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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01242488
• Other study ID #: RA0056
• Secondary ID: 2010-020839-39
• Status: Completed
• Phase: Phase 2
• First received: November 15, 2010
• Last updated: August 26, 2014
• Start date: November 2010
• Est. completion date: June 2012

Study information

• Verified date: January 2013
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• CDP6038
60 mg subcutaneously (sc) at Weeks 0, 2, 4 6, 8, and 10
• CDP6038
120 mg sc at Weeks 0, 2, 4 6, 8, and 10
• CDP6038
240 mg sc at Weeks 0, 2, 4 6, 8, and 10
• Tocilizumab (Actemra or RoActemra)
8 mg/kg intravenously (iv) at Weeks 0, 4 and 8
• CDP6038
60 mg sc at Weeks 0, 4 and 8
• CDP6038
240 mg sc at Weeks 0, 4 and 8
• CDP6038
120 mg sc at Weeks 0, 4 and 8

Other:
• Placebo sc
0.9% Sodium chloride for injection at Weeks 0, 2, 4 6, 8, and 10
• Placebo sc
0.9% Sodium chloride for injection at Weeks 2, 6 and 10
• Placebo iv
0.9% Sodium chloride for injection at Weeks 0, 4 and 8

Locations

Country	Name	City	State
Belgium	401	Brussels
Belgium	400	Liege
United Kingdom	206	Essex
United Kingdom	205	London
United Kingdom	204	Newcastle Upon Tyne
United Kingdom	208	Southampton
United Kingdom	209	Torquay	Devon
United Kingdom	201	Wigan	Lancashire
United States	120	Amarillo	Texas
United States	135	Austin	Texas
United States	176	Aventura	Florida
United States	136	Beckley	West Virginia
United States	109	Belmont	North Carolina
United States	174	Brooklyn	New York
United States	133	Cedar Rapids	Iowa
United States	170	Charlotte	North Carolina
United States	139	Chesapeake	Virginia
United States	150	Cincinnati	Ohio
United States	167	Clarksburg	West Virginia
United States	108	Columbus	Ohio
United States	127	Covina	California
United States	128	Dallas	Texas
United States	100	Dayton	Ohio
United States	186	Daytona	Florida
United States	151	Debary	Florida
United States	165	Duncansville	Pennsylvania
United States	171	Freehold	New Jersey
United States	130	Gainesville	Georgia
United States	141	Hamden	Connecticut
United States	103	Hot Springs	Arkansas
United States	126	Houston	Texas
United States	132	Houston	Texas
United States	138	Houston	Texas
United States	181	Houston	Texas
United States	116	Idaho Falls	Idaho
United States	125	Jonesboro	Arkansas
United States	114	Jupiter	Florida
United States	172	Kansas City	Kansas
United States	148	La Jolla	California
United States	111	Lewes	Delaware
United States	102	Lincoln	Nebraska
United States	184	Long Beach	California
United States	177	Los Angeles	California
United States	166	Mesa	Arizona
United States	145	Mesquite	Texas
United States	160	Moline	Illinois
United States	105	Nashville	Tennessee
United States	106	Nashville	Tennessee
United States	143	Nassau Bay	Texas
United States	163	New Brunswick	New Jersey
United States	162	Newnan	Georgia
United States	137	Norwalk	Connecticut
United States	110	Oklahoma City	Oklahoma
United States	104	Palo Alto	California
United States	154	Paradise Valley	Arizona
United States	183	Pinellas Park	Florida
United States	115	Rochester	New York
United States	156	Rock Island	Illinois
United States	149	Sacramento	California
United States	121	Salt Lake City	Utah
United States	122	San Antonio	Texas
United States	158	San Diego	California
United States	129	Santa Maria	California
United States	178	Sarasota	Florida
United States	153	Savannah	Georgia
United States	118	Scottsdale	Arizona
United States	119	Seattle	Washington
United States	140	South Miami	Florida
United States	168	Springfield	Illinois
United States	185	St. Clair Shores	Michigan
United States	112	St. Louis	Missouri
United States	134	St. Louis	Missouri
United States	113	Stockbridge	Georgia
United States	175	Tacoma	Washington
United States	157	Tampa	Florida
United States	144	Tomball	Texas
United States	152	Toms River	New Jersey
United States	101	Trumbull	Connecticut
United States	164	Upland	California
United States	142	Victoria	Texas
United States	117	Wexford	Pennsylvania
United States	107	Wildomar	California

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Belgium,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in the Disease Activity Score (C-reactive protein) [DAS28(CRP)] for CDP6038 and placebo		Baseline, Week 12	No
Secondary	American College of Rheumatology 20% response (ACR20) rates for the CDP6038 and placebo arms.		From Baseline to Week 12	No
Secondary	American College of Rheumatology 50% response (ACR50) rates for the CDP6038 and placebo arms.		From Baseline to Week 12	No
Secondary	American College of Rheumatology 70% response (ACR70) rates for the CDP6038 and placebo arms.		From Baseline to Week 12	No