Clinical trial NCT01679951: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Swollen and tender joints
Methotrexate
Immunology
Dose range finding study
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-09-06
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from baseline in DAS28 (CRP) at Week 24
timeFrame: Baseline and Week 24
measure: Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: DAS28 (CRP) response rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: DAS28 (ESR) response rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: DAS28 (CRP) remission rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: DAS28 (ESR) remission rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Hybrid ACR response at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Change from baseline in HAQ-DI score at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percent change from baseline in ESR levels at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percent change from baseline in ACR components at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Number of patients with adverse events
timeFrame: Up to Week 28
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Gilbert
country: United States
state: Arizona
city: Covina
country: United States
state: California
city: Palm Harbor
country: United States
state: Florida
city: Granger
country: United States
state: Indiana
city: Frederick
country: United States
state: Maryland
city: Freehold
country: United States
state: New Jersey
city: Charlotte
country: United States
state: North Carolina
city: Charleston
country: United States
state: South Carolina
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
Study officials:
affiliation: Janssen Research and Development LLC
name: Janssen Research and Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: