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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01063062
First received: February 3, 2010
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: Methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity [ Time Frame: Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24) ] [ Designated as safety issue: No ]
    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 Activity [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants Achieving DAS28 Clinically Significant Improvement [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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 Improvement [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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 Remission [ Time Frame: Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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 Remission [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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 Discontinuation [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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 Infections [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 Guidelines [ Time Frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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 Guidelines [ Time Frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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 Guidelines [ Time Frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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 Guidelines [ Time Frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    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.


Enrollment: 107
Study Start Date: February 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tocilizumab
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.
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenous infusion every 4 weeks.
Drug: Methotrexate
methotrexate as per standard of care in clinical practice.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01063062

Locations
Egypt
Alexandria, Egypt
Banha, Egypt
Cairo, Egypt
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01063062     History of Changes
Other Study ID Numbers: ML22725
Study First Received: February 3, 2010
Results First Received: July 8, 2014
Last Updated: July 8, 2014
Health Authority: Egypt: Ministry of Health and Population

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014