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

Phase 3
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT01063062
Lead Sponsor
Hoffmann-La Roche
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
107
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
tocilizumabtocilizumab [RoActemra/Actemra]Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
tocilizumabMethotrexateParticipants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease ActivityBaseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24)

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.

Time to DAS28 Low Disease Activity24 Weeks

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving DAS28 Clinically Significant ImprovementBaseline, Weeks 4, 8, 12, 16, 20, 24

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.

Time to DAS28 Clinically Significant Improvement24 Weeks

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.

Percentage of Participants Achieving DAS28 RemissionWeeks 4, 8, 12, 16, 20, 24

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.

Time to DAS28 Remission24 Weeks

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.

Disease Activity Score 28 (DAS28)Weeks 4, 8, 12, 16, 20, 24

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.

C-Reactive Protein (CRP)Weeks 4, 8, 12, 16, 20, 24

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).

Erythrocyte Sedimentation Rate (ESR)Weeks 4, 8, 12, 16, 20, 24

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).

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)24 Weeks

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.

Number of Participants With AE and SAE Related Discontinuation24 Weeks

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.

Number of Participants With Serious Infections24 Weeks

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.

Number of Participants With Elevated AST (SGOT) and ALT (SGPT)Week 24

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.

Number of Participants With Elevated Total Cholesterol According to ATPIII GuidelinesWeeks 0 (Baseline), 4, 8, 12, 16, 20, 24

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.

Number of Participants With Elevated HDL Cholesterol According to ATPIII GuidelinesWeeks 0 (Baseline), 4, 8, 12, 16, 20, 24

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.

Number of Participants With Elevated LDL Cholesterol According to ATPIII GuidelinesWeeks 0 (Baseline), 4, 8, 12, 16, 20, 24

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.

Number of Participants With Elevated Triglyceride According to ATPIII GuidelinesWeeks 0 (Baseline), 4, 8, 12, 16, 20, 24

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.

Trial Locations

Locations (9)

Banha Educational Hospital; Rheumatology

🇪🇬

Banha, Egypt

Kasr El Ainy Hospital; Rheumatology

🇪🇬

Cairo, Egypt

Manial Specialized Hospital; Rheumatology

🇪🇬

Cairo, Egypt

Bab El Sheereya Hospital; Rheumatology

🇪🇬

Cairo, Egypt

El Hussein University Hospital; Rheumatology

🇪🇬

Cairo, Egypt

Ain Shams University Hospital; Rheumatology

🇪🇬

Cairo, Egypt

Alexandria University Hospital; Rheumatology

🇪🇬

Alexandria, Egypt

Alexandria University

🇪🇬

Alexandria, Egypt

Kasr El Ainy Hospital

🇪🇬

Cairo, Egypt

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