Back to resultsA Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
JNJ-38518168 (3 mg)
JNJ-38518168 (10 mg)
JNJ-38518168 (30 mg)
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Swollen and tender joints, Methotrexate, Immunology, Dose range finding study
Eligibility Criteria
Inclusion Criteria:
- Has had rheumatoid arthritis for at least 6 months prior to the date of signing the informed consent at screening
- Must be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening
- Must have active rheumatoid arthritis (at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline and Serum C reactive protein greater than or equal to 0.80 mg/dL at the time of screening
- Has been treated with and tolerated methotrexate treatment at dosages from 10 to 25 mg/week inclusive, for a minimum of 6 months with stable dose for at least 8 weeks prior to the date of signing the informed consent at screening
Exclusion Criteria:
- Has inflammatory diseases other than rheumatoid arthritis, including but not limited to adult onset Still's disease, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and Lyme disease that might confound the evaluation of the benefit of study agent therapy
- Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive or uncontrolled
- Has ever received any approved or investigational biologic agent for a rheumatoid indication
- Has been treated with any nonbiologic disease modifying antirheumatic drugs within 4 weeks prior to the first administration of study agent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
JNJ-38518168 (3 mg/d)
JNJ-38518168 (10 mg/d)
JNJ-38518168 (30 mg/d)
Arm Description
Outcomes
Primary Outcome Measures
Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.
Secondary Outcome Measures
Change from baseline in DAS28 (CRP) at Week 24
Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24
DAS28 (CRP) response rates at Week 12 and Week 24
DAS28 (ESR) response rates at Week 12 and Week 24
DAS28 (CRP) remission rates at Week 12 and Week 24
DAS28 (ESR) remission rates at Week 12 and Week 24
American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24
An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
Hybrid ACR response at Week 12 and Week 24
The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).
ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24
According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:
when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.
Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24
The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C-reactive protein (CRP in mg/dL).
Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24
The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA, and MDGA.
Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24
The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).
Change from baseline in HAQ-DI score at Week 12 and Week 24
Percent change from baseline in ESR levels at Week 12 and Week 24
Percent change from baseline in ACR components at Week 12 and Week 24
Number of patients with adverse events
Full Information
NCT ID
NCT01679951
First Posted
September 3, 2012
Last Updated
March 13, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01679951
Brief Title
A Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate
Official Title
A Phase 2b Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Dose Range Finding Study of JNJ-38518168 in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
The decision was made to prematurely discontinue this trial due to lack of efficacy.
Study Start Date
October 31, 2012 (Actual)
Primary Completion Date
April 17, 2014 (Actual)
Study Completion Date
July 3, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this dose range finding study is to assess the effectiveness, safety and tolerability of JNJ-38518168 at doses of 3, 10, and 30 mg/d compared with placebo in patients with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy.
Detailed Description
This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), multicenter, placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), dose range finding study of JNJ-38518168 in patients with active RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week placebo-controlled period and a 4-week follow-up period between the last dose and the last visit. The duration of participation in the study for an individual patient will be up to 34 weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a 1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA will be performed at study visits. Safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Swollen and tender joints, Methotrexate, Immunology, Dose range finding study
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
272 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
JNJ-38518168 (3 mg/d)
Arm Type
Experimental
Arm Title
JNJ-38518168 (10 mg/d)
Arm Type
Experimental
Arm Title
JNJ-38518168 (30 mg/d)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=tablet, route=oral. Placebo will be administered once daily from week 0 to week 24.
Intervention Type
Drug
Intervention Name(s)
JNJ-38518168 (3 mg)
Intervention Description
Type=exact number, unit=mg, number=3, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
Intervention Type
Drug
Intervention Name(s)
JNJ-38518168 (10 mg)
Intervention Description
Type=exact number, unit=mg, number=10, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
Intervention Type
Drug
Intervention Name(s)
JNJ-38518168 (30 mg)
Intervention Description
Type=exact number, unit=mg, number=30, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Participants must have been treated with and tolerated Methotrexate (MTX) treatment at dosages from 10 to 25 milligram per week (mg/week) inclusive, for a minimum of 6 months prior to the date of signing the informed consent at screening and must have a stable MTX dose for a minimum of 8 weeks prior to the date of signing the informed consent at screening and continue to receive the same MTX dose at Week 0 through Week 24.
Primary Outcome Measure Information:
Title
Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
Description
The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Change from baseline in DAS28 (CRP) at Week 24
Time Frame
Baseline and Week 24
Title
Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24
Time Frame
Baseline, Week 12 and Week 24
Title
DAS28 (CRP) response rates at Week 12 and Week 24
Time Frame
Week 12 and Week 24
Title
DAS28 (ESR) response rates at Week 12 and Week 24
Time Frame
Week 12 and Week 24
Title
DAS28 (CRP) remission rates at Week 12 and Week 24
Time Frame
Week 12 and Week 24
Title
DAS28 (ESR) remission rates at Week 12 and Week 24
Time Frame
Week 12 and Week 24
Title
American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24
Description
An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
Time Frame
Week 12 and Week 24
Title
Hybrid ACR response at Week 12 and Week 24
Description
The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).
Time Frame
Week 12 and Week 24
Title
ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24
Description
According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:
when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.
Time Frame
Week 12 and Week 24
Title
Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24
Description
The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C-reactive protein (CRP in mg/dL).
Time Frame
Baseline, Week 12 and Week 24
Title
Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24
Description
The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA, and MDGA.
Time Frame
Baseline, Week 12 and Week 24
Title
Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24
Description
The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).
Time Frame
Week 12 and Week 24
Title
Change from baseline in HAQ-DI score at Week 12 and Week 24
Time Frame
Baseline, Week 12 and Week 24
Title
Percent change from baseline in ESR levels at Week 12 and Week 24
Time Frame
Baseline, Week 12 and Week 24
Title
Percent change from baseline in ACR components at Week 12 and Week 24
Time Frame
Baseline, Week 12 and Week 24
Title
Number of patients with adverse events
Time Frame
Up to Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has had rheumatoid arthritis for at least 6 months prior to the date of signing the informed consent at screening
Must be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening
Must have active rheumatoid arthritis (at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline and Serum C reactive protein greater than or equal to 0.80 mg/dL at the time of screening
Has been treated with and tolerated methotrexate treatment at dosages from 10 to 25 mg/week inclusive, for a minimum of 6 months with stable dose for at least 8 weeks prior to the date of signing the informed consent at screening
Exclusion Criteria:
Has inflammatory diseases other than rheumatoid arthritis, including but not limited to adult onset Still's disease, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and Lyme disease that might confound the evaluation of the benefit of study agent therapy
Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive or uncontrolled
Has ever received any approved or investigational biologic agent for a rheumatoid indication
Has been treated with any nonbiologic disease modifying antirheumatic drugs within 4 weeks prior to the first administration of study agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research and Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research and Development LLC
Official's Role
Study Director
Facility Information:
City
Huntsville
State/Province
Alabama
Country
United States
City
Gilbert
State/Province
Arizona
Country
United States
City
Covina
State/Province
California
Country
United States
City
Palm Harbor
State/Province
Florida
Country
United States
City
Granger
State/Province
Indiana
Country
United States
City
Frederick
State/Province
Maryland
Country
United States
City
Freehold
State/Province
New Jersey
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Buenos Aires
Country
Argentina
City
San Miguel De Tucuman
Country
Argentina
City
Osorno X Region
Country
Chile
City
Santiago - Macul
Country
Chile
City
Santiago
Country
Chile
City
Viña Del Mar
Country
Chile
City
Barranquilla
Country
Colombia
City
Bogota
Country
Colombia
City
Bucaramanga
Country
Colombia
City
Cali
Country
Colombia
City
Medellin
Country
Colombia
City
Medellín
Country
Colombia
City
Hlucin
Country
Czechia
City
Ostrava
Country
Czechia
City
Praha
Country
Czechia
City
Slany
Country
Czechia
City
Zlin
Country
Czechia
City
Balatonfured
Country
Hungary
City
Budapest
Country
Hungary
City
Debrecen
Country
Hungary
City
Gyulai
Country
Hungary
City
Veszprem
Country
Hungary
City
Chiba
Country
Japan
City
Fukuoka
Country
Japan
City
Hokkaido
Country
Japan
City
Kanagawa
Country
Japan
City
Kato
Country
Japan
City
Kawagoe
Country
Japan
City
Kumamoto
Country
Japan
City
Kyoto
Country
Japan
City
Matsuyama
Country
Japan
City
Osaka
Country
Japan
City
Sapporo
Country
Japan
City
Takasaki
Country
Japan
City
Tokyo
Country
Japan
City
Daegu
Country
Korea, Republic of
City
Pucheon
Country
Korea, Republic of
City
Suwon
Country
Korea, Republic of
City
Adazi
Country
Latvia
City
Riga
Country
Latvia
City
Valmiera
Country
Latvia
City
Ciudad De Mexico
Country
Mexico
City
Del Gustavo A Madero
Country
Mexico
City
Delegación Cuauhtémoc
Country
Mexico
City
Guadalajara, Jalisco
Country
Mexico
City
Guadalajara
Country
Mexico
City
Guadalaja
Country
Mexico
City
Leon
Country
Mexico
City
México
Country
Mexico
City
San Luis Potosi
Country
Mexico
City
Bialystok
Country
Poland
City
Białystok
Country
Poland
City
Katowice
Country
Poland
City
Nadarzyn
Country
Poland
City
Poznan
Country
Poland
City
Sroda Wielkopolska
Country
Poland
City
Warszawa
Country
Poland
City
Wroclaw
Country
Poland
City
Bacau
Country
Romania
City
Braila
Country
Romania
City
Bucuresti
Country
Romania
City
Sibiu
Country
Romania
City
Kazan
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
Petrozavodsk
Country
Russian Federation
City
Saint-Petersburg
Country
Russian Federation
City
Saratov
Country
Russian Federation
City
Tver
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Kaohsiung
Country
Taiwan
City
Taichung
Country
Taiwan
City
Taipei
Country
Taiwan
City
Bangkok
Country
Thailand
City
Chiang Mai
Country
Thailand
City
Donetsk
Country
Ukraine
City
Kyiv
Country
Ukraine
City
Vinnytsya
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
A Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate
We'll reach out to this number within 24 hrs