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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

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ClinicalTrials.gov Identifier: NCT01645280
Recruitment Status : Completed
First Posted : July 20, 2012
Results First Posted : December 19, 2014
Last Update Posted : May 12, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE June 6, 2012
First Posted Date  ICMJE July 20, 2012
Results First Submitted Date  ICMJE December 12, 2014
Results First Posted Date  ICMJE December 19, 2014
Last Update Posted Date May 12, 2016
Study Start Date  ICMJE August 2012
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2014)
Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 28 [ Time Frame: Week 28 ]
The ACR 20 responders are participants with at least 20 percent (%) improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) patient's assessment of arthritis pain-visual analog scale, 2) patient's global assessment of disease activity-visual analog scale, 3) physician's global assessment of disease activity-visual analog scale, 4) patient's assessment of physical function as measured by health assessment questionnaire-disability index (HAQ-Di), 5) C-reactive protein (CRP).
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2012)
ACR20 response at Week 28 [ Time Frame: Week 28 ]
ACR20 is the proportion of patients who achieve an American College of Rheumatology >= 20% response, which is a measurement of rheumatoid arthritis (RA) signs and symptoms
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2014)
  • Change From Baseline in Disease Activity Index Score 28 (DAS28; Using C-reactive Protein [CRP]) Score at Week 28 [ Time Frame: From Baseline to Week 28 ]
    The DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, CRP (mG/L) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity.
  • Percentage of Participants With American College of Rheumatology 20 (ACR 20) Response at Week 12 [ Time Frame: Week 12 ]
    The ACR 20 responders are participants with at least 20 percent (%) improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Patient's Assessment of Arthritis Pain-Visual Analog Scale, 2) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 3) Physician's Global Assessment of Disease Activity-Visual Analog Scale, 4) Patient's Assessment of Physical Function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI), 5) C-reactive Protein (CRP).
  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 28 [ Time Frame: Baseline and Week 28 ]
    The Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2012)
  • Change from baseline in DAS28 (using C-reactive protein [CRP]) [ Time Frame: Week 28 ]
    The DAS28 is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP (or erythrocyte sedimentation rate [ESR]), and Patient's Global Assessment of Disease Activity (GH).
  • ACR20 response [ Time Frame: Week 12 ]
  • Change from baseline in HAQ-DI score [ Time Frame: Week 28 ]
    The Health Assessment Questionnaire-Disability Index (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, indicating no difficulty, to 3, indicating inability to perform a task in that area.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: Placebo + methotrexate (MTX) (Group 1)
    Placebo: form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)
  • Drug: Ustekinumab + MTX (Group 2)
    Ustekinumab: type = exact number, unit = mg, number = 90, form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)
  • Drug: Ustekinumab + MTX (Group 3)
    Ustekinumab: type = exact number, unit = mg, number = 90, form = solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 12 weeks (Weeks 16 and 28) + MTX (pre-study dose)
  • Drug: CNTO 1959 + MTX (Group 4)
    CNTO 1959: type = exact number, unit = mg, number = 200, form = powder for solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28) + MTX (pre-study dose)
  • Drug: CNTO 1959 + MTX (Group 5)
    CNTO 1959: type = exact number, unit = mg, number = 50, form = powder for solution for injection, route = subcutaneous use, at Weeks 0, 4, then every 8 weeks (Weeks 12, 20, and 28)+ MTX (pre-study dose)
Study Arms  ICMJE
  • Placebo Comparator: Group 1
    Intervention: Drug: Placebo + methotrexate (MTX) (Group 1)
  • Experimental: Group 2
    Intervention: Drug: Ustekinumab + MTX (Group 2)
  • Experimental: Group 3
    Intervention: Drug: Ustekinumab + MTX (Group 3)
  • Experimental: Group 4
    Intervention: Drug: CNTO 1959 + MTX (Group 4)
  • Experimental: Group 5
    Intervention: Drug: CNTO 1959 + MTX (Group 5)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 26, 2015)
274
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2012)
250
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Bulgaria,   Chile,   Colombia,   Czech Republic,   Hungary,   Poland,   Russian Federation,   Singapore,   Ukraine,   United States
Removed Location Countries Korea, Republic of,   Mexico,   Peru,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01645280
Other Study ID Numbers  ICMJE CR100736
CNTO1275ARA2001 ( Other Identifier: Janssen Research & Development, LLC )
2011-001122-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Janssen Research & Development, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Janssen Research & Development, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP