Efficacy Confirmation Trial of CDP870 Without Coadministration of Methotrexate (MTX) in Japanese Rheumatoid Arthritis (RA)

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00791921
• Collaborator: UCB Japan Co. Ltd. (Industry)
• Enrollment: 230
• Locations: 7
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 32.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The objectives of this study are to verify the superiority in efficacy (American College of Rheumatology 20%: ACR20) and investigate the pharmacokinetics and safety of CDP870 versus placebo without coadministration of MTX in active RA patients in whom MTX cannot be administrated.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: CDP870; Drug: Placebo of CDP870	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Trial to Assess the Efficacy, Pharmacokinetics, and Safety of CDP870 Without Coadministration of MTX in Japanese Active RA Patients in Whom MTX Cannot be Administrated.
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CDP870 200mg 400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks	Drug: CDP870; 400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks until Week22 subcutaneously(SC)
Placebo Comparator: Placebo Placebo of CDP870	Drug: Placebo of CDP870; Placebo given every 2 weeks until Week22 (SC)

Outcome Measures

Primary Outcome Measures

1. American College of Rheumatology 20% (ACR20) Response at Week 12 [Baseline, Week 12]

   ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)

Secondary Outcome Measures

1. American College of Rheumatology 20% (ACR20) Response at Week 24 [Baseline, Week 24]

   ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have a diagnosis of adult-onset RA of at least 6 months but not longer than 15 years in duration as defined by the 1987 American College of Rheumatology classification criteria.

• Subjects must have active RA disease as defined by:

• At least 6 tender joints and 6 swollen joints

• ESR of 28 mm/hour or CRP of 2.0 mg/dL

• Subjects who have failed to respond or have been resistant to at least one DMARD (including MTX)

• Subjects in whom MTX cannot be administered for any of the reasons(incomplete response/safety concerns)

Exclusion Criteria:

• Patients who have a diagnosis of any other inflammatory arthritis

• Patients who have a secondary, non-inflammatory type of arthritis (eg, osteoarthritis, fibromyalgia)

• Patients who currently have, or who have a history of, a demyelinating or convulsive disease of the central nervous system (eg, multiple sclerosis, epilepsy)

• Patients who have NYHA (New York Heart Association) Class III or IV congestive heart failure

• Patients who currently have, or who have a history of, tuberculosis

• Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease)

• Patients who currently have, or who have a history of, malignancy

• Female patients who are breastfeeding or pregnant, who are of childbearing potential

• Patients who previously received treatment with 2 or more anti-TNFα drugs or who previously failed to respond to treatment with 1 or more aint-TNFα drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chube Region		Japan
2		Chugoku Region		Japan
3		Hokkaido Region		Japan
4		Kanto Region		Japan
5		Kinki Region		Japan
6		Kyushuh Region		Japan
7		Shikoku Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.
• UCB Japan Co. Ltd.

Investigators

• Study Chair: Katsuhisa Saito, OPCJ

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00791921
• Other Study ID Numbers: CDP870-275-08-003
• First Posted: Nov 17, 2008
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: Rheumatoid Arthritis; Certolizumab Pegol; Cimzia
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	Subjects were recruited in Japan between 2008 and 2010.
Pre-assignment Detail	Participant flow results are based on the safety set.

Arm/Group Title	CDP870 200mg	Placebo
Arm/Group Description	400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks	Placebo of CDP870
Period Title: Overall Study
STARTED	116	114
COMPLETED	82	18
NOT COMPLETED	34	96

Baseline Characteristics

Arm/Group Title	CDP870 200mg	Placebo	Total
Arm/Group Description	400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks	Placebo of CDP870	Total of all reporting groups
Overall Participants	116	114	230
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	88 75.9%	94 82.5%	182 79.1%
>=65 years	28 24.1%	20 17.5%	48 20.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.0 (10.2)	55.4 (9.8)	55.7 (10.0)
Sex: Female, Male (Count of Participants)
Female	83 71.6%	88 77.2%	171 74.3%
Male	33 28.4%	26 22.8%	59 25.7%
Region of Enrollment (participants) [Number]
Japan	116 100%	114 100%	230 100%

Outcome Measures

1. Primary Outcome

Title	American College of Rheumatology 20% (ACR20) Response at Week 12
Description	ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All 230 subjects (116 CDP 200 mg, 114 Placebo) included in the Full Analysis Set (FAS) are included in this analysis

Arm/Group Title	CDP870 200mg	Placebo
Arm/Group Description	400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks	Placebo of CDP870
Measure Participants	116	114
Number [percentage of participants]	67.2 57.9%	14.9 13.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CDP870 200mg, Placebo
	Comments	For ACR20 responder rate at Week 12, comparison between the CDP870 200 mg group and the placebo group was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Logistic
	Comments

2. Secondary Outcome

Title	American College of Rheumatology 20% (ACR20) Response at Week 24
Description	ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All 230 subjects (116 CDP 200 mg, 114 Placebo) included in the Full Analysis Set (FAS) are included in this analysis

Arm/Group Title	CDP870 200mg	Placebo
Arm/Group Description	400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks	Placebo of CDP870
Measure Participants	116	114
Number [percentage of participants]	63.8 55%	11.4 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CDP870 200mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Logistic
	Comments

Adverse Events

Time Frame	24-week double blind phase, from Baseline to Week 24
Adverse Event Reporting Description	Of the 230 subjects in the Full Analysis Set (FAS), 230 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.
Arm/Group Title	CDP870 200mg		Placebo
Arm/Group Description	400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks		Placebo of CDP870
All Cause Mortality
	CDP870 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CDP870 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/116 (11.2%)		3/114 (2.6%)
Blood and lymphatic system disorders
Leukopenia	0/116 (0%)	0	1/114 (0.9%)	1
Thrombocytopenia	1/116 (0.9%)	1	0/114 (0%)	0
Gastrointestinal disorders
Ileitis	1/116 (0.9%)	1	0/114 (0%)	0
Pancreatitis acute	1/116 (0.9%)	1	0/114 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	1/116 (0.9%)	1	0/114 (0%)	0
Infections and infestations
Cellulitis	0/116 (0%)	0	1/114 (0.9%)	1
Herpes zoster	1/116 (0.9%)	1	0/114 (0%)	0
Influenza	0/116 (0%)	0	1/114 (0.9%)	1
Pneumonia pneumococcal	1/116 (0.9%)	1	0/114 (0%)	0
Arthritis bacterial	1/116 (0.9%)	1	0/114 (0%)	0
Pneumocystis jiroveci pneumonia	1/116 (0.9%)	1	0/114 (0%)	0
Injury, poisoning and procedural complications
Spinal compression fracture	2/116 (1.7%)	2	0/114 (0%)	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	1/116 (0.9%)	1	0/114 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	0/116 (0%)	0	1/114 (0.9%)	1
Renal and urinary disorders
Calculus ureteric	1/116 (0.9%)	1	0/114 (0%)	0
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	1/116 (0.9%)	1	0/114 (0%)	0
Surgical and medical procedures
Abortion induced	0/116 (0%)	0	1/114 (0.9%)	1
Vascular disorders
Aortic dissection rupture	1/116 (0.9%)	1	0/114 (0%)	0
Other (Not Including Serious) Adverse Events
	CDP870 200mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/116 (39.7%)		41/114 (36%)
Gastrointestinal disorders
Constipation	4/116 (3.4%)	4	0/114 (0%)	0
Hepatobiliary disorders
Hepatic function abnormal	4/116 (3.4%)	5	4/114 (3.5%)	4
Infections and infestations
Nasopharyngitis	20/116 (17.2%)	23	16/114 (14%)	21
Pharyngitis	6/116 (5.2%)	6	5/114 (4.4%)	5
Upper respiratory tract infection	3/116 (2.6%)	4	4/114 (3.5%)	4
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	4/116 (3.4%)	4	14/114 (12.3%)	14
Skin and subcutaneous tissue disorders
Eczema	6/116 (5.2%)	6	3/114 (2.6%)	3
Rash	10/116 (8.6%)	11	0/114 (0%)	0
Vascular disorders
Hypertension	4/116 (3.4%)	4	1/114 (0.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.