Baseline, Week 4, Week 8, Week 12, Week 24 | 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). |
| Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2 | Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 | CCL17 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL17 are increased in allergic disease states. |
| Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2 | Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16 | CCL22 is a pro-allergic chemokine that is assessed in human plasma. Levels of CCL22 are increased in allergic disease states. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Participant's Global Impression of Disease Status in Study Part 2 | Baseline, Week 4, Week 12, Week 24 | Participant subjective impression of improvement of his/her disease condition is scored on a six-point scale: 0 (Clear) to 5 (Very severe disease). |
Participant flow
Pre-assignment details
Participants were screened for study eligibility over 4 weeks prior to first dosing. Additional inclusion and exclusion criteria applied.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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. | 9 |
| 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. | 8 |
| 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. | 10 |
| Part 1: Placebo (Pooled) Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks. | 8 |
| 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. | 13 |
| Part 2: Placebo Placebo administered IV every 2 weeks for a period of 12 weeks. | 8 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study Terminated By Sponsor | 0 | 0 | 0 | 1 | 0 | 12 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 2 | 1 | 5 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: MK-8226 1 mg/kg | Part 1: MK-8226 3 mg/kg | Part 1: MK-8226 10 mg/kg | Part 1: Placebo (Pooled) | Part 2: MK-8226 3 mg/kg | Part 2: Placebo | Part 1: MK-8226 0.3 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 10 Participants | 8 Participants | 13 Participants | 8 Participants | 8 Participants | 64 Participants |
| Age, Continuous | 30.8 years STANDARD_DEVIATION 13.4 | 41.6 years STANDARD_DEVIATION 12.6 | 34.7 years STANDARD_DEVIATION 10.2 | 37.8 years STANDARD_DEVIATION 14.2 | 38.3 years STANDARD_DEVIATION 11.5 | 33.9 years STANDARD_DEVIATION 12.9 | 49.0 years STANDARD_DEVIATION 11.8 | 38.0 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants | 5 Participants | 8 Participants | 3 Participants | 4 Participants | 32 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 5 Participants | 33 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 6 / 9 | 6 / 8 | 7 / 10 | 7 / 8 | 10 / 13 | 7 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 8 | 1 / 10 | 0 / 8 | 0 / 13 | 1 / 8 |
Outcome results
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).
Time frame: Baseline, Week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | -5.77 Score on a scale | Standard Deviation 6.17 |
| Part 1: MK-8226 1 mg/kg | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | -8.40 Score on a scale | Standard Deviation 9.39 |
| Part 1: MK-8226 3 mg/kg | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | -10.20 Score on a scale | Standard Deviation 7.23 |
| Part 1: MK-8226 10 mg/kg | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | -7.78 Score on a scale | Standard Deviation 8.35 |
| Part 1: Placebo (Pooled) | Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 | -0.38 Score on a scale | Standard Deviation 6.37 |
Comparison: The reduction from baseline in EASI at week 12 for participants receiving MK-8226 3 mg/kg was compared to placebo (MK-8226 3 mg - Placebo). The constrained longitudinal data analysis model used variance component covariance matrix to model correlation among repeated visits, without adjustment for interaction of treatment group by visit.p-value: 0.01595% CI: [-16.87, -2.77]Constrained longitudinal data analysis
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.
Time frame: Up to 12 Weeks
Population: The ASaT population defined as all participants who received at least one dose of investigational drug was used for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| Part 1: Placebo (Pooled) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 participants |
| Part 2: Placebo | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 participants |
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.
Time frame: Up to 32 Weeks
Population: The All Subjects as Treated (ASaT) population defined as all participants who received at least one dose of investigational drug was used for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Who Experienced at Least One Adverse Event | 8 participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Who Experienced at Least One Adverse Event | 6 participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Who Experienced at Least One Adverse Event | 6 participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Who Experienced at Least One Adverse Event | 7 participants |
| Part 1: Placebo (Pooled) | Number of Participants Who Experienced at Least One Adverse Event | 7 participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Who Experienced at Least One Adverse Event | 10 participants |
| Part 2: Placebo | Number of Participants Who Experienced at Least One Adverse Event | 7 participants |
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.
Time frame: Days 1, 3, 5, 9, 14, 70, 72, 74, 84
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 1 (n=9,7,8,10) | 1000 μg*hr/mL | Geometric Coefficient of Variation 18.2 |
| Part 1: MK-8226 0.3 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 10 (n=8,5,6,6) | 2310 μg*hr/mL | Geometric Coefficient of Variation 11 |
| Part 1: MK-8226 1 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 10 (n=8,5,6,6) | 8530 μg*hr/mL | Geometric Coefficient of Variation 15.4 |
| Part 1: MK-8226 1 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 1 (n=9,7,8,10) | 3300 μg*hr/mL | Geometric Coefficient of Variation 29.3 |
| Part 1: MK-8226 3 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 1 (n=9,7,8,10) | 9300 μg*hr/mL | Geometric Coefficient of Variation 19.1 |
| Part 1: MK-8226 3 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 10 (n=8,5,6,6) | 21100 μg*hr/mL | Geometric Coefficient of Variation 28.8 |
| Part 1: MK-8226 10 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 1 (n=9,7,8,10) | 31400 μg*hr/mL | Geometric Coefficient of Variation 11.2 |
| Part 1: MK-8226 10 mg/kg | Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration | Week 10 (n=8,5,6,6) | 82100 μg*hr/mL | Geometric Coefficient of Variation 16.2 |
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.
Time frame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 6460 μg*hr/mL | Geometric Coefficient of Variation 34.3 |
| Part 1: MK-8226 1 mg/kg | AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 22600 μg*hr/mL | Geometric Coefficient of Variation 65.8 |
| Part 1: MK-8226 3 mg/kg | AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 47100 μg*hr/mL | Geometric Coefficient of Variation 97.2 |
| Part 1: MK-8226 10 mg/kg | AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration | 264000 μg*hr/mL | Geometric Coefficient of Variation 25.2 |
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).
Time frame: Baseline, Week 4, Week 12, Week 24
Population: 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.
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).
Time frame: Baseline, Week 4, Week 12, Week 24
Population: 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.
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).
Time frame: Baseline, Week 4, Week 8, Week 24
Population: 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.
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.
Time frame: Baseline, Week 4, Week 12, Week 24
Population: 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.
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.
Time frame: Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84
Population: The PP population defined as all participants compliant with study procedure with data available (CL) from at least one treatment was used for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 3.04 mL/day/kg | Geometric Coefficient of Variation 11 |
| Part 1: MK-8226 1 mg/kg | Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 2.81 mL/day/kg | Geometric Coefficient of Variation 15.4 |
| Part 1: MK-8226 3 mg/kg | Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 3.33 mL/day/kg | Geometric Coefficient of Variation 28.8 |
| Part 1: MK-8226 10 mg/kg | Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration | 2.9 mL/day/kg | Geometric Coefficient of Variation 16.2 |
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.
Time frame: Days 1, 3, 5, 9, 14, 70, 72, 74, 84
Population: The PP population defined as all participants compliant with study procedure with data available (Cmax) from at least one treatment was used for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 10 (n=8,6,6,6) | 11.7 μg/mL | Geometric Coefficient of Variation 9.63 |
| Part 1: MK-8226 0.3 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 1 (n=9,8,8,10) | 7.12 μg/mL | Geometric Coefficient of Variation 21.9 |
| Part 1: MK-8226 1 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 1 (n=9,8,8,10) | 21.6 μg/mL | Geometric Coefficient of Variation 26 |
| Part 1: MK-8226 1 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 10 (n=8,6,6,6) | 42.4 μg/mL | Geometric Coefficient of Variation 20.1 |
| Part 1: MK-8226 3 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 10 (n=8,6,6,6) | 106 μg/mL | Geometric Coefficient of Variation 19.6 |
| Part 1: MK-8226 3 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 1 (n=9,8,8,10) | 60.3 μg/mL | Geometric Coefficient of Variation 18 |
| Part 1: MK-8226 10 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 10 (n=8,6,6,6) | 398 μg/mL | Geometric Coefficient of Variation 17.1 |
| Part 1: MK-8226 10 mg/kg | Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration | Week 1 (n=9,8,8,10) | 200 μg/mL | Geometric Coefficient of Variation 12.1 |
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).
Time frame: Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 0 Participants |
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
| Part 1: MK-8226 0.3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 0 Participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 1 Participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 0 Participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 0 Participants |
| Part 1: MK-8226 1 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 1 Participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 1 Participants |
| Part 1: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 1 Participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 0 Participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 0 Participants |
| Part 1: MK-8226 10 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 0 Participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 1 Participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 1 Participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 2 Participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 0 Participants |
| Part 2: MK-8226 3 mg/kg | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
| Part 2: Placebo | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Neutralizing response positive | 0 Participants |
| Part 2: Placebo | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:50 | 0 Participants |
| Part 2: Placebo | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Non Treatment emergent ADA positive | 0 Participants |
| Part 2: Placebo | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | Treatment emergent ADA positive | 0 Participants |
| Part 2: Placebo | Number of Participants Positive for Anti-Drug Antibody (ADA) Formation | ADA positive: Max titer 1:10 | 0 Participants |
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.
Time frame: Up to Week 12
Population: 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.
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).
Time frame: Baseline, Week 12, Week 24
Population: 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.
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).
Time frame: Baseline, Week 4, Week 8, Week 12, Week 24
Population: 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.
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.
Time frame: Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16
Population: 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.
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.
Time frame: Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16
Population: 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.
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.
Time frame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 23.6 days | Geometric Coefficient of Variation 33.5 |
| Part 1: MK-8226 1 mg/kg | Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 30 days | Geometric Coefficient of Variation 15.9 |
| Part 1: MK-8226 3 mg/kg | Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 24.7 days | Geometric Coefficient of Variation 51.3 |
| Part 1: MK-8226 10 mg/kg | Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration | 28.7 days | Geometric Coefficient of Variation 15.7 |
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.
Time frame: Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224
Population: The PP population defined as all participants compliant with study procedure with data available (Vd) from at least one treatment was used for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: MK-8226 0.3 mg/kg | Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 103 mL/kg | Geometric Coefficient of Variation 27.6 |
| Part 1: MK-8226 1 mg/kg | Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 122 mL/kg | Geometric Coefficient of Variation 26.8 |
| Part 1: MK-8226 3 mg/kg | Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 102 mL/kg | Geometric Coefficient of Variation 62.1 |
| Part 1: MK-8226 10 mg/kg | Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration | 120 mL/kg | Geometric Coefficient of Variation 25.3 |
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).
Time frame: Baseline, Week 4, Week 12, Week 24
Population: 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.