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Efficacy and Safety of CDP6038 in Patients With Rheumatoid Arthritis With an Unsuccessful Response to Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Biological: CDP6038
Biological: Tocilizumab (Actemra or RoActemra)
Other: Placebo sc
Other: Placebo iv
Registration Number
NCT01242488
Lead Sponsor
UCB Pharma
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
221
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
CDP6038 60 mg sc every 2 weeks plus methotrexateCDP6038-
Placebo sc every 2 weeks plus methotrexatePlacebo iv-
CDP6038 60 mg sc every 4 weeks plus methotrexatePlacebo iv-
CDP6038 120 mg sc every 4 weeks plus methotrexatePlacebo iv-
Tocilizumab 8 mg/kg iv every 4 weeks plus methotrexateTocilizumab (Actemra or RoActemra)-
Placebo sc every 2 weeks plus methotrexatePlacebo sc-
Placebo sc every 4 weeks plus methotrexatePlacebo sc-
CDP6038 120 mg sc every 2 weeks plus methotrexateCDP6038-
CDP6038 120 mg sc every 2 weeks plus methotrexatePlacebo iv-
CDP6038 240 mg sc every 2 weeks plus methotrexatePlacebo iv-
Tocilizumab 8 mg/kg iv every 4 weeks plus methotrexatePlacebo sc-
Placebo sc every 4 weeks plus methotrexatePlacebo iv-
CDP6038 240 mg sc every 2 weeks plus methotrexateCDP6038-
CDP6038 240 mg sc every 4 weeks plus methotrexatePlacebo iv-
CDP6038 60 mg sc every 2 weeks plus methotrexatePlacebo iv-
CDP6038 60 mg sc every 4 weeks plus methotrexateCDP6038-
CDP6038 240 mg sc every 4 weeks plus methotrexatePlacebo sc-
CDP6038 60 mg sc every 4 weeks plus methotrexatePlacebo sc-
CDP6038 120 mg sc every 4 weeks plus methotrexateCDP6038-
CDP6038 120 mg sc every 4 weeks plus methotrexatePlacebo sc-
CDP6038 240 mg sc every 4 weeks plus methotrexateCDP6038-
Primary Outcome Measures
NameTimeMethod
Change from Baseline in the Disease Activity Score (C-reactive protein) [DAS28(CRP)] for CDP6038 and placeboBaseline, Week 12
Secondary Outcome Measures
NameTimeMethod
American College of Rheumatology 70% response (ACR70) rates for the CDP6038 and placebo arms.From Baseline to Week 12
American College of Rheumatology 50% response (ACR50) rates for the CDP6038 and placebo arms.From Baseline to Week 12
American College of Rheumatology 20% response (ACR20) rates for the CDP6038 and placebo arms.From Baseline to Week 12

Trial Locations

Locations (82)

132

🇺🇸

Houston, Texas, United States

181

🇺🇸

Houston, Texas, United States

158

🇺🇸

San Diego, California, United States

121

🇺🇸

Salt Lake City, Utah, United States

118

🇺🇸

Scottsdale, Arizona, United States

209

🇬🇧

Torquay, Devon, United Kingdom

152

🇺🇸

Toms River, New Jersey, United States

103

🇺🇸

Hot Springs, Arkansas, United States

400

🇧🇪

Liege, Belgium

166

🇺🇸

Mesa, Arizona, United States

201

🇬🇧

Wigan, Lancashire, United Kingdom

127

🇺🇸

Covina, California, United States

154

🇺🇸

Paradise Valley, Arizona, United States

125

🇺🇸

Jonesboro, Arkansas, United States

177

🇺🇸

Los Angeles, California, United States

184

🇺🇸

Long Beach, California, United States

149

🇺🇸

Sacramento, California, United States

104

🇺🇸

Palo Alto, California, United States

164

🇺🇸

Upland, California, United States

129

🇺🇸

Santa Maria, California, United States

101

🇺🇸

Trumbull, Connecticut, United States

137

🇺🇸

Norwalk, Connecticut, United States

141

🇺🇸

Hamden, Connecticut, United States

111

🇺🇸

Lewes, Delaware, United States

176

🇺🇸

Aventura, Florida, United States

151

🇺🇸

DeBary, Florida, United States

178

🇺🇸

Sarasota, Florida, United States

186

🇺🇸

Daytona Beach, Florida, United States

114

🇺🇸

Jupiter, Florida, United States

113

🇺🇸

Stockbridge, Georgia, United States

156

🇺🇸

Rock Island, Illinois, United States

183

🇺🇸

Pinellas Park, Florida, United States

116

🇺🇸

Idaho Falls, Idaho, United States

153

🇺🇸

Savannah, Georgia, United States

157

🇺🇸

Tampa, Florida, United States

168

🇺🇸

Springfield, Illinois, United States

102

🇺🇸

Lincoln, Nebraska, United States

133

🇺🇸

Cedar Rapids, Iowa, United States

172

🇺🇸

Kansas City, Kansas, United States

112

🇺🇸

Saint Louis, Missouri, United States

171

🇺🇸

Freehold, New Jersey, United States

134

🇺🇸

Saint Louis, Missouri, United States

185

🇺🇸

Saint Clair Shores, Michigan, United States

110

🇺🇸

Oklahoma City, Oklahoma, United States

174

🇺🇸

Brooklyn, New York, United States

163

🇺🇸

New Brunswick, New Jersey, United States

100

🇺🇸

Dayton, Ohio, United States

108

🇺🇸

Columbus, Ohio, United States

150

🇺🇸

Cincinnati, Ohio, United States

106

🇺🇸

Nashville, Tennessee, United States

117

🇺🇸

Wexford, Pennsylvania, United States

165

🇺🇸

Duncansville, Pennsylvania, United States

105

🇺🇸

Nashville, Tennessee, United States

128

🇺🇸

Dallas, Texas, United States

126

🇺🇸

Houston, Texas, United States

120

🇺🇸

Amarillo, Texas, United States

135

🇺🇸

Austin, Texas, United States

138

🇺🇸

Houston, Texas, United States

139

🇺🇸

Chesapeake, Virginia, United States

144

🇺🇸

Tomball, Texas, United States

142

🇺🇸

Victoria, Texas, United States

119

🇺🇸

Seattle, Washington, United States

175

🇺🇸

Tacoma, Washington, United States

136

🇺🇸

Beckley, West Virginia, United States

401

🇧🇪

Brussels, Belgium

206

🇬🇧

Essex, United Kingdom

205

🇬🇧

London, United Kingdom

204

🇬🇧

Newcastle Upon Tyne, United Kingdom

208

🇬🇧

Southampton, United Kingdom

140

🇺🇸

South Miami, Florida, United States

130

🇺🇸

Gainesville, Georgia, United States

143

🇺🇸

Nassau Bay, Texas, United States

148

🇺🇸

La Jolla, California, United States

107

🇺🇸

Wildomar, California, United States

162

🇺🇸

Newnan, Georgia, United States

145

🇺🇸

Mesquite, Texas, United States

160

🇺🇸

Moline, Illinois, United States

109

🇺🇸

Belmont, North Carolina, United States

115

🇺🇸

Rochester, New York, United States

170

🇺🇸

Charlotte, North Carolina, United States

122

🇺🇸

San Antonio, Texas, United States

167

🇺🇸

Clarksburg, West Virginia, United States

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