Follow-up of Rheumatoid Arthritis (RA) Moderate to Low Disease Activity Study (CERTAIN 2)

• ClinicalTrials.gov Identifier: NCT00843778
• Recruitment Status: Completed
• First Posted: February 13, 2009
• Results First Posted: October 31, 2013
• Last Update Posted: January 30, 2014
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

Study Description

Brief Summary:

To continue to assess the clinical safety and efficacy of Certolizumab Pegol as add-on therapy with stable-dose Disease Modifying Anti-Rheumatic Drugs (DMARDs)

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Biological: Certolizumab Pegol	Phase 3

Detailed Description:

This is a Phase IIIB, multi-centre, open-label, follow-up study to study C87076 [NCT00674362] designed to continue to assess the safety and efficacy of Certolizumab Pegol.

Two different population will enter the study from C87076 [NCT00674362] and will be treated with Certolizumab Pegol every two weeks until it is commercially available for the indication of Rheumatoid Arthritis (RA) in the subject's country or region or until further notice from UCB:

Population 1: Are those subjects who failed to achieve remission at Week 20 and/or Week 24 and who completed the Week 24 assessment of study C86076 [NCT00674362].The Week 24 assessment (visit 14) of C87076 [NCT00674362] will also be the entry assessment (visit 1) for C87080. The subjects will receive Certolizumab Pegol 200 mg every two weeks. No induction period will be applied to ensure the blinding of study C87076 [NCT00674362].

Population 2: Are those subjects who achieved remission at both Week 20 and Week 24, flared up between Week 24 and Week 52 and completed the Week 52 assessment in study C87076 [NCT00674362]. The Week 52 assessment (visit 26) of C87076 [NCT00674362] will also be the entry assessment (visit 1) for C87080.

Subjects who flared prior to Week 48 in the C87076 [NCT00674362] study will receive Certolizumab Pegol 200 mg every two weeks in the C87080 study.

Those who flared at Week 48 or Week 52, will receive respectively once 400 mg Certolizumab Pegol or three times 400 mg Certolizumab Pegol at two weeks interval as part of an induction phase in the C87080 study. Thereafter the subject enters the C87080 study and will be further treated with 200 mg Certolizumab Pegol every two weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 131 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIIB, Multi-center, Open Label Follow-up Study to Evaluate the Safety and Efficacy of Certolizumab Pegol Administered Concomitantly With DMARDs in Patients With Active Rheumatoid Arthritis Who Participated in C87076.
• Study Start Date: January 2009
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: Certolizumab Pegol; Certolizumab Pegol 200 mg every two weeks at the hospital by a nurse. Certolizumab Pegol 200 mg every two weeks at the patient's home done by patient (self-injection).

Biological: Certolizumab Pegol; 200 mg every two weeks Certolizuimab Pegol 200 mg every two weeks Subjects who flared at Week 48 or Week 52 of feeder study C87076 [NCT00674362], will receive respectively once 400 mg Certolizumab Pegol or three times 400 mg Certolizumab Pegol at two weeks interval as part of an induction phase in the C87080 study. Thereafter the subject enters the C87080 study and will be further treated with 200 mg Certolizumab Pegol every two weeks.; Other Names: Cimzia; CDP870

Outcome Measures

Primary Outcome Measures :

1. Percentage of Subjects Reporting At Least One Treatment-emergent Adverse Event (TEAE) During The Study Period [ Time Frame: From Entry Visit up to approximately 144 weeks ]
   A TEAE is defined as any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any phase of a clinical trial including Pretreatment, Run-In, Wash-Out, or Follow-Up Phases. A TEAE is defined as being independent of assumption of any causality (eg, to trial or concomitant medication, primary or concomitant disease, or trial design). TEAEs are all AEs in which the onset and time is after the first study drug administration in C87080, up to 70 days after the last injection.
2. Percentage of Subjects With At Least One Treatment-emergent Serious Adverse Event (SAE) During The Study Period [ Time Frame: From Entry Visit up to approximately 144 weeks ]
   A Serious Adverse Event is any untoward medical occurrence that at any dose results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect.

Secondary Outcome Measures :

1. Percentage of Subjects With DAS28[ESR] (Disease Activity Score 28 [Erythrocyte Sedimentation Rate]) Remission (DAS28[ESR] < 2.6) at Completion/Withdrawal Visit [ Time Frame: Completion/Withdrawal Visit (up to approximately Week 136) ]
   DAS28(ESR) is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. < 2.6 (Remission), > = 2.6 - < =3.2 Low, > 3.2 - < = 5.1 Moderate, > 5.1 High.
2. Percentage of Subjects With CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Completion/Withdrawal Visit [ Time Frame: Completion/Withdrawal Visit (up to approximately Week 136) ]
   CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. A lower CDAI score indicating improvement in activity and a higher score indicating a decline activity.
3. Percentage of Subjects With SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Completion/Withdrawal Visit [ Time Frame: Completion/Withdrawal Visit (up to approximately Week 136) ]
   SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. <= 3.3 (Remission), >3.3 - <= 11 Low, > 11 - <= 26 Moderate, > 26 High.
4. Percentage of Subjects With ACR20 (American College of Rheumatology 20 % Improvement) Response at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   ACR20 response is defined for 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, 4) Patient's Global Assessment of Disease Activity, 5) Physician's Global Assessment of Disease Activity.
5. Percentage of Subjects With ACR50 (American College of Rheumatology 50 % Improvement) Response at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   ACR50 response is defined for subjects with at least 50 % 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, 4) Patient's Global Assessment of Disease Activity, 5) Physician's Global Assessment of Disease Activity.
6. Percentage of Subjects With ACR70 (American College of Rheumatology 70 % Improvement) Response at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   ACR70 response is defined for subjects with at least 70 % 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, 4) Patient's Global Assessment of Disease Activity, 5) Physician's Global Assessment of Disease Activity.
7. Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living activities (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Thus, the mean also has a range from 0-3. Change from Baseline is computed as the value at Completion/Withdrawal minus the Baseline value. A negative value in change from Baseline indicates an improvement.
8. Change From Baseline in PtAAP (Patient's Assessment of Arthritis Pain) at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   Change from Baseline in Patient's Assessment of Arthritis Pain - Visual Analog Scale (VAS) (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Completion/Withdrawal minus the Baseline value. A negative value in change from Baseline indicates an improvement.
9. Change From Baseline in FAS (Fatigue Assessment Scale) at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
   Change from Baseline in Fatigue Assessment Scale (0 to 10, 0 is "No Fatigue" and 10 is "Fatigue as bad as you can imagine") is computed as the value at Completion/Withdrawal minus the Baseline value. A negative value in change from Baseline indicates an improvement.
10. Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Completion/Withdrawal Visit [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to Week approximately 136) ]
    Change from Baseline in Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS) (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Completion/Withdrawal minus the Baseline value. A negative value in change from Baseline indicates an improvement.
11. Geometric Mean of Plasma Concentration of Certolizumab Pegol at Week 24 Visit [ Time Frame: Week 24 ]
    Plasma Samples for determination of Certolizumab Pegol were taken prior to Certolizumab Pegol administration. Values below the limit of quantification of 0.41 μg/mL will be set to half the limit of quantification for the summaries (0.205 μg/mL).
12. Percentage of Subjects With Positive Anti-Certolizumab Pegol (CZP) Antibody Status at Any Time From Baseline of the Feeder Study C87076 to the Completion/Withdrawal Visit of the Extension Study [ Time Frame: Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136) ]
    Antibody positive is defined as Anti-CZP antibody levels > 2.4 units/mL at any visit.
13. Percentage of Subjects Willing to Self-inject at Week 0 [ Time Frame: Week 0 of this study (C87080 [NCT00843778]) ]
    The percentage of subjects willing to self-inject at Week 0 will be presented using the Full Analysis Set.
14. Mean PRE-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 0 [ Time Frame: Week 0 of this study (C87080 [NCT00843778]) ]
    The three domains of the PRE SIAQ are feelings about injections, self-confidence, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting completed this pre-self-injection questionnaire. The PRE-SIAQ is taken before the subject's first injection.
15. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 0 [ Time Frame: Week 0 of this study (C87080 [NCT00843778]) ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
16. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 2 [ Time Frame: Week 2 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
17. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 4 [ Time Frame: Week 4 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
18. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 6 [ Time Frame: Week 6 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
19. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 8 [ Time Frame: Week 8 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
20. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 10 [ Time Frame: Week 10 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
21. Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 12 [ Time Frame: Week 12 ]
    The six domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.
22. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 0 [ Time Frame: Week 0 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
23. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 2 [ Time Frame: Week 2 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
24. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 4 [ Time Frame: Week 4 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
25. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 6 [ Time Frame: Week 6 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
26. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 8 [ Time Frame: Week 8 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
27. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 10 [ Time Frame: Week 10 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.
28. Mean Injection Site Reaction Questionnaire (ISRQ) Score at Week 12 [ Time Frame: Week 12 ]
    The ISRQ is scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Scores range from 0 to 10. Subjects receiving hospital nurse injection at this visit completed the ISRQ questionnaire.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with established adult rheumatoid arthritis on Disease Modifying Anti-Rheumatic Drugs (DMARDs) therapy who were included in C87076 protocol and:
• either failed to achieve remission after 6 months of study treatment
• or flared after the 6 months of study treatment and completed the study (C87076 [NCT00674362])

Exclusion Criteria:

• All the concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
• Previous clinical trials and previous biological therapy that could interfere with the results in the present clinical trial

Contacts and Locations

Locations

Austria

6

Wien, Austria

France

11

Rennes, France

64

Toulouse, France

10

Tours, France

Germany

17

Berlin, Germany

47

Berlin, Germany

20

Erlangen, Germany

50

Essen, Germany

16

Frankfurt, Germany

19

Heidelberg, Germany

15

Herne, Germany

24

Ratingen, Germany

18

Vogelsang-Gommern, Germany

23

Wuerzburg, Germany

Italy

29

Pavia, Italy

34

Roma, Italy

Poland

58

Bydgoszcz, Poland

67

Elblag, Poland

62

Lublin, Poland

55

Poznan, Poland

65

Poznan, Poland

60

Sopot, Poland

57

Szczecin, Poland

69

Torun, Poland

53

Warszawa, Poland

Sponsors and Collaborators

UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

More Information

Additional Information:

FDA Safety Alerts and Recalls 

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00843778
• Other Study ID Numbers: C87080; 2007-000830-38 ( EudraCT Number )
• First Posted: February 13, 2009
• Results First Posted: October 31, 2013
• Last Update Posted: January 30, 2014
• Last Verified: January 2014

Keywords provided by UCB Pharma:

Rheumatoid Arthritis; Moderate to Low Disease Activity; Certolizumab Pegol

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Certolizumab Pegol; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents