A Study With Tocilizumab [RoActemra/Actemra] Monotherapy or in Combination With Methotrexate in Patients With Rheumatoid Arthritis (PICTURE)

Rheumatoid Arthritis Clinical Trial

Official title:

A Single-arm, Open-label, Multicenter Study of Tocilizumab Monotherapy or in Combination With Methotrexate to Assess Safety and the Efficacy in Reducing Disease Activity in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Non-biologic DMARDs (PICTURE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01063062
• Other study ID #: ML22725
• Status: Completed
• Phase: Phase 3
• First received: February 3, 2010
• Last updated: July 8, 2014
• Start date: February 2010
• Est. completion date: January 2011

Study information

• Verified date: July 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Health and Population
• Study type: Interventional

Clinical Trial Summary

This single-arm, open-label, multicenter study evaluated the safety and tolerability and the efficacy in reducing disease activity of tocilizumab [RoActemra/Actemra] as monotherapy or in combination with methotrexate in patients with active moderate to severe rheumatoid arthritis (RA). Patients were eligible to participate in this study if they are currently experiencing an inadequate response to a stable dose of a non-biologic disease-modifying antirheumatic drug (DMARD). Patients received 8 mg/kg tocilizumab [RoActemra/Actemra] as an intravenous infusion every 4 weeks for a total of 6 infusions. The anticipated time on study treatment was 24 weeks. The target sample size was 50-200 patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients = 18 years of age

• Moderate to severe rheumatoid arthritis (RA) for at least 6 months (defined as a Disease Activity Score (DAS28) > 3.2 at screening)

• Patients with active RA after more than 12 weeks of treatment with DMARDs

• Patients with inadequate response to a stable dose of non-biologic DMARD

Exclusion Criteria:

• Autoimmune disease other than RA. Patients with interstitial pulmonary fibrosis and able to tolerate methotrexate (MTX) and patients with Sjögren's Syndrome and RA are permitted

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment

• Prior history of or current inflammatory joint disease other than RA

Study Design

Allocation: Non-Randomized, 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

Drug:
• tocilizumab [RoActemra/Actemra]
8 mg/kg intravenous infusion every 4 weeks.
• Methotrexate
methotrexate as per standard of care in clinical practice.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of < 3.2.	Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24)	No
Primary	Time to DAS28 Low Disease Activity	Time to DAS28 Low Disease Activity was defined as the time in days from the first infusion of study drug to the achievement of a DAS28 Score <3.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of < 3.2.	24 Weeks	No
Secondary	Percentage of Participants Achieving DAS28 Clinically Significant Improvement	DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.	Baseline, Weeks 4, 8, 12, 16, 20, 24	No
Secondary	Time to DAS28 Clinically Significant Improvement	Time to DAS28 Clinically Significant Improvement was the Time in days from the first infusion of study drug to the achievement of a DAS28 score reduction of at least 1.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of < 3.2.	24 Weeks	No
Secondary	Percentage of Participants Achieving DAS28 Remission	DAS28 Remission was defined as a DAS28 score < 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.	Weeks 4, 8, 12, 16, 20, 24	No
Secondary	Time to DAS28 Remission	Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score < 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.	24 Weeks	No
Secondary	Disease Activity Score 28 (DAS28)	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of < 3.2.	Weeks 4, 8, 12, 16, 20, 24	No
Secondary	C-Reactive Protein (CRP)	Blood was collected for C-Reactive Protein (CRP), a test for inflammation, at Weeks 4, 8, 12, 16, 20 and 24 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL).	Weeks 4, 8, 12, 16, 20, 24	No
Secondary	Erythrocyte Sedimentation Rate (ESR)	Blood was collected for Erythrocyte Sedimentation Rate (ESR), a test to assess inflammation, at Weeks 4, 8, 12, 16, 20, 24 and was analyzed at a central laboratory. ESR was measured in millimeters/hour (mm/hr).	Weeks 4, 8, 12, 16, 20, 24	No
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	24 Weeks	No
Secondary	Number of Participants With AE and SAE Related Discontinuation	The number of participants who stopped using the study drug because of an AE or a SAE. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	24 Weeks	No
Secondary	Number of Participants With Serious Infections	A serious infection was an infection that qualified as a Serious Adverse Event (SAE). A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	24 Weeks	No
Secondary	Number of Participants With Elevated AST (SGOT) and ALT (SGPT)	Blood was collected for aspartate aminotransferase (serum glutamic oxaloacetic transaminase) [AST/SGOT] and alanine aminotransferase (serum glutamic pyruvic transaminase) [ALT/SGPT], liver function tests, and were analyzed at a central laboratory. The number of participants with High AST (SGOT) or ALT (SGPT) levels at Week 24 is reported.	Week 24	No
Secondary	Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines	Blood samples were collected for Total Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Desirable ( < 200), Borderline High (200- 239) or High (= 240). The number of participants categorized Borderline High or High at each time-point is reported.	Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24	No
Secondary	Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines	Blood samples were collected for High Density Lipoprotein (HDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the HDL Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Low (< 40) or High (= 60). The number of participants with category High at each time-point is reported.	Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24	No
Secondary	Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines	Blood samples were collected for Low Density Lipoprotein (LDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the LDL Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Optimal (< 100), Near Optimal/Above Optimal (100- 129), Borderline High (130- 159), High (160-189) or Very High (= 190). The number of participants categorized Borderline High, High or Very High at each time-point is reported.	Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24	No
Secondary	Number of Participants With Elevated Triglyceride According to ATPIII Guidelines	Blood samples were collected for Triglyceride and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Triglyceride level in milligram/deciliter (mg/dL) was categorized as: Normal (< 150), Borderline High (150- 199), High (200- 499) or Very High (= 500). The number of participants categorized Borderline High, High or Very High at each time-point is reported.	Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24	No