A Double-Blind, Randomized, Placebo-Controlled, Sequential Cohort Exploratory Study of the Safety and Efficacy of JNJ-26113100 in the Treatment of Adult Atopic Dermatitis That is Moderate in Severity
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 84
- 主要终点
- Change From Baseline in Visual Analog Scale (VAS) Score for Pruritus at Week 6
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of four dose regimens (pattern of giving treatment) of JNJ-26113100 in the treatment of adult Atopic Dermatitis ([AD]; skin rash, inflammation) that is moderate in severity.
详细描述
This study is a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study drug assigned by chance), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), sequential cohort exploratory study to evaluate the safety and effectiveness of JNJ-26113100 in the treatment of adult AD that is moderate in severity, including its effect on inflammatory biomarkers (biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease). Participants will be sequentially assigned to 50 milligram (mg) once daily, 100 mg once daily, 100 mg twice daily or 250 mg twice daily cohort and randomly assigned to receive JNJ-26113100 or matching placebo.
The total duration of the study will be approximately 8 weeks. Participants will be asked to follow-up at the end of Week 1, 2, 3, 4, 5 and 6. A study termination visit (Day 57) will be conducted at the end of Week 8. Skin biopsies from atopic dermatitis lesions will be collected during the study to assess changes in the inflammatory disease state. Participants developing flares of their disease may be treated with triamcinolone acetonide 0.1 percent ointment twice daily for up to 7 days. Efficacy will be assessed using Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI) and Visual Analog Scale (VAS). Blood and urine samples will be collected for standard safety laboratory tests, to measure the level of drug and effect of the drug on inflammatory biomarkers. Participant's safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants with Atopic Dermatitis (skin rash, inflammation) involving greater than or equal to 10 percent body surface area
- •Female participants must have a negative serum pregnancy test at screening
- •With the exception of well-controlled asthma, allergic rhinitis and food allergies, participants must be in good general health prior to study participation with no clinically significant abnormalities as assessed by the investigator and determined by medical history, physical examination, blood chemistry, complete blood count, coagulation tests, urinalysis and electrocardiogram (ECG)
- •Male subjects must consent to utilize a medically acceptable method of contraception throughout the study including the washout period and for three months after the study is completed
- •Female participants of child bearing potential must consent to utilize a medically acceptable method of contraception throughout the study including the washout period and for three months after the study is completed
排除标准
- •Evidence of clinically significant hepatic, reproductive, gastrointestinal, renal, hematologic, pulmonary, neurologic, respiratory (with the exception of well-controlled asthma), endocrine or cardiovascular abnormalities or psychiatric disorders
- •Participants with screening alanine aminotransferase, alkaline phosphatase or direct bilirubin levels above the upper limit of normal
- •Evidence of any skin condition that in the opinion of the investigator would interfere with assessment of atopic dermatitis
- •Use of any investigational drugs within the previous 30 days prior to dosing or within a period of less than five times the drug's half-life, whichever is longer
- •Use of any biologic within a period of 5 times its half-life
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
JNJ-26113100 (50 mg) once daily
干预措施: JNJ-26113100 (50 mg) once daily (Drug)
JNJ-26113100 (100 mg) once daily
干预措施: JNJ-26113100 (100 mg) once daily (Drug)
JNJ-26113100 (100 mg) twice daily
干预措施: JNJ-26113100 (100 mg) twice daily (Drug)
JNJ-26113100 (250 mg) twice daily
干预措施: JNJ-26113100 (250 mg) twice daily (Drug)
结局指标
主要结局
Change From Baseline in Visual Analog Scale (VAS) Score for Pruritus at Week 6
时间窗: Baseline and Week 6
VAS consists of 10 centimeter (cm) horizontal line and the words; 0 cm="No itch" on the left side of the line and the words 10 cm="Worst possible itch" on the right side of the line. Participants will be instructed to rate the severity of their pruritus within the previous 24 hours by drawing a vertical line across the 10 cm line at the point between "No itch" and "Worst possible itch" which best describes their itching during the preceding 24 hours.
Percentage of Participants Who Had at Least 1 Flare
时间窗: Baseline up to Week 6
Percentage of participants who had at Least 1 Flare while on treatment was assessed. A flare was considered to be present if the following criteria were met: 1) IGA was greater than or equal to 2, if IGA on most recent previous assessment was 0; 2) IGA had increased by at least 1 point, if IGA on most recent previous assessment was 1 or more.
Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 6
时间窗: Baseline and Week 6
EASI measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (greater than \[\>\] 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score.
Percentage of Participants Achieving Greater Than (>) or Equal to (=) 25% Reduction in VAS Score for Pruritus at Week 6
时间窗: Baseline up to Week 6
VAS consists of 10 centimeter (cm) horizontal line and the words; 0 cm="No itch" on the left side of the line and the words 10 cm="Worst possible itch" on the right side of the line. Participants will be instructed to rate the severity of their pruritus within the previous 24 hours by drawing a vertical line across the 10 cm line at the point between "No itch" and "Worst possible itch" which best describes their itching during the preceding 24 hours. Success is defined as an improvement of \>=75% from the baseline VAS assessment of pruritus. An improvement of \<75% is a failure.
Investigator's Global Assessment (IGA) Score at Week 6
时间窗: Week 6
Participants were reported for IGA. IGA is an overall assessment of Atopic Dermatitis (AD). IGA utilizes a 6-point scale (ranging from 0 to 5): 0=clear (noinflammatory signs of AD), 1=almost clear (just perceptible erythema, and just perceptible papulation/infiltration), 2=mild disease (mild erythema, and mild papulation/infiltration), 3=moderate disease (moderate erythema, and moderate papulation/infiltration), 4=severe disease (severe erythema, and severe papulation/infiltration) and 5=very severe disease (severe erythema, and severe papulation/infiltration with oozing/crusting).
Percentage of Participants Achieving Greater Than (>) or Equal to (=) 50% Reduction in VAS Score for Pruritus at Week 6
时间窗: Baseline up to Week 6
VAS consists of 10 centimeter (cm) horizontal line and the words; 0 cm="No itch" on the left side of the line and the words 10 cm="Worst possible itch" on the right side of the line. Participants will be instructed to rate the severity of their pruritus within the previous 24 hours by drawing a vertical line across the 10 cm line at the point between "No itch" and "Worst possible itch" which best describes their itching during the preceding 24 hours. Success is defined as an improvement of \>=75% from the baseline VAS assessment of pruritus. An improvement of \<75% is a failure.
Number of Flare Occurrences Per Participant
时间窗: Baseline up to Week 6
A flare was considered to be present if the following criteria were met: 1) IGA was greater than or equal to 2, if IGA on most recent previous assessment was 0 or 2) IGA had increased by at least 1 point, if IGA on most recent previous assessment was 1 or more.
Percentage of Participants Achieving Treatment Response as "Clear" or "Almost Clear "in IGA
时间窗: Baseline up to Week 6
Percentage of participants achieving treatment response (decrease) in IGA were assessed. IGA is used to assess AD through a 6-point scale (Range=0-5) where, 0=clear (no inflammatory signs of AD), 1=almost clear (just perceptible erythema \& perceptible papulation/infiltration), 2=mild (mild erythema \& papulation/infiltration), 3=moderate (moderate erythema \& papulation/infiltration), 4=severe (severe erythema \& papulation/infiltration) \& 5=very severe (severe erythema \& papulation/infiltration with oozing/crusting). Success is reduction of IGA to 0 or 1. Failure is reduction of IGA to \>=2.
Percentage of Participants Achieving Greater Than (>) or Equal to (=) 75% Reduction in VAS Score for Pruritus at Week 6
时间窗: Baseline up to Week 6
VAS consists of 10 centimeter (cm) horizontal line and the words; 0 cm="No itch" on the left side of the line and the words 10 cm="Worst Possible Itch" on the right side of the line. Participants will be instructed to rate the severity of their pruritus within the previous 24 hours by drawing a vertical line across the 10 cm line at the point between "No itch" and "Worst possible itch" which best describes their itching during the preceding 24 hours. Success is defined as an improvement of \>=75% from the baseline VAS assessment of pruritus. An improvement of \<75% is a failure.
Percentage of Participants Achieving 50% Reduction in EASI Score at Week 6
时间窗: Baseline up to Week 6
EASI measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (greater than \[\>\] 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. Success is defined as an improvement of \>=50% from the baseline EASI score. An improvement of \<50% is considered a failure.
Percentage of Participants Achieving Greater Than (>) or Equal to (=) 25% Reduction in EASI Score at Week 6
时间窗: Baseline up to Week 6
EASI measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (greater than \[\>\] 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. Success is defined as an improvement of \>=25% from the baseline EASI score. An improvement of \<25% is considered a failure.
Percentage of Participants Who Had at Least 1 Worsening AD Event
时间窗: Baseline up to Week 6
Percentage of Participants who had at least 1 Worsening AD Event That did not Meet Flare Criteria were assessed. Worsening of AD that did not meet flare criteria was documented. Flare was considered to be present if either of the following criteria were met: 1) IGA was=2, if IGA on most recent previous assessment was 0; 2) IGA had increased by at least 1 point, if IGA on most recent previous assessment was 1 or more.
次要结局
- Plasma Concentration of JNJ-26113100(Before dosing on Day 1, Week 3, Week 6; after dosing at 0.25 to 3 hours on Day 1, Week 3, Week 6; after dosing at 4 to 6 hours and 7 to 12 hours on Week 6)