A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01235507
First received: October 15, 2010
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

This open-label, single arm study will assess the safety and efficacy of RoActem ra/Actemra (tocilizumab) in combination with methotrexate in patients with activ e moderate to severe rheumatoid arthritis who have an inadequate response to dis ease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Act emra at a dose of 8 mg/kg (maximum 800 mg) intravenously every 4 weeks for a tot al of 6 infusions. Methotrexate will be continued at a stable dose. Anticipated time on study treatment is 24 weeks.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: methotrexate
Drug: tocilizumab [RoActemra/Actemra]
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: Actemra - Local Bosnian Open, Multicentric, Trial to Evaluate Safety, Tolerability and Efficacy of Tocilizumab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis After Inadequate Response to DMARDs

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overview of Adverse Events [ Time Frame: Screening Visit, Baseline, Weeks 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    Adverse Events (AEs), Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI) were recorded from the Screening Visit until the final visit at Week 24.


Secondary Outcome Measures:
  • Disease Activity Score 28 (DAS28) [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]

    DAS28 was calculated using the 28 joints count, the C-reactive protein levels (CRP) and participant's global assessment (PtGA) of disease activity .The following formula was used to determine DAS28.

    DAS28 (equals) = 0.56 × (square root of) √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100- millimeter [mm] visual analog scale [ VAS]).

    The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.


  • Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) [ Time Frame: Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    Participants were considered to be with low disease activity when DAS28 was less than or equal to (≤) 3.2 and in clinical remission when DAS28 scores were less than (<) 2.6

  • Swollen and Tender Joint Counts [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    66 and 68 joints were assessed by the physician for tenderness or swelling respectively . The joints were counted as tender/not tender and swollen/not swollen and scored. The scores ranged from 0 to 66 for TJC and 0 to 68 for SJC

  • Physician's Global Assessment of Disease Activity [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity

  • Participant's Global Assessment of Disease Activity [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    Participant's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity

  • Participant's Global Assessment of Pain [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    Participant's global assessment of pain was performed using a 100 mm VAS ranging from no pain (0) at the left edge to unbearable pain (100) at the right edge. The distance in mm from the left edge of the scale was measured.

  • C-Reactive Protein Levels [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    CRP is a marker of acute phase inflammation. Decrease in levels of CRP indicate improvement. CRP is measured in mg/L

  • Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Weeks 8, 16 and 24 ] [ Designated as safety issue: No ]
    ESR is a marker of inflammation. Decrease in levels of ESR indicate improvement.


Enrollment: 71
Study Start Date: February 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: methotrexate
stable dose as prescribed
Drug: tocilizumab [RoActemra/Actemra]
8 m/kg (maximum 800 mg) intravenously every 4 weeks for a total of 6 infusions

  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
  • Active moderate to severe rheumatoid arthritis (RA)
  • On methotrexate treatment (oral or parenteral) for at least 12 weeks, at stable dose of at least 15 mg/week for at least 6 weeks
  • Oral corticosteroids must have been at stable dose of </= 10 mg/day prednisone (or equivalent) for at least 25 out of 28 days prior to first dose of study drug
  • Body weight </= 150 kg

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months of study entry
  • Rheumatic autoimmune disease other than RA
  • Functional class IV according to American College of Rheumatology (ACR) classification
  • Prior history of or current inflammatory joint disease other then RA
  • Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
  • Treatment with any biologic drug that is used in the treatment or RA
  • Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
  • Known active current or history of recurrent infection
  • History of or currently active primary or secondary immunodeficiency
  • Positive for HIV
  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: NCT01235507

Locations
Bosnia and Herzegovina
Banja Luka, Bosnia and Herzegovina, 78 000
Sarajevo, Bosnia and Herzegovina, 71000
Tuzla, Bosnia and Herzegovina, 75000
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: NCT01235507     History of Changes
Other Study ID Numbers: ML25303
Study First Received: October 15, 2010
Results First Received: October 13, 2014
Last Updated: October 13, 2014
Health Authority: Bosnia: Agency for Drugs and Medical Devices of Bosnia and Herzegovina

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

ClinicalTrials.gov processed this record on October 21, 2014