Study of Subcutaneous Golimumab in Chinese Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

• Sponsor: Centocor, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01248780
• Collaborator: Schering-Plough (Industry)
• Enrollment: 264
• Locations: 9
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 29.3
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of golimumab in Chinese patients with rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Golimumab; Drug: Placebo; Drug: Methotrexate (MTX)	Phase 3

Detailed Description

Golimumab is a type of tumor necrosis factor (TNF)-inhibitor. TNF is a naturally occurring substance in the body, and this substance may cause long-term inflammation. Golimumab may help fight disease by blocking the activity of TNF in the body and reducing inflammation and pain. Each patient who is allowed to join the study will be put into a group randomly, like flipping a coin. Patients may get either golimumab or placebo (which looks like the drug being studied but has no active ingredients, for example a sugar pill). The chance that the patient will get golimumab is 1 to 1, a 50% chance to receive golimumab and a 50% chance to receive placebo. If the patient does not have an improvement in their joints at the Week 16 visit compared to when they entered the study, and are in Group 1 (placebo group), the patient will receive golimumab 50 mg every 4 weeks starting at Week 16. If the patient is in Group 2 (golimumab 50 mg), the patient will continue to receive golimumab every 4 weeks starting at Week 16. If the patient is in Group 1 and is still receiving placebo injections, because there was improvement in their joints at Week 16, the patient will receive golimumab 50 mg every 4 weeks starting from Week 24. If the patient is in Group 2 (golimumab 50 mg) or is already receiving golimumab injections at week 24, the patient will continue to receive golimumab every 4 weeks. Safety will be monitored throughout the study, including drawing blood and looking at laboratory tests, vital signs (e.g., blood pressure), and the frequency and type of adverse events (side effects). The patient will be in the study approximately 56 weeks. Patients will receive placebo or active compound (golimumab 50 mg subcutaneous injections) every four weeks from randomization (Week 0) until Week 48.

Study Design

• Study Type: Interventional
• Actual Enrollment: 264 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Golimumab in the Treatment of Chinese Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Golimumab + methotrexate (MTX) Participants will receive golimumab 50 mg as subcutaneous (SC) (under the skin) injections administered every 4 weeks for up to 48 weeks. In addition, participants will receive a stable dose of MTX.	Drug: Golimumab; 50 mg subcutaneous (SC) injection every 4 weeks for up to 48 weeks; Drug: Methotrexate (MTX); A stable dose of MTX (oral or injectable) will be administered to participants according to the local prescribing guidelines for up to 48 weeks.
Experimental: Placebo + methotrexate (MTX) Participants will be administered Placebo SC injections at Weeks 0, 4, 8, 12, 16, and Week 20 followed by golimumab 50 mg SC injections at Week 24 and every 4 weeks thereafter through Week 48. In addition, participants will receive a stable dose of MTX.	Drug: Placebo; Placebo SC injections at Weeks 0, 4, 8, 12, 16, and Week 20 followed by golimumab 50 mg SC injections at Week 24 and every 4 weeks thereafter up to Week 48.; Drug: Methotrexate (MTX); A stable dose of MTX (oral or injectable) will be administered to participants according to the local prescribing guidelines for up to 48 weeks.

Outcome Measures

Primary Outcome Measures

1. American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14 [Week 14]

   ACR 20 response is defined as >= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.

Secondary Outcome Measures

1. Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein) [Week 14]

   DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A DAS28 (using CRP) responder is defined as a participant with a DAS28 response of "Good" or "Moderate" at Week 14. A "Good" response is defined as a patient with a DAS28 score of <= 3.2 at Week 14 with improvement from Baseline in DAS28 score of > 1.2. A "Moderate" response was defined as a patient with DAS28 score of >3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of >0.6 to >1.2 The table below shows the number of participants in each treatment group who were DAS28 responders at Week 14.

2. American College of Rheumatology 20 Response, Using CRP, at Week 24 [Week 24]

   ACR 20 response is defined as >= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.

3. HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline [Baseline to Week 24]

   The HAQ assesses the degree of difficulty a person has in accomplishing tasks in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). The full range of the HAQ scale is 0-24 with 0 being the best possible outcome. The HAQ score is calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3 with 0 being the best possible outcome (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, or 3=unable to do). The mean change from baseline at Week 24 in HAQ score is provided below for each treatment group. A negative change from baseline is indicative of a lesser degree of difficulty in accomplishing tasks assessed in the HAQ.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis for at least 6 months

• Be on a stable dose of methotrexate for 4 weeks

• Have at least 4 swollen and 4 tender joints

Exclusion Criteria:

• Prior exposure to biologic anti-TNFalpha agents

• Inflammatory diseases other than rheumatoid arthritis

• Treatment with Disease Modifying Anti-rheumatic drug (DMARDs)/systemic immunosuppressives other than methotrexate during the 4 weeks prior to the first administration of study agent

• History of, or ongoing, chronic or recurrent infectious disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China
2		Chengdu		China
3		Hefei		China
4		Jinan		China
5		Nanjing		China
6		Shanghai		China
7		Suzhou		China
8		Wuhan		China
9		Xi'An		China

Sponsors and Collaborators

• Centocor, Inc.
• Schering-Plough

Investigators

• Study Director: Centocor, Inc. Clinical Trial, Centocor, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT01248780
• Other Study ID Numbers: CR015913; C0524T28
• First Posted: Nov 25, 2010
• Last Update Posted: Sep 6, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Centocor, Inc.: Rheumatoid Arthritis; injection; golimumab; simponi
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Golimumab; Methotrexate

Study Results

Participant Flow

Pre-assignment Detail	In this trial, 264 participants were randomly assigned to the 2 treatment arms.

Arm/Group Title	Group I: Placebo + MTX -> Golimumab 50 mg + MTX	Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 48 if early escape; golimumab 50 mg SC injections every 4 weeks from Week 24 to Week 48 if not early escape. In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 48; In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
Period Title: Overall Study
STARTED	132	132
COMPLETED	123	117
NOT COMPLETED	9	15

Baseline Characteristics

Arm/Group Title	Group I: Placebo + MTX -> Golimumab 50 mg + MTX	Group II: Golimumab 50 mg + MTX	Total
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 48 if early escape; golimumab 50 mg SC injections every 4 weeks from Week 24 to Week 48 if not early escape. In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 48; In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Total of all reporting groups
Overall Participants	132	132	264
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (12.16)	47.7 (11.46)	47.2 (11.81)
Sex: Female, Male (Count of Participants)
Female	104 78.8%	110 83.3%	214 81.1%
Male	28 21.2%	22 16.7%	50 18.9%

Outcome Measures

1. Primary Outcome

Title	American College of Rheumatology (ACR) 20 Response, Using CRP (C-reactive Protein), at Week 14
Description	ACR 20 response is defined as >= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.

Arm/Group Title	Group I: Placebo + MTX	Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 20 if early escape; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 20; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
Measure Participants	132	132
Number [Number of participants]	21 15.9%	54 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + MTX, Group II: Golimumab 50 mg + MTX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Disease Activity Index Score (DAS 28) Response, Using CRP (C-reactive Protein)
Description	DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A DAS28 (using CRP) responder is defined as a participant with a DAS28 response of "Good" or "Moderate" at Week 14. A "Good" response is defined as a patient with a DAS28 score of <= 3.2 at Week 14 with improvement from Baseline in DAS28 score of > 1.2. A "Moderate" response was defined as a patient with DAS28 score of >3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of >0.6 to >1.2 The table below shows the number of participants in each treatment group who were DAS28 responders at Week 14.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.

Arm/Group Title	Group I: Placebo + MTX	Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 20 if early escape; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 20; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
Measure Participants	132	132
Number [Number of participants]	40 30.3%	86 65.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + MTX, Group II: Golimumab 50 mg + MTX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	American College of Rheumatology 20 Response, Using CRP, at Week 24
Description	ACR 20 response is defined as >= 20% improvement in rheumatoid arthritis (RA) symptoms and disease activity.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.

Arm/Group Title	Group I: Placebo + MTX	Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 20 if early escape; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 20; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
Measure Participants	132	132
Number [Number of participants]	21 15.9%	56 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + MTX, Group II: Golimumab 50 mg + MTX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	HAQ (Disability Index of the Health Assessment Questionnaire) Score Change From Baseline
Description	The HAQ assesses the degree of difficulty a person has in accomplishing tasks in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). The full range of the HAQ scale is 0-24 with 0 being the best possible outcome. The HAQ score is calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3 with 0 being the best possible outcome (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, or 3=unable to do). The mean change from baseline at Week 24 in HAQ score is provided below for each treatment group. A negative change from baseline is indicative of a lesser degree of difficulty in accomplishing tasks assessed in the HAQ.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants randomized (ie, intent-to-treat population) according to their assigned treatment group regardless of whether or not they received the assigned treatment.

Arm/Group Title	Group I: Placebo + MTX	Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 20 (unless early escape at Week 16); golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 20 if early escape; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).	Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 20; In addition, subjects received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
Measure Participants	132	132
Mean (Standard Deviation) [Scores on a scale]	0.1525 (0.69164)	-0.2623 (0.56767)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + MTX, Group II: Golimumab 50 mg + MTX
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Up to Week 56
Adverse Event Reporting Description	4 patients in Group I received placebo only and are not included in the safety analysis set at Week 56. 1 patient in group 2 did not receive any treatment (see participant flow) and is not included in the safety analysis set at Week 56.
Arm/Group Title	Group I: Placebo + MTX -> Golimumab 50 mg + MTX		Group II: Golimumab 50 mg + MTX
Arm/Group Description	Placebo SC injections every 4 weeks from Week 0 to Week 12 and early escaped to receive golimumab 50 mg SC injections every 4 weeks from Week 16 to Week 48; or placebo SC injections every 4 weeks from Week 0 to Week 20 and crossed over to receive golimumab 50 mg SC injections every 4 weeks from Week 24 to Week 48. In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).		Golimumab 50 mg SC injections every 4 weeks from Week 0 to Week 48; In addition, participants received a stable dose of methotrexate (MTX) capsules (>= 7.5 mg/week and <= 20 mg/week).
All Cause Mortality
	Group I: Placebo + MTX -> Golimumab 50 mg + MTX		Group II: Golimumab 50 mg + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group I: Placebo + MTX -> Golimumab 50 mg + MTX		Group II: Golimumab 50 mg + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/128 (3.1%)		8/131 (6.1%)
Blood and lymphatic system disorders
Granulocytopenia	0/128 (0%)		1/131 (0.8%)
Cardiac disorders
Acute Myocardial Infarction	0/128 (0%)		2/131 (1.5%)
Coronary Artery Disease	1/128 (0.8%)		0/131 (0%)
Infections and infestations
Lung Infection	1/128 (0.8%)		0/131 (0%)
Pneumonia	0/128 (0%)		1/131 (0.8%)
Respiratory Tract Infection	0/128 (0%)		1/131 (0.8%)
Injury, poisoning and procedural complications
Spinal Compression Fracture	0/128 (0%)		1/131 (0.8%)
Femoral Neck Fracture	0/128 (0%)		1/131 (0.8%)
Investigations
White Blood Cell Count Decreased	1/128 (0.8%)		0/131 (0%)
Nervous system disorders
Cerebral Haemorrhage	0/128 (0%)		1/131 (0.8%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	1/128 (0.8%)		0/131 (0%)
Other (Not Including Serious) Adverse Events
	Group I: Placebo + MTX -> Golimumab 50 mg + MTX		Group II: Golimumab 50 mg + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/128 (31.3%)		35/131 (26.7%)
Blood and lymphatic system disorders
Anaemia	8/128 (6.3%)		2/131 (1.5%)
Infections and infestations
Upper Respiratory Tract Infection	32/128 (25%)		25/131 (19.1%)
Investigations
Liver Function Test Abnormal	7/128 (5.5%)		8/131 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.