Open Label Extension for Patients Coming From the Dosing Flexibility Study in Patients With Rheumatoid Arthritis (RA)

Rheumatoid Arthritis Clinical Trial

— Dose Flex II  

Official title:

A Phase IIIb, Multi-center Open-label, Follow-up Study to Evaluate the Safety and Efficacy of Certolizumab Pegol Administered Concomitantly With Methotrexate in Patients With Active Rheumatoid Arthritis Who Participated in C87077.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00753454
• Other study ID #: C87084
• Secondary ID: 2007-005267-10
• Status: Completed
• Phase: Phase 3
• Start date: September 2008
• Est. completion date: May 2011

Study information

• Verified date: July 2012
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to continue to assess the safety of certolizumab pegol in combination with methotrexate (MTX).

Description:

Patients having completed the week 34 assessment in the C87077 (NCT00580840) study or having met the pre-defined criteria for flare (defined as patients that have randomized at Week 18 and experienced at 2 consecutive visits between Week 18 and Week 34 inclusive an equal to Baseline (W0) or worst swollen and tender joints counts), will be given the option to enroll in C87084 and receive certolizumab pegol [400 mg at Entry, Week 2, and Week 4 followed by 200 mg every two weeks (Q2W)] in combination with MTX until the drug is commercially available for the indication of Rheumatoid Arthritis (RA) in the patient's country or region or until further notice from UCB.

All patients will continue their MTX treatment at the same stable dose as during the C87077 (NCT00580840) study, unless there is a need to reduce the dose for reasons for toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must be able to understand the written Informed Consent Form (ICF)

• Patients must have achieved an ACR20 (American College of Rheumatology) response at Week 16 and completed the entire C87077 (NCT00580840) study or patients having been randomized at Week 18 and having met the pre-defined criteria for flare

• Patients must have complied with the protocol requirements during their participation in C87077 (NCT00580840)

• Female patients of childbearing potential must have a negative urine pregnancy test at Entry and must continue to have negative urine pregnancy tests throughout their study participation

• Patients must be willing to comply with protocol

Exclusion Criteria:

• Patients must not have a diagnosis of any other inflammatory Arthritis

• Patients must not have a secondary, non-inflammatory type of Arthritis that in the investigator's opinion is symptomatic enough to interfere with the evaluation of the study drug on the patient's primary diagnosis of Rheumatoid Arthritis (RA)

• Patients must not have a history of an infected joint prosthesis with that prosthesis still in situ

• Patients who do not meet the Medical History Exclusion criteria, as defined per protocol. Examples of exclusionary criteria (not all-inclusive): pregnancy, chronic infection, active Tuberculosis (TB), high risk of infection, Lymphproliferative Disorder, acute or chronic Viral Hepatitis B or C, known Human Immunodeficiency Virus (HIV), Malignancy or history of Malignancy, history of severe, progressive, and/or uncontrolled Renal, Hepatic, Hematological, Gastrointestinal, Endocrine, Pulmonary, Cardiac, Neurological or Cerebral Disease

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Certolizumab pegol
Liquid certolizumab pegol administered every two weeks as a single injection (400 mg at Entry, Week 2 & Week 4, followed by 200 mg every 2 weeks).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Canada, 

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 date and time is after the first study drug administration in C87084, up to 84 days after the last injection.	From Entry Visit up to approximately 60 weeks
Primary	Percentage of Subjects Withdrawing From Study Due To A 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 date and time is after the first study drug administration in C87084, up to 84 days after the last injection.	From Entry Visit up to approximately 60 weeks
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 60 weeks
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 C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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 C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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 C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in DAS28[ESR] (Disease Activity Score 28 [Erythrocyte Sedimentation Rate]) 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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.; < 2.6 Remission,; > = 2.6 - < =3.2 Low, > 3.2 - < = 5.1 Moderate, > 5.1 High.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in SDAI (Simplified Disease Activity Index) 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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.; <= 3.3 Remission, > 3.3 - <= 11 Low, > 11 - <= 26 Moderate, > 26 High.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in CDAI (Clinical Disease Activity Index) 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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.; The range for the CDAI is 0 - 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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. Missing values were imputed using Non-Responder Imputation (NRI).; < 2.6 (Remission),; > = 2.6 - < =3.2 Low, > 3.2 - < = 5.1 Moderate, > 5.1 High.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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. Missing values were imputed using Non-Responder Imputation (NRI).; <= 3.3 (Remission), > 3.3 - <= 11 Low, > 11 - <= 26 Moderate, > 26 High.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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. Missing values were imputed using Non-Responder Imputation (NRI).; The range for the CDAI is 0 - 76 with a lower CDAI score indicating improvement in activity and a higher score indicating a decline activity.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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 actives (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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Completion/Withdrawal Visit	There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Completion/Withdrawal Visit	PCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from 1 to 81, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
Secondary	Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Completion/Withdrawal Visit	MCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from -9 to 82, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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-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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)
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-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. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.	Baseline (in C87077 [NCT00580840]) to Completion/Withdrawal Visit (up to approximately 54 weeks)

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