Rheumatoid ArthritisPhase 4DoseFlexNCT00580840
Dosing Flexibility Study in Patients With Rheumatoid Arthritis
A Phase 4 study testing Certolizumab pegol in people with Rheumatoid Arthritis, run by UCB Pharma at 66 sites in 3 countries.
Trial summary
During the run-in period, CZP will be administered at 400 mg (2 injections) at Wks 0, 2, and 4 and 200 mg with placebo (1 injection placebo, 1 injection CZP) at Wks 6, 8, 10, 12, 14 and 16. At Wk 18 patients will be grouped as responders or non-responders based on results of the ACR20 at Week 16. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Certolizumab pegol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 333 participants
- Where
- 66 sitesin 3 countries
- Study dates
- Dec 2007to Mar 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with established adult rheumatoid arthritis currently on Methotrexate for at least 3 months
Who cannot join
- All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
- Previous clinical trials participation and previous biological therapy that could interfere with the results of the present clinical trial
Trial locations and contacts
66 sites in 3 countries.
66 sites in 3 countries
United States50 sites
Study site
Albany, New York
Study site
Aventura, Florida
Study site
Bogart, Georgia
Study site
Charlotte, North Carolina
Study site
Clearwater, Florida
Study site
Cleveland, Ohio
Study site
Colorado Springs, Colorado
Study site
Dallas, Texas
Study site
Duncansville, Pennsylvania
Study site
Gainesville, Florida
Study site
Gilbert, Arizona
Study site
Haverhill, Massachusetts
Study site
Huntington Beach, California
Study site
Huntsville, Alabama
Study site
Jacksonville, Florida
Study site
Jupiter, Florida
Study site
Kansas City, Missouri
Study site
La Jolla, California
Study site
Las Vegas, Nevada
Study site
Lexington, Kentucky
Study site
Lincoln, Nebraska
Study site
Little Rock, Arkansas
Study site
Los Angeles, California
Study site
Melbourne, Florida
Study site
Mineola, New York
Study site
Monroe, North Carolina
Study site
Montgomery, Alabama
Study site
Morton Grove, Illinois
Study site
Norman, Oklahoma
Study site
Oklahoma City, Oklahoma
Study site
Palm Desert, California
Study site
Paradise Valley, Arizona
Study site
Perrysburg, Ohio
Study site
Pittsfield, Massachusetts
Study site
Portland, Maine
Study site
Reno, Nevada
Study site
Rochester, Minnesota
Study site
Sacramento, California
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Sarasota, Florida
Study site
Simpsonville, South Carolina
Study site
Sugar Land, Texas
Study site
Syracuse, New York
Study site
Tucson, Arizona
Study site
Tyler, Texas
Study site
Vancouver, Washington
Study site
Vernon Hills, Illinois
Study site
Wilmington, North Carolina
Study site
Worcester, Massachusetts
France9 sites
Study site
Bobigny
Study site
Le Havre
Study site
Lille
Study site
Limoges
Study site
Montivilliers
Study site
Nice
Study site
Paris
Study site
Perpigan
Study site
Saint-Etienne
Canada7 sites
Study site
Burlington, Ontario
Study site
Saint Catherine's, Ontario
Study site
Saskatoon, Saskatchewan
Study site
St. John's, Newfoundland and Labrador
Study site
Toronto, Ontario
Study site
Victoria, British Columbia
Study site
Winnipeg, Manitoba
About this study
Official title: A Phase IIIb Open-label run-in Double-blind, Placebo Controlled, Randomized Study to Evaluate the Safety/Efficacy of Certolizumab Pegol Administered Concomitantly With Stable-dose Methotrexate in Patients With Active Rheumatoid Arthritis.
During the run-in period, CZP will be administered at 400 mg (2 injections) at Wks 0, 2, and 4 and 200 mg with placebo (1 injection placebo, 1 injection CZP) at Wks 6, 8, 10, 12, 14 and 16. At Wk 18 patients will be grouped as responders or non-responders based on results of the ACR20 at Week 16.
Read the detailed description
Subjects with a stable methotrexate (MTX) dose enter the run-in period in which certolizumab pegol (CZP) will be administered at a dose of 400 mg (2 injections) at Weeks 0, 2, and 4 and at a dose of 200 mg with placebo (1 injection placebo, 1 injection CZP) at Weeks 6, 8, 10, 12, 14 and 16. The dose of MTX should be stable for at least 2 months prior to the Baseline visit and will remain stable throughout the trial, unless there is a need to reduce the dose for reasons of toxicity.
At the Week 18 visit, subjects who were ACR20 (American College of Rheumatology 20% Improvement) responders at Week 16 will be randomized in a double-blinded way to receive either 400 mg CZP given every 4 weeks and placebo given every 4 weeks given as two injections (alternating CZP and placebo every two weeks) plus MTX, 200 mg CZP and placebo administered every 2 weeks (one injection of each) plus MTX, or Placebo administered as two injections every 2 weeks plus MTX. Non-responders will be withdrawn from the study.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Certolizumab pegol, Placebo
- Keywords
- Rheumatoid Arthritis, Joint Disease, Arthritis, Certolizumab pegol, Cimzia
- Medical subject headings
- Arthritis, Rheumatoid, Joint Diseases, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certolizumab pegolDrug
Also called CZP, Cimzia
400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks)
Certolizumab pegolDrug
Also called CZP, Cimzia
200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each)
PlaceboOther
placebo (saline) administered as two injections every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Certolizumab pegol 400 mg and placebo | Active comparator | 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) Receives: Drug: Certolizumab pegol; Other: Placebo |
| Certolizumab pegol 200 mg and placebo | Experimental | 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) Receives: Drug: Certolizumab pegol; Other: Placebo |
| Placebo | Placebo comparator | Placebo administered as two injections every 2 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 34
Secondary outcomes (35)
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 16
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients
ACR50 responders are 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-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 16
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients
ACR70 responders are 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-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 16
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients
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. 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
Measured: Baseline, Week 16
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients
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
Measured: Baseline, Week 16
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients
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.
Measured: Baseline, Week 16
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients
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. 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
Measured: Week 16
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients
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
Measured: Week 16
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients
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 approvement in activity and a higher score indicating a decline activity.
Measured: Week 16
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients
Ratio is defined as the CRP value at Week 16 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Measured: Baseline, Week 16
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients
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 Week 16 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.
Measured: Baseline, Week 16
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18
ACR50 responders are 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-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 34
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18
ACR70 responders are 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-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Measured: Baseline, Week 34
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18
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. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward.
< 2.6 Remission,
> = 2.6 - < =3.2 Low, > 3.2 - < = 5.1 Moderate, > 5.1 High
Measured: Baseline, Week 34
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
<= 3.3 Remission, > 3.3 - <= 11 Low, > 11 - <= 26 Moderate, > 26 High
Measured: Baseline, Week 34
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18
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. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. Range for CDAI is 0-76 with a lower CDAI score reflects approvement in activity and a higher score reflects a decline.
Measured: Baseline, Week 34
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18
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. 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
Measured: Week 34
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18
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
Measured: Week 34
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18
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 approvement in activity and a higher score indicating a decline activity.
Measured: Week 34
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18
Ratio is defined as the CRP value at Week 34 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval.
Measured: Baseline, Week 34
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18
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 Week 34 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18
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 Week 34 minus the Baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18
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 an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18
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 Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18
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 Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Measured: Baseline, Week 34
Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18.
ACR20 loss are subjects with <20% improvement from Baseline for tender joint count, swollen joint count, and at least 3/5 core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein, 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 at 2 consecutive visits. Subjects losing response for 2 consecutive visits are considered as having the event on the day of the visit where response was first lost.
Measured: Week 18 up to Week 34
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionDec 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 333 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Clinical Trial Call Center, Study director, +1 877 822 9493
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00580840
- Sponsor's protocol ID
- C87077
- Other IDs
- 2007-005288-86
- Acronym
- DoseFlex
- Status last verified
- Mar 2012
- First submitted
- 21 Dec 2007
- Last updated
- 2 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
Furst DE, Shaikh SA, Greenwald M, Bennett B, Davies O, Luijtens K, Staelens F, Koetse W, Bertin P. Two dosing regimens of certolizumab pegol in patients with active rheumatoid arthritis. Arthritis Care Res (Hoboken). 2015 Feb;67(2):151-60. doi: 10.1002/acr.22496.
PubMed 25302624
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb Open-label run-in Double-blind, Placebo Controlled, Randomized Study to Evaluate the Safety/Efficacy of Certolizumab Pegol Administered Concomitantly With Stable-dose Methotrexate in Patients With Active Rheumatoid Arthritis.
- ClinicalTrials.gov ID
- NCT00580840
- Acronym / sponsor ID
- DoseFlex / C87077
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Joint Disease, Arthritis, Certolizumab pegol, Cimzia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 333 participants (actual)
- Lead sponsor
- UCB PharmaIndustry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 27 Dec 2007 (estimated)
- Results
- Posted 19 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
During the run-in period, CZP will be administered at 400 mg (2 injections) at Wks 0, 2, and 4 and 200 mg with placebo (1 injection placebo, 1 injection CZP) at Wks 6, 8, 10, 12, 14 and 16. At Wk 18 patients will be grouped as responders or non-responders based on results of the ACR20 at Week 16.
Detailed description
Subjects with a stable methotrexate (MTX) dose enter the run-in period in which certolizumab pegol (CZP) will be administered at a dose of 400 mg (2 injections) at Weeks 0, 2, and 4 and at a dose of 200 mg with placebo (1 injection placebo, 1 injection CZP) at Weeks 6, 8, 10, 12, 14 and 16. The dose of MTX should be stable for at least 2 months prior to the Baseline visit and will remain stable throughout the trial, unless there is a need to reduce the dose for reasons of toxicity.
At the Week 18 visit, subjects who were ACR20 (American College of Rheumatology 20% Improvement) responders at Week 16 will be randomized in a double-blinded way to receive either 400 mg CZP given every 4 weeks and placebo given every 4 weeks given as two injections (alternating CZP and placebo every two weeks) plus MTX, 200 mg CZP and placebo administered every 2 weeks (one injection of each) plus MTX, or Placebo administered as two injections every 2 weeks plus MTX. Non-responders will be withdrawn from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Certolizumab pegol 400 mg and placebo | Active comparator | Drug: Certolizumab pegol, Other: Placebo400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) |
| Certolizumab pegol 200 mg and placebo | Experimental | Drug: Certolizumab pegol, Other: Placebo200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo administered as two injections every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with established adult rheumatoid arthritis currently on Methotrexate for at least 3 months
Key exclusion criteria (2 listed)
- All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
- Previous clinical trials participation and previous biological therapy that could interfere with the results of the present clinical trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Certolizumab pegolAlso: CZP, Cimzia400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) | Drug | Certolizumab pegol 400 mg and placebo |
| Certolizumab pegolAlso: CZP, Cimzia200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) | Drug | Certolizumab pegol 200 mg and placebo |
| Placeboplacebo (saline) administered as two injections every 2 weeks | Other | Certolizumab pegol 200 mg and placebo, Certolizumab pegol 400 mg and placebo, Placebo |
Primary outcome
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
35 secondary outcomes
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients
Time frame: Baseline, Week 16
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients
Time frame: Baseline, Week 16
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients
Time frame: Baseline, Week 16
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients
Time frame: Baseline, Week 16
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients
Time frame: Baseline, Week 16
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients
Time frame: Baseline, Week 16
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients
Time frame: Week 16
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients
Time frame: Week 16
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients
Time frame: Week 16
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients
Time frame: Baseline, Week 16
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients
Time frame: Baseline, Week 16
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18
Time frame: Week 34
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18
Time frame: Week 34
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18
Time frame: Week 34
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18
Time frame: Baseline, Week 34
Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18.
Time frame: Week 18 up to Week 34
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25302624Furst DE, Shaikh SA, Greenwald M, Bennett B, Davies O, Luijtens K, Staelens F, Koetse W, Bertin P. Two dosing regimens of certolizumab pegol in patients with active rheumatoid arthritis. Arthritis Care Res (Hoboken). 2015 Feb;67(2):151-60. doi: 10.1002/acr.22496.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Clinical Trial Call Center study director
+1 877 822 9493
66 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Certolizumab pegol in people with Rheumatoid Arthritis, run by UCB Pharma at 66 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States, France, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18 (time frame: Baseline, Week 34). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00580840, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2018.