A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs (REMISSION)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01610791
First received: May 31, 2012
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

This open label, single arm study will assess the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with moderate to severe active rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra at a dose of 8 mg/kg intravenously every 4 weeks for 24 weeks (6 infusions).


Condition Intervention Phase
Rheumatoid Arthritis
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: A Single Arm, Open Label Study to Assess the Safety, Tolerability and Efficacy of Tocilizumab in Active Rheumatoid Arthritis Patients With Inadequate Response to the DMARDs (REMISSION Study)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: Yes ]
    Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, AEs leading to withdrawal, AEs leading to death, and treatment-related AEs.


Secondary Outcome Measures:
  • Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Percentage of participants discontinuing study treatment for any reason at every visit; causes of discontinuation in the summary included AEs, deaths, lost to follo-wup, AE and investigator decision and 'not determined'.

  • Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value [ Time Frame: Baseline through Week 24 ] [ Designated as safety issue: No ]
    The difference between baseline and highest values until Week 24 of ALT and AST. The values are measures as international units per liter (UI/L). The change was calculated as the value (highest) at a later timepoint up to Week 24, minus the value at Baseline.

  • Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values [ Time Frame: Baseline through Week 24 ] [ Designated as safety issue: No ]
    Levels of LDL and TC were measured in milligrams/deciliter (mg/dL). Change in LDL and TC were calculated as the value (highest) through Week 24, minus the value at Baseline.

  • Percentage of Participants With Lipid Elevations by Study Visit [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Lipid panel assessed included TC, triglycerides, high-density lipoprotein (HDL), and LDL. Elevations were categorized as follows: LDL cholesterol: Optimal equals (=) less than (<)100 mg/dL, Near optimal=100-129 mg/dL, Borderline high 130-159 mg/dL, High 160-189 mg/dL, Very High ≥190 mg/dL; Total cholesterol: Desirable <200 mg/dL, Borderline high 200-239 mg/dL, High ≥240 mg/dL; HDL cholesterol: Low <40 mg/dL, High ≥60 mg/dL; Triglycerides: Normal <150 mg/dL, Borderline high 150-199 mg/dL, High 200-499 mg/dL, and Very high ≥500 mg/dL.

  • Disease Activity Score Based on 28-Joint Count (DAS28) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (>)3.2 to less than or equal to (≤) 5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.

  • Percentage of Participants by DAS28 Response Category [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 =low disease activity, DAS28 >3.2 to ≤5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.

  • Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A reduction in DAS28 of at least 1.2 units was considered a clinically meaningful improvement.

  • Time to Achieve Clinically Meaningful Reduction in DAS28 [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    A clinically meaningful improvement in DAS28 was defined as a reduction of at least 1.2 units. Time to achieving clinically meanigful improvement was calculated as the number of days from the first infusion to the first achievement of reduction of 1.2 units in DAS28.

  • Percentage of Participants Achieving Remission (DAS28 <2.6) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants with a DAS28 score <2.6 were considered to have achieved remission.

  • Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The ACR response rates ACR20, ACR50, ACR70 are defined as ≥20%, ≥50%, ≥70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the following 5 assessments: Patient assessment of pain (VAS); Patient global assessment of disease activity (VAS); Investigator global assessment of disease activity (VAS); and acute phase response (ESR or CRP)

  • Swollen and Tender Joint Counts [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The following 28 joints were assessed by the physician for tenderness : metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The change in SJC and TJC was determined as the difference in values from baseline at each visit.

  • Health Assessment Questionnaire (HAQ) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    HAQ was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple-choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The change in HAQ was determined as the difference in values from baseline at each visit.

  • Patient Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no disease activity" (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "maximum disease activity" (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.

  • Physician's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The physician's assessment of the participant's current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "maximum disease activity". The Physician's Global Assessment of Disease Activity was completed by the Efficacy Assessor who could or could not be a physician. The change in Physician's Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.

  • Patient Assessment of of Pain (VAS) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The participant's assessment of their current level of pain was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no pain" and the right-hand extreme of the line (100 mm) was described as "unbearable pain". The change in participant's perception of pain was determined as the difference in values from baseline at each visit.

  • C-Reactive Protein (CRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    CRP is an acute phase inflammatory marker. Levels of CRP increase with inflammation. The change in CRP was determined as the difference in values from baseline and at each visit.

  • Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. The change in ESR was determined as the difference in values from baseline at each visit.


Enrollment: 121
Study Start Date: March 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, 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
  • Moderate to severe active rheumatoid arthritis (DAS28 > 3.2 at screening)
  • Inadequate response to DMARDs
  • 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 enrollment
  • Rheumatic autoimmune disease other than RA
  • American College of Rheumatology (ACR) functional class IV
  • Prior history of or current inflammatory joint disease other than RA
  • Previous treatment with any biologic drug that is used in the treatment of RA
  • Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
  • Pregnant or lactating women
  • Active current or history of recurrent infection, active TB within the previous 3 years, HIV infection
  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: NCT01610791

Locations
Morocco
Casablanca, Morocco, 20000
Fés, Morocco, 30000
Khouribga, Morocco, 14000
Kénitra, Morocco, 25000
Marrakech, Morocco, 40000
Meknés, Morocco, 50000
Rabat, Morocco, 10000
Salé, Morocco, 15045
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: NCT01610791     History of Changes
Other Study ID Numbers: ML22638
Study First Received: May 31, 2012
Results First Received: May 7, 2014
Last Updated: July 8, 2014
Health Authority: Morocco: Ministry of Health - Drugs and pharmacy department

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 31, 2014