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

Rheumatoid Arthritis Clinical Trial

— CERTAIN 2  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00843778
• Other study ID #: C87080
• Secondary ID: 2007-000830-38
• Status: Completed
• Phase: Phase 3
• First received: January 5, 2009
• Last updated: January 17, 2014
• Start date: January 2009
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Paul-Ehrlich-InstitutAustria: Agency for Health and Food SafetyItaly: The Italian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.

Locations

Country	Name	City	State
Austria	6	Wien
France	11	Rennes
France	64	Toulouse
France	10	Tours
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
Italy	29	Pavia
Italy	34	Roma
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

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

Austria,  France,  Germany,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Reporting At Least One Treatment-emergent Adverse Event (TEAE) During The Study Period	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.	From Entry Visit up to approximately 144 weeks	No
Primary	Percentage of Subjects With At Least One Treatment-emergent Serious Adverse Event (SAE) During The Study Period	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.	From Entry Visit up to approximately 144 weeks	No
Secondary	Percentage of Subjects With DAS28[ESR] (Disease Activity Score 28 [Erythrocyte Sedimentation Rate]) Remission (DAS28[ESR] < 2.6) at Completion/Withdrawal Visit	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 v(TJC) + 0.28 x v(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.	Completion/Withdrawal Visit (up to approximately Week 136)	No
Secondary	Percentage of Subjects With CDAI (Clinical Disease Activity Index) Remission (CDAI =2.8) at Completion/Withdrawal Visit	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.	Completion/Withdrawal Visit (up to approximately Week 136)	No
Secondary	Percentage of Subjects With SDAI (Simplified Disease Activity Index) Remission (SDAI =3.3) at Completion/Withdrawal Visit	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.	Completion/Withdrawal Visit (up to approximately Week 136)	No
Secondary	Percentage of Subjects With ACR20 (American College of Rheumatology 20 % Improvement) Response at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Percentage of Subjects With ACR50 (American College of Rheumatology 50 % Improvement) Response at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Percentage of Subjects With ACR70 (American College of Rheumatology 70 % Improvement) Response at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Change From Baseline in PtAAP (Patient's Assessment of Arthritis Pain) at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Change From Baseline in FAS (Fatigue Assessment Scale) at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Completion/Withdrawal Visit	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.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to Week approximately 136)	No
Secondary	Geometric Mean of Plasma Concentration of Certolizumab Pegol at Week 24 Visit	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).	Week 24	No
Secondary	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	Antibody positive is defined as Anti-CZP antibody levels > 2.4 units/mL at any visit.	Baseline in the feeder study (C87076 [NCT00674362]) to Completion/Withdrawal Visit in the extension study (up to approximately Week 136)	No
Secondary	Percentage of Subjects Willing to Self-inject at Week 0	The percentage of subjects willing to self-inject at Week 0 will be presented using the Full Analysis Set.	Week 0 of this study (C87080 [NCT00843778])	No
Secondary	Mean PRE-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 0	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.	Week 0 of this study (C87080 [NCT00843778])	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 0	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.	Week 0 of this study (C87080 [NCT00843778])	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 2	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 4	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 6	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 8	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 10	No
Secondary	Mean POST-Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at 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.	Week 12	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 0	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 2	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 4	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 6	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 8	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 10	No
Secondary	Mean Injection Site Reaction Questionnaire (ISRQ) Score at 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.	Week 12	No

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