An Efficacy and Safety Study of JNJ-26113100 in the Treatment of Adult Atopic Dermatitis

This study has been terminated.
(The study was stopped due to a non-clinical safety finding.)
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00455429
First received: April 1, 2007
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Atopic Dermatitis
Drug: Placebo
Drug: JNJ-26113100 (50 mg) once daily
Drug: JNJ-26113100 (100 mg) once daily
Drug: JNJ-26113100 (100 mg) twice daily
Drug: JNJ-26113100 (250 mg) twice daily
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Investigator's Global Assessment (IGA) Score at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Visual Analog Scale (VAS) Score for Pruritus at Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    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 Achieving Treatment Response as "Clear" or "Almost Clear "in IGA [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 50% Reduction in EASI Score at Week 6 [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 Achieving Greater Than (>) or Equal to (=) 75% Reduction in VAS Score for Pruritus at Week 6 [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 Greater Than (>) or Equal to (=) 50% Reduction in VAS Score for Pruritus at Week 6 [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 Greater Than (>) or Equal to (=) 25% Reduction in VAS Score for Pruritus at Week 6 [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 Who Had at Least 1 Flare [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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.

  • Number of Flare Occurrences Per Participant [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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 Who Had at Least 1 Worsening AD Event [ Time Frame: Baseline up to Week 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Plasma Concentration of JNJ-26113100 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic (PK) analysis were collected before dosing and at 0.25 to 3 hours after dosing at randomization (Day 1) and Week 3 visit and at 0.25 to 3 hours, 4 to 6 hours, and 7 to 12 hours after dosing at Week 6.


Enrollment: 84
Study Start Date: April 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Matching placebo capsules to JNJ-26113100 (50 milligram [mg]) orally once daily or 100 mg orally once daily or 100 mg orally twice daily or 250 mg orally twice daily for 6 weeks.
Experimental: JNJ-26113100 (50 mg) once daily Drug: JNJ-26113100 (50 mg) once daily
JNJ-26113100 (50 mg) capsules orally once daily for 6 weeks.
Experimental: JNJ-26113100 (100 mg) once daily Drug: JNJ-26113100 (100 mg) once daily
JNJ-26113100 (100 mg) capsules orally once daily for 6 weeks.
Experimental: JNJ-26113100 (100 mg) twice daily Drug: JNJ-26113100 (100 mg) twice daily
JNJ-26113100 (100 mg) capsules orally twice daily for 6 weeks.
Experimental: JNJ-26113100 (250 mg) twice daily Drug: JNJ-26113100 (250 mg) twice daily
JNJ-26113100 (250 mg) capsules orally twice daily for 6 weeks.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:-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 Exclusion Criteria:-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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455429

Locations
United States, Alabama
Huntsville, Alabama, United States
United States, California
Los Angeles, California, United States
Sacramento, California, United States
San Diego, California, United States
Stanford, California, United States
Vista, California, United States
United States, Florida
Jacksonville, Florida, United States
United States, Illinois
Chicago, Illinois, United States
Skokie, Illinois, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
Rochester, New York, United States
Stony Brook, New York, United States
United States, Ohio
Sylvania, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
College Station, Texas, United States
San Antonio, Texas, United States
United States, Washington
Seattle, Washington, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development L.L.C Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00455429     History of Changes
Other Study ID Numbers: CR012946, C-2006-004
Study First Received: April 1, 2007
Results First Received: February 28, 2013
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Atopic Dermatitis
JNJ-26113100

Additional relevant MeSH terms:
Dermatitis, Atopic
Dermatitis
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014