Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response Switching to Cimzia

• Sponsor: Michael Schiff, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01147341
• Collaborator: UCB Pharma (Industry)
• Enrollment: 37
• Locations: 12
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Purpose of the study is to determine if Cimzia is safe and effective in subjects who have received previous treatment with a TNF-alpha inhibitor other than Cimzia.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Cimzia; Drug: Placebo	Phase 4

Detailed Description

This is a Phase IV, randomized, multi-center, double-blind, parallel-group 12-week study of Cimzia with concomitant methotrexate (MTX) or other DMARD compared to MTX or other DMARD alone in patients with an inadequate secondary therapeutic response to a TNF-alpha inhibitor as defined above and active rheumatoid arthritis (RA) followed by a 12-week open-label phase with concomitant MTX or other DMARD and Cimzia.

Subjects must washout from the previous TNF inhibitor for at least 4 weeks prior to the baseline visit. Subjects unable to tolerate MTX must have been on a stable dose of another non-biologic DMARD for at least 3 months. Subjects' diagnosis of RA must be based on the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis.

Subjects will be screened for eligibility and, up to 28 days later, at the baseline visit, randomized to one of two treatment groups (2:1): Cimzia or placebo (in addition to concomitant MTX or other DMARD). All subjects will continue MTX/other DMARD at the same dose utilized prior to study entry.

After the Week 12 study visit, all subjects will have the opportunity to continue in the study on open-label Cimzia treatment (using an induction regimen for all subjects, regardless of their treatment in the blinded phase).

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response By Switching to Certolizumab Pegol (Cimzia)? A Phase IV, Randomized, Multi-Center, Double-Blind, Twelve-Week Study Followed by a 12-Week Open-Label Phase
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo Placebo (0.9% sodium chloride) given as 2 subcutaneous (sc) injections at weeks 0, 2, and 4, followed y 1 sc injection given an weeks 6, 8, and 10. At week 12 subjects entered the open label phase. Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.	Drug: Placebo; prefilled saline syringe; Other Names: 1 ml Sodium Cloride 0.9%
Active Comparator: active treatment with Cimzia 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 0, 2, and 4, followed by 1 sc injection at weeks 6, 8, and 10. At week 12 subjects entered the open label phase. Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.	Drug: Cimzia; prefilled 200mg Cimzia syringe SC q 2 weeks; Other Names: 1 ml liquid product containing 200mg of Certolizumab Pegol

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Achieving a Clinical Disease Activity Index (CDAI) Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 12 [Baseline to week 12]

   The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.

2. Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [From Baseline to 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 (VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale(VAS). HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

Secondary Outcome Measures

1. Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group at Week 12 [Baseline to Week 12]

   ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

2. Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP) [Baseline to Week 12]

   The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22

3. Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [Baseline to week 12]

   The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).

4. Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 12 [Baseline to week 12]

   The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement..

Other Outcome Measures

1. Proportion of Subjects Achieving a CDAI Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 24 [Baseline to Week 24]

   The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.

2. Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [Baseline to Week 24]

   ACR20 responders are subjects with at least 20% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

3. Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [Baseline to Week 24]

   ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

4. Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP) [Baseline to Week 24]

   The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22

5. Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group [Baseline to Week 24]

   The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).

6. Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 24 [Baseline to Week 24]

   The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of RA at least 6 months

• Have received treatment with a TNF-alpha inhibitor

• Be receiving Methotrexate (with folic acid)at a dose of at least 10mg/week or another non-biologic DMARD if Methotrexate intolerant Have at least 6 tender joint and 6 swollen joints

• Have an CRP greater than or equal to ULN

• Availability of a chest x-ray that shows no evidence of active TB or infection

Exclusion Criteria:

• Prior exposure to Cimzia

• Prior treatment with B-cell depleting therapy

• No significant response to previous TNF inhibitor

• Congestive heart failure

• Clinically abnormal laboratory tests

• History of cancer

• Active TB

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates of N. Alabama	Huntsville	Alabama	United States	35801
2	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona	United States	85381
3	Arizona Arthritis and Rhematolgy Research	Phoenix	Arizona	United States	85037
4	Sarasota Arthritis Research Center	Sarasota	Florida	United States	34239
5	Physician Research Collaboration, LLC	Lincoln	Nebraska	United States	68516
6	Westroads Medical Group	Omaha	Nebraska	United States	68114
7	Morristown Memorial Hospital	Morristown	New Jersey	United States	07960
8	Buffalo Rheumatology	Orchard Park	New York	United States	14127
9	Rheumatology Associates of Long Island	Smithtown	New York	United States	11787
10	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
11	Mountain State Clinical Research	Clarksburg	West Virginia	United States	26301
12	Rheumatology and Immunotherapy Center	Oak Creek	Wisconsin	United States	53154

Sponsors and Collaborators

• Michael Schiff, MD
• UCB Pharma

Investigators

• Study Director: Michael H Schiff, MD,

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• EULAR 2012 SAT0144
• Schiff,m

Publications

None provided.

• Responsible Party: Michael Schiff, MD, MD, Schiff, Michael, M.D.
• ClinicalTrials.gov Identifier: NCT01147341
• Other Study ID Numbers: CERT-001
• First Posted: Jun 22, 2010
• Last Update Posted: Jun 9, 2014
• Last Verified: May 1, 2014

• Keywords provided by Michael Schiff, MD, MD, Schiff, Michael, M.D.: rheumatoid arthritis; anti-TNF therapy
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	all patients recruited from US medical/Rheumatology clinics
Pre-assignment Detail	patients excluded from protocol if they did not meet entry criteria for active Rheumatoid arthritis

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Reporting group: Cimzia : prefilled 200mg Cimzia syringes. Cimzia 400mg SC at baseline, weeks 2 and 4 and Cimzia 200mg SC at weeks 6, 8, and 10 during the Double Blind Portion. Cimzia 400mg SC at weeks 12, 14, and 16 and Cimzia 200mg SC at weeks 18, 20, and 22. 27 patients entered the Double Blind Portion.	Reporting group: Placebo : prefilled saline syringe during the Double Blind Period 10 patients entered
Period Title: Double Blind Period
STARTED	27	10
COMPLETED	26	8
NOT COMPLETED	1	2
Period Title: Double Blind Period
STARTED	26	8
COMPLETED	22	8
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Active Treatment With Cimzia	Placebo	Total
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered	Total of all reporting groups
Overall Participants	27	10	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 85.2%	8 80%	31 83.8%
>=65 years	4 14.8%	2 20%	6 16.2%
Sex: Female, Male (Count of Participants)
Female	23 85.2%	8 80%	31 83.8%
Male	4 14.8%	2 20%	6 16.2%
Region of Enrollment (participants) [Number]
United States	27 100%	10 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Achieving a Clinical Disease Activity Index (CDAI) Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 12
Description	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

35 subjects were included in the efficacy assessment at week 12. Subjects in the efficacy assessment at week 12 completed at least 4 weeks of dosing

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	22 81.5%	2 20%

2. Secondary Outcome

Title	Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group at Week 12
Description	ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

35 subjects were included in the efficacy assessment at week 12. Subjects in the efficacy assessment at week 12 completed at least 4 weeks of dosing

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	5 18.5%	0 0%

3. Secondary Outcome

Title	Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)
Description	The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

35 subjects were included in the efficacy assessment at week 12. Subjects in the efficacy assessment at week 12 completed at least 4 weeks of dosing.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	6 22.2%	0 0%

4. Primary Outcome

Title	Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
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 (VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale(VAS). HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

35 subjects were included in the efficacy assessment at week 12. Subjects in the efficacy assessment at week 12 completed at least 4 weeks of dosing. 30 subjects who completed the 24 week study were included in the efficacy assessment at week 24.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	16 59.3%	0 0%

5. Secondary Outcome

Title	Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Description	The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	17 63%	0 0%

6. Secondary Outcome

Title	Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 12
Description	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement..
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	26	9
Number [participants]	17 63%	0 0%

7. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving a CDAI Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 24
Description	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	18 66.7%	6 60%

8. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Description	ACR20 responders are subjects with at least 20% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	12 44.4%	5 50%

9. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Description	ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	6 22.2%	3 30%

10. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)
Description	The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	7 25.9%	3 30%

11. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Description	The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	17 63%	6 60%

12. Other Pre-specified Outcome

Title	Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 24
Description	The Clinical Disease Activity (CDAI)is a composite score. Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22. A CDAI reduction of 6.5 represents moderate improvement.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

30 subjects were included in the efficacy assessment as week 24. Subjects completed 24 weeks dosing including a 12 week open-label phase.

Arm/Group Title	Active Treatment With Cimzia	Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered	Placebo : prefilled saline syringe 10 patients entered
Measure Participants	22	8
Number [participants]	16 59.3%	5 50%

Adverse Events

Time Frame	Adverse events (AEs) were collected from the time informed consent was signed through the whole study period of 24 weeks. In addition, serious adverse events were collected up to 4 weeks after completion/discontinuation of the study.
Adverse Event Reporting Description	As refer to the Safety Set which included all subjects who received at least 1 dose of study medication. Active treatment with Cimzia included those subjects in the double-blind portion of the protocol as well as the open label portion of the protocol.
Arm/Group Title	Active Treatment With Cimzia		Placebo
Arm/Group Description	Cimzia : prefilled 200mg Cimzia syringe SC q 2 weeks 27 patients entered		Placebo : prefilled saline syringe 10 patients entered
All Cause Mortality
	Active Treatment With Cimzia		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active Treatment With Cimzia		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/10 (0%)
Gastrointestinal disorders
gastric ulcer bleed	1/34 (2.9%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Active Treatment With Cimzia		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/34 (79.4%)		8/10 (80%)
Cardiac disorders
hypertension	1/34 (2.9%)	1	1/10 (10%)	1
coronary disease	1/34 (2.9%)	1	0/10 (0%)	0
Eye disorders
conjunctival hemorrhage	1/34 (2.9%)	1	0/10 (0%)	0
Gastrointestinal disorders
constipation	1/34 (2.9%)	1	0/10 (0%)	0
nausea	2/34 (5.9%)	2	0/10 (0%)	0
gastroesophageal reflux disease	1/34 (2.9%)	1	0/10 (0%)	0
vomiting	1/34 (2.9%)	1	1/10 (10%)	1
gastrointestinal virus	2/34 (5.9%)	2	0/10 (0%)	0
abdominal pain	1/34 (2.9%)	1	0/10 (0%)	0
General disorders
head congestion	1/34 (2.9%)	1	1/10 (10%)	1
hot face	1/34 (2.9%)	1	0/10 (0%)	0
allergies	1/34 (2.9%)	1	0/10 (0%)	0
fall	1/34 (2.9%)	1	0/10 (0%)	0
Infections and infestations
upper respiratory infections	5/27 (18.5%)	5	0/10 (0%)	0
cough	3/34 (8.8%)	3	1/10 (10%)	1
tooth abcess	1/34 (2.9%)	1	0/10 (0%)	0
cold sore	2/34 (5.9%)	2	0/10 (0%)	0
sinus infection	2/34 (5.9%)	2	0/10 (0%)	0
urinary tract infection	1/34 (2.9%)	1	0/10 (0%)	0
fever	1/34 (2.9%)	1	0/10 (0%)	0
spider bite	1/34 (2.9%)	1	0/10 (0%)	0
sore throat	1/34 (2.9%)	1	1/10 (10%)	1
bronchitis	3/34 (8.8%)	3	0/10 (0%)	0
viral cold	2/34 (5.9%)	2	0/10 (0%)	0
athletes foot	1/34 (2.9%)	1	0/10 (0%)	0
mouth sores	1/34 (2.9%)	1	0/10 (0%)	0
oral thrush	1/34 (2.9%)	1	1/10 (10%)	1
sinusitis	1/34 (2.9%)	1	0/10 (0%)	0
shingles	1/34 (2.9%)	1	0/10 (0%)	0
sinus congestion	1/34 (2.9%)	1	0/10 (0%)	0
rhinorrhea	1/34 (2.9%)	1	0/10 (0%)	0
chest congestion	1/34 (2.9%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
neck pain	1/34 (2.9%)	1	1/10 (10%)	1
increased knee pain	1/34 (2.9%)	1	0/10 (0%)	0
back strain	1/34 (2.9%)	1	0/10 (0%)	0
heel pain	1/34 (2.9%)	1	0/10 (0%)	0
shoulder sprain	1/34 (2.9%)	1	0/10 (0%)	0
muscle tenderness	1/34 (2.9%)	1	0/10 (0%)	0
hand pain	1/34 (2.9%)	1	0/10 (0%)	0
bruised tailbone	1/34 (2.9%)	1	0/10 (0%)	0
swollen elbow	1/34 (2.9%)	1	0/10 (0%)	0
rheumatoid arthritis flare	0/34 (0%)	0	1/10 (10%)	1
Nervous system disorders
headache	2/34 (5.9%)	2	0/10 (0%)	0
Psychiatric disorders
anxiety	1/34 (2.9%)	1	0/10 (0%)	0
Renal and urinary disorders
kidney stone	1/34 (2.9%)	1	0/10 (0%)	0
hematuria	1/34 (2.9%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
emphysema	1/34 (2.9%)	1	0/10 (0%)	0
Skin and subcutaneous tissue disorders
rash	4/34 (11.8%)	4	0/10 (0%)	0
third degree burn	1/34 (2.9%)	1	0/10 (0%)	0
actenic keratosis	1/34 (2.9%)	1	0/10 (0%)	0
acne	1/34 (2.9%)	1	0/10 (0%)	0
injection site reaction	1/34 (2.9%)	1	0/10 (0%)	0
contact dermatitis	1/34 (2.9%)	1	0/10 (0%)	0
bug bites	0/34 (0%)	0	1/10 (10%)	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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.