Clinical trial NCT01242488: Efficacy and Safety of CDP6038 in Patients With Rheumatoid Arthritis With an Unsuccessful Response to Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
Official title: Randomized, Double-blind, Placebo-controlled, Dose Ranging Study With an Active Comparator to Evaluate the Efficacy and Safety of CDP6038 Administered Subcutaneously for 12 Weeks to Subjects With Rheumatoid Arthritis Having Previously Failed TNF-blocker Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
CDP6038
Interleukin-6
Tocilizumab
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2010-11-17
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of CDP6038 treatment in adult subjects with active rheumatoid arthritis who have had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapy.

Detailed description: CDP6038 is a protein (antibody) that blocks interleukin-6 (IL-6), a substance involved in the inflammation associated with rheumatoid arthritis. This is a multicenter, 12-week, randomized, double-blind, placebo- and active- controlled study comparing several doses and dosage regimens (every 2 weeks and every 4 weeks) of CDP6038 to placebo and tocilizumab in patients with active rheumatoid arthritis who have had an unsuccessful response to methotrexate and previous anti-TNF therapy. The study will test if CDP6038 is more efficacious than placebo in reducing the signs and symptoms of rheumatoid arthritis at 12 weeks while maintaining an adequate safety profile. In order to maintain the study blinding all subjects will be given a subcutaneous (sc) injection (under the skin) every 2 weeks, as well as an intravenous (iv) infusion every 4 weeks. In addition subjects must remain on stable weekly doses of methotrexate. Assessments during the study include evaluations of joint pain and swelling, laboratory blood and urine tests, physical examinations, vital signs, electrocardiograms, and questionnaires. Subjects who complete the 12-week study will be eligible to enroll in a long-term extension study receiving CDP6038.

Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of rheumatoid arthritis (according to the 1987 ACR classification criteria OR a score of ≥6 as defined by the ACR/European League Against Rheumatism Classification and Diagnostic Criteria for rheumatoid arthritis ) for at least 6 months prior to screening
* Must have been treated with MTX 12.5-25 mg/week, for at least 6 weeks prior to screening. Doses of 10 to \< 12.5mg/week are allowed if there is documented intolerance
* Have moderately to severely active rheumatoid arthritis disease with at least 6 tender and 6 swollen joints
* CRP ≥1.2 times the upper limit of normal (central laboratory) or erythrocyte sedimentation rate of more than 28mm/hour
* Intolerant or inadequate response to treatment (ie, TNF blocker failure)≥1 licensed TNF-blocker therapies within 2 years of screening

Exclusion Criteria:

* Have a diagnosis of any other inflammatory arthritis or secondary, noninflammatory type of arthritis, such as psoriatic arthritis, lupus, gout, or ankylosing spondylitis
* Wheelchair bound or bedridden.
* Disease modifying antirheumatic drugs (DMARDs) other than MTX.
* Treatment with tocilizumab or any other anti-IL-6 investigational therapies at any time.
* Treatment with other biologics within 4-24 weeks (depending on the biologic)
* History of ongoing, chronic or recurrent infections or recent serious or life-threatening infection
* Known concurrent acute or chronic viral hepatitis B or C infection or human immunodeficiency virus (HIV) infection.
* Vaccinations (other than injectable influenza or pneumococcal) within 8 weeks prior to screening or plan to receive vaccines during the study
* Concurrent or history of malignancy with the exception of nonmelanoma skin cancer successfully treated more than 2 years prior to screening or cervical cancer successfully treated more than 5 years prior to screening.
* History of chronic alcohol abuse or drug addiction within the last 1 year or current drug addiction or use of illicit drugs.

Primary outcomes:
measure: Change from Baseline in the Disease Activity Score (C-reactive protein) [DAS28(CRP)] for CDP6038 and placebo
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: American College of Rheumatology 20% response (ACR20) rates for the CDP6038 and placebo arms.
timeFrame: From Baseline to Week 12
measure: American College of Rheumatology 50% response (ACR50) rates for the CDP6038 and placebo arms.
timeFrame: From Baseline to Week 12
measure: American College of Rheumatology 70% response (ACR70) rates for the CDP6038 and placebo arms.
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Mesa
country: United States
facility: 166
state: Arizona
city: Paradise Valley
country: United States
facility: 154
state: Arizona
city: Scottsdale
country: United States
facility: 118
state: Arizona
city: Hot Springs
country: United States
facility: 103
state: Arkansas
city: Jonesboro
country: United States
facility: 125
state: Arkansas
city: Covina
country: United States
facility: 127
state: California
city: La Jolla
country: United States
facility: 148
state: California
city: Long Beach
country: United States
facility: 184
state: California
city: Los Angeles
country: United States
facility: 177
state: California
city: Palo Alto
country: United States
facility: 104
state: California
city: Sacramento
country: United States
facility: 149
state: California
city: San Diego
country: United States
facility: 158
state: California
city: Santa Maria
country: United States
facility: 129
state: California
city: Upland
country: United States
facility: 164
state: California
city: Wildomar
country: United States
facility: 107
state: California
city: Hamden
country: United States
facility: 141
state: Connecticut
city: Norwalk
country: United States
facility: 137
state: Connecticut
city: Trumbull
country: United States
facility: 101
state: Connecticut
city: Lewes
country: United States
facility: 111
state: Delaware
city: Aventura
country: United States
facility: 176
state: Florida
city: Daytona Beach
country: United States
facility: 186
state: Florida
city: DeBary
country: United States
facility: 151
state: Florida
city: Jupiter
country: United States
facility: 114
state: Florida
city: Pinellas Park
country: United States
facility: 183
state: Florida
city: Sarasota
country: United States
facility: 178
state: Florida
city: South Miami
country: United States
facility: 140
state: Florida
city: Tampa
country: United States
facility: 157
state: Florida
city: Gainesville
country: United States
facility: 130
state: Georgia
city: Newnan
country: United States
facility: 162
state: Georgia
city: Savannah
country: United States
facility: 153
state: Georgia
city: Stockbridge
country: United States
facility: 113
state: Georgia
city: Idaho Falls
country: United States
facility: 116
state: Idaho
city: Moline
country: United States
facility: 160
state: Illinois
city: Rock Island
country: United States
facility: 156
state: Illinois
city: Springfield
country: United States
facility: 168
state: Illinois
city: Cedar Rapids
country: United States
facility: 133
state: Iowa
city: Kansas City
country: United States
facility: 172
state: Kansas
city: Saint Clair Shores
country: United States
facility: 185
state: Michigan
city: Saint Louis
country: United States
facility: 112
state: Missouri
city: Saint Louis
country: United States
facility: 134
state: Missouri
city: Lincoln
country: United States
facility: 102
state: Nebraska
city: Freehold
country: United States
facility: 171
state: New Jersey
city: New Brunswick
country: United States
facility: 163
state: New Jersey
city: Toms River
country: United States
facility: 152
state: New Jersey
city: Brooklyn
country: United States
facility: 174
state: New York
city: Rochester
country: United States
facility: 115
state: New York
city: Belmont
country: United States
facility: 109
state: North Carolina
city: Charlotte
country: United States
facility: 170
state: North Carolina
city: Cincinnati
country: United States
facility: 150
state: Ohio
city: Columbus
country: United States
facility: 108
state: Ohio
city: Dayton
country: United States
facility: 100
state: Ohio
city: Oklahoma City
country: United States
facility: 110
state: Oklahoma
city: Duncansville
country: United States
facility: 165
state: Pennsylvania
city: Wexford
country: United States
facility: 117
state: Pennsylvania
city: Nashville
country: United States
facility: 105
state: Tennessee
city: Nashville
country: United States
facility: 106
state: Tennessee
city: Amarillo
country: United States
facility: 120
state: Texas
city: Austin
country: United States
facility: 135
state: Texas
city: Dallas
country: United States
facility: 128
state: Texas
city: Houston
country: United States
facility: 126
state: Texas
city: Houston
country: United States
facility: 132
state: Texas
city: Houston
country: United States
facility: 138
state: Texas
city: Houston
country: United States
facility: 181
state: Texas
city: Mesquite
country: United States
facility: 145
state: Texas
city: Nassau Bay
country: United States
facility: 143
state: Texas
city: San Antonio
country: United States
facility: 122
state: Texas
city: Tomball
country: United States
facility: 144
state: Texas
city: Victoria
country: United States
facility: 142
state: Texas
city: Salt Lake City
country: United States
facility: 121
state: Utah
city: Chesapeake
country: United States
facility: 139
state: Virginia
city: Seattle
country: United States
facility: 119
state: Washington
city: Tacoma
country: United States
facility: 175
state: Washington
city: Beckley
country: United States
facility: 136
state: West Virginia
city: Clarksburg
country: United States
facility: 167
state: West Virginia
city: Brussels
country: Belgium
facility: 401
city: Liege
country: Belgium
facility: 400
city: Torquay
country: United Kingdom
facility: 209
state: Devon
city: Wigan
country: United Kingdom
facility: 201
state: Lancashire
city: Essex
country: United Kingdom
facility: 206
city: London
country: United Kingdom
facility: 205
city: Newcastle Upon Tyne
country: United Kingdom
facility: 204
city: Southampton
country: United Kingdom
facility: 208
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C, Durez P, Kretsos K. Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014 Sep;73(9):1607-15. doi: 10.1136/annrheumdis-2013-204760. Epub 2014 Mar 18.