A Phase Ib Randomized, Double-Blinded, Placebo-Controlled Multiple Rising Dose Clinical Trial to Evaluate the Safety, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Intravenous MK-8226 in Patients With Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 65
- 主要终点
- Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: MK-8226 (Drug)
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.
干预措施: MK-8226 (Drug)
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.
干预措施: MK-8226 (Drug)
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.
干预措施: MK-8226 (Drug)
Part 1: Placebo (pooled)
Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks.
干预措施: Placebo (Drug)
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.
干预措施: MK-8226 (Drug)
Part 2: Placebo
Placebo administered IV every 2 weeks for a period of 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2(Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16)
- Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2(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(Days 1, 3, 5, 9, 14, 70, 72, 74, 84)
- Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration(Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84)
- Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2(Baseline, Week 4, Week 12, Week 24)
- 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)
- Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration(Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224)
- Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration(Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224)
- 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)
- Change From Baseline in Participant Pruritus in Study Part 2(Baseline, Week 4, Week 12, Week 24)
- Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration(Days 1, 3, 5, 9, 14, 70, 72, 74, 84)
- Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2(Baseline, Week 4, Week 8, Week 24)
- Change From Baseline in Participant Sleep Disturbance in Study Part 2(Baseline, Week 4, Week 12, Week 24)
- Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2(Up to Week 12)
- Percentage of Participants With >=50% Improvement in EASI Score(Baseline, Week 12, Week 24)
- Number of Participants Positive for Anti-Drug Antibody (ADA) Formation(Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224)