Clinical trial NCT01645280: A Study of the Effectiveness and Safety of Ustekinumab (STELARA) and CNTO 1959 Administered Under the Skin of Patients With Active Rheumatoid Arthritis, Despite Existing Methotrexate Therapy
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Study Evaluating the Efficacy and Safety of Ustekinumab (STELARA®) and CNTO 1959 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: Active rheumatoid arthritis
Ustekinumab
STELARA
CNTO 1959
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 274
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 study is to evaluate the efficacy of ustekinumab and CNTO 1959 in reducing the signs and symptoms of disease in patients with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy and to evaluate the safety of ustekinumab and CNTO 1959 in this population.

Detailed description: This is a randomized (patients assigned to treatment by chance), double-blind (study personnel and patients will not know what treatment is being assigned to patients), multicenter, placebo-controlled (a placebo is a treatment identical in appearance to the study agent, but containing no active ingredient), dose-ranging study. Approximately 250 patients will be randomly assigned to 1 of 5 treatment groups. The maximum length of study participation is 54 weeks, including a 6-week screening period. The end of the study will be the last follow-up visit of the last patient. Study visits and evaluations will occur, and patient safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Have had RA for at least 6 months prior to screening
* Have a diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association - Be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening
* Have been treated with and tolerated MTX for at least 6 months prior to screening, and have a MTX dose of \>= 10 mg and \<= 25 mg per week and stable for at least 12 weeks prior to first administration of study agent
* Have active RA, defined as persistent disease activity with both of the following criteria: at least 6 swollen and 6 tender joints at the time of screening and baseline; serum C-reactive protein (CRP) \>= 0.80 mg/dL at screening. The investigator may consider the patient eligible if the CRP value is at least 0.80 mg/dL in a single repeat testing during the screening period
* If using oral corticosteroids, must be on a stable dose of \<= 10 mg/day of prednisone or an equipotent dose of another oral corticosteroid for at least 2 weeks prior to the first administration of study agent. If not using corticosteroids at Week 0, the patient must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
* If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics regularly for RA, the patient must have been on a stable dose for at least 2 weeks prior to the first administration of study agent. If not using NSAIDs or other analgesics for RA at Week 0, the patient must have not received NSAIDs or other analgesics for RA for at least 2 weeks prior to the first administration of study agent

Exclusion Criteria:

* Has other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease, that might confound the evaluation of the benefit of study agent therapy
* Has current signs or symptoms of liver insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled
* Has any known malignancy or history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to the first administration of study agent)
* Has a history of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location, or clinically significant splenomegaly
* Has known allergies, hypersensitivity, or intolerance to ustekinumab or CNTO 1959 or its inactive ingredients
* Has ever received any approved or investigational biologic agent

Primary outcomes:
measure: Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 28
timeFrame: Week 28
Secondary outcomes:
measure: Change From Baseline in Disease Activity Index Score 28 (DAS28; Using C-reactive Protein [CRP]) Score at Week 28
timeFrame: From Baseline to Week 28
measure: Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 12
timeFrame: Week 12
measure: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 28
timeFrame: Baseline and Week 28
Other outcomes:
Locations:
city: Palm Harbor
country: United States
state: Florida
city: Rock Island
country: United States
state: Illinois
city: Saint Louis
country: United States
state: Missouri
city: Buenos Aires
country: Argentina
city: Ciudad Autónoma De Buenos Aires
country: Argentina
city: San Juan
country: Argentina
city: Tucumán
country: Argentina
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Osorno
country: Chile
city: Bogota
country: Colombia
city: Bucaramanga
country: Colombia
city: Cali
country: Colombia
city: Chia
country: Colombia
city: Medellin
country: Colombia
city: Medellín
country: Colombia
city: Hlucin
country: Czech Republic
city: Kladno
country: Czech Republic
city: Uherske Hradiste
country: Czech Republic
city: Budapest
country: Hungary
city: Gödöllő
country: Hungary
city: Szekesfehervar
country: Hungary
city: Szombathely
country: Hungary
city: Veszprém
country: Hungary
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Sopot
country: Poland
city: Sosnowiec
country: Poland
city: Warszawa
country: Poland
city: Warszaw
country: Poland
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: St.-Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Singapore
country: Singapore
city: Donetsk
country: Ukraine
city: Ivano-Frankovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Simferopol
country: Ukraine
city: Ternopil
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Smolen JS, Agarwal SK, Ilivanova E, Xu XL, Miao Y, Zhuang Y, Nnane I, Radziszewski W, Greenspan A, Beutler A, Baker D. A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis. 2017 May;76(5):831-839. doi: 10.1136/annrheumdis-2016-209831. Epub 2017 Jan 13.