Clinical trial NCT00718718: A Study of Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Official title: A Phase 2, 2-Part, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept, Dose-finding Study Evaluating the Efficacy and Safety of CNTO 136 Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Rheumatoid Arthritis
Active Rheumatoid Arthritis
CNTO 136
Interleukin-6
Anti-interleukin-6 monoclonal antibody
Methotrexate
Placebo
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2008-07-21
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy.

Detailed description: This is a multicenter, double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) study. This study will be conducted in 2 parts (Part A and Part B). Each part consists of 3 phases: screening (approximately 1 month prior to the start of study medication), treatment phase (Part A: 22 weeks and Part B: 24 weeks), and follow-up phase (approximately 4 months after the last administration of study medication). In Part A, participants will be randomly assigned to 2 groups to receive CNTO 136 100 mg and placebo for 22 weeks. All participants in Part A, will be crossed over at Week 12 from placebo to CNTO 136 (for Group 1) and from CNTO 136 to placebo (for Group 2). In Part B, participants will be randomly assigned to 5 groups to receive placebo and/or 1 of 3 doses of CNTO 136 (100mg, 50mg or 25mg) for 24 weeks. Participants in Part B, Group 1 will be crossed over at Week 12 from placebo to CNTO 136. All participants should be maintained on a stable dose of MTX for at least 6 weeks prior to the start of study medication through Week 24. Safety will be evaluated by the assessment of adverse events, vital signs, clinical findings, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be approximately 42 weeks.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
* Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
* MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
* Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
* C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
* Agree to use one of the contraception methods defined in the protocol

Exclusion Criteria:

* Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
* Family history of/ have long QT syndrome; or a history of second or third-degree heart block
* Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
* Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
* Positive human immunodeficiency virus test, hepatitis B or hepatitis C
* History of / have chronic or recurrent infectious disease, history of / active tuberculosis
* Have serious infection within 2 months prior to start of study medication

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 (Part B)
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in Disease Activity Index Score 28 (DAS28) Based on C-reactive Protein (CRP) at Week 12 (Part A and Part B)
timeFrame: Baseline, Week 12
measure: Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12 (Part A)
timeFrame: Week 12
measure: Serum Sirukumab Concentrations Through Week 38 (Part A)
timeFrame: Week 0, Day 2, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 10, Week 10 Day 4, Week 10 Day 7, Week 12, Week 14, Week 18, Week 22, Week 24, and Week 38
measure: Serum Sirukumab Concentrations Through Week 38 (Part B)
timeFrame: Week 0, Day 5, Day 8, Day 11, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 24 Day4, Week 24 Day7, Week 26, Week 28, Week 30, Week 34 and Week 38
measure: Percent Improvement From Baseline in Serum C-Reactive Protein (CRP) At Week 2 (Part A and Part B)
timeFrame: Baseline, Week 2
Other outcomes:
Locations:
city: Aventura
country: United States
state: Florida
city: Lexington
country: United States
state: Kentucky
city: Frederick
country: United States
state: Maryland
city: Kalamazoo
country: United States
state: Michigan
city: Charlotte
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: Anderson
country: United States
state: South Carolina
city: Budapest
country: Hungary
city: Győr
country: Hungary
city: Kecskemét
country: Hungary
city: Goshogawara
country: Japan
city: Hitachi
country: Japan
city: Kawagoe
country: Japan
city: Kitakyushu
country: Japan
city: Miyazaki
country: Japan
city: Sasebo
country: Japan
city: Shinjuku-Ku
country: Japan
city: Tomigusuku
country: Japan
city: Busan
country: Korea, Republic of
city: Dae-Gu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Ciudad De Mexico
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: Bialystok
country: Poland
city: Bydgoszcz N/A
country: Poland
city: Elblag
country: Poland
city: Gdynia
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St Petersburg
country: Russian Federation
Study officials:
affiliation: Centocor, Inc.
name: Centocor Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.