Certolizumab Pegol for the Treatment of Patients With Active Rheumatoid Arthritis (REALISTIC)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study started in July 2008 with subjects from the United States, Canada, France, Germany, Italy, the Netherlands, and Spain. The primary completion date occurred in March 2010, with study completion in March 2011.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 1648 subjects that were screened, 585 subjects had screen failures. Therefore, 1063 subjects were randomized in this study.

Reporting Groups

	Description
Certolizumab Pegol (CZP)	400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Placebo	Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.

Participant Flow for 2 periods

Period 1:   Double-Blind Period

	Certolizumab Pegol (CZP)	Placebo
STARTED	851	212
COMPLETED	771	184
NOT COMPLETED	80	28
Adverse Event	33	6
Lack of Efficacy	6	6
Lost to Follow-up	3	5
Withdrawal by Subject	10	2
Loss of efficacy	3	0
Other: Death	1	0
Other: Pregnancy	1	0
Other: Protocol Violation	2	0
Other: Inclusion/Exclusion criteria	6	2
Other: Site withdrew	2	0
Other: Screening failure	1	0
Other: subject withdrew consent	1	1
Other: Abnormal chest X-ray	2	1
Other: History of adenoid grown	1	0
Other: History of cancer	1	0
Other: Sponsor request	1	0
Other: Inappropriate randomization	1	0
Other: Detection of Hepatitis C Virus	1	0
Other: Subject moved	1	1
Other: Stopped taking DMARD	1	0
Other: Prohibited medication taken	2	2
Other: Transportation problems	0	1
Other: Investigator Decision	0	1

Period 2:   Open-Label Period

	Certolizumab Pegol (CZP)	Placebo
STARTED	771	184
COMPLETED	646	163
NOT COMPLETED	125	21
Adverse Event	29	4
Lack of Efficacy	30	8
Lost to Follow-up	28	4
Withdrawal by Subject	20	2
Loss of Efficacy	6	1
Other: Peripheral Neuropathy	0	1
Other: Lack of Compliance	1	1
Other: History of Basal Cell Carcinoma	1	0
Other: Moved	1	0
Other: Investigator Decision	1	0
Other: Loss of Staff (unblinded)	1	0
Other: Sponsor Request	3	0
Other: Cataract Surgery	1	0
Other: Administration of Golimumab	1	0
Other: Completion Accidently Performed	1	0
Other: Medical Monitor Recommendation	1	0

Reporting Groups

	Description
Certolizumab Pegol (CZP)	400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Placebo	Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Total	Total of all reporting groups

Baseline Measures

	Certolizumab Pegol (CZP)	Placebo	Total
Number of Participants   [units: participants]	851	212	1063
Age   [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	644	164	808
>=65 years	207	48	255
Age   [units: years] Mean ± Standard Deviation	55.4  ± 12.43	53.9  ± 12.66	55.1  ± 12.49
Gender   [units: participants]
Female	660	169	829
Male	191	43	234
Region of Enrollment   [units: participants]
France	14	0	14
United States	575	141	716
Canada	65	17	82
Spain	26	8	34
Netherlands	4	0	4
Germany	154	44	198
Italy	13	2	15

1.  Primary:

American College of Rheumatology 20% (ACR20) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

2.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use.   [ Time Frame: Baseline, Week 12 ]

3.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use.   [ Time Frame: Baseline, Week 12 ]

4.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use   [ Time Frame: Baseline, Week 12 ]

5.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use   [ Time Frame: Baseline, Week 12 ]

6.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years   [ Time Frame: Baseline, Week 12 ]

7.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years.   [ Time Frame: Baseline, Week 12 ]

8.  Secondary:

American College of Rheumatology 50% (ACR50) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

9.  Secondary:

American College of Rheumatology 70% (ACR70) Response at Week 12.   [ Time Frame: Baseline, Week 12 ]

10.  Secondary:

Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12   [ Time Frame: Baseline, Week 12 ]

11.  Secondary:

Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12   [ Time Frame: Baseline, Week 12 ]

12.  Secondary:

Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12   [ Time Frame: Baseline, Week 12 ]

13.  Secondary:

DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12   [ Time Frame: Week 12 ]

14.  Secondary:

SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12   [ Time Frame: Week 12 ]

15.  Secondary:

CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12   [ Time Frame: Week 12 ]

16.  Secondary:

Change From Baseline in Tender Joint Count (TJC) at Week 12   [ Time Frame: Baseline, Week 12 ]

17.  Secondary:

Change From Baseline in Swollen Joint Count (SJC) at Week 12   [ Time Frame: Baseline, Week 12 ]

18.  Secondary:

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12   [ Time Frame: Baseline, Week 12 ]

19.  Secondary:

Change From Baseline in C-reactive Protein (CRP) at Week 12   [ Time Frame: Baseline, Week 12 ]

20.  Secondary:

Change From Baseline in Patient’s Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

21.  Secondary:

Change From Baseline in Patient’s Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

22.  Secondary:

Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

23.  Secondary:

Time to Sustained American College of Rheumatology 20% (ACR20) Response   [ Time Frame: Baseline up to Week 12 ]

24.  Secondary:

European League Against Rheumatism (EULAR) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

25.  Secondary:

American College of Rheumatology 20% (ACR20) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

26.  Secondary:

American College of Rheumatology 50% (ACR50) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

27.  Secondary:

American College of Rheumatology 70% (ACR70) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

28.  Secondary:

Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28   [ Time Frame: Baseline, Week 28 ]

29.  Secondary:

Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28   [ Time Frame: Baseline, Week 28 ]

30.  Secondary:

Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28   [ Time Frame: Baseline, Week 28 ]

31.  Secondary:

DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28   [ Time Frame: Week 28 ]

32.  Secondary:

SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28   [ Time Frame: Week 28 ]

33.  Secondary:

CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28   [ Time Frame: Week 28 ]

34.  Secondary:

Change From Baseline in Tender Joint Count (TJC) at Week 28   [ Time Frame: Baseline, Week 28 ]

35.  Secondary:

Change From Baseline in Swollen Joint Count (SJC) at Week 28   [ Time Frame: Baseline, Week 28 ]

36.  Secondary:

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28   [ Time Frame: Baseline, Week 28 ]

37.  Secondary:

Change From Baseline in C-reactive Protein (CRP) at Week 28   [ Time Frame: Baseline, Week 28 ]

38.  Secondary:

Change From Baseline in Patient’s Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]

39.  Secondary:

Change From Baseline in Patient’s Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]

40.  Secondary:

Change From Baseline in Physician’s Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]