A Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01772316
First received: January 17, 2013
Last updated: July 18, 2016
Last verified: July 2016
  Purpose
This multicenter, open-label, single arm, long-term extension study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in participants with moderate to severe rheumatoid arthritis who have completed the 97-week WA22762 or the 96-week NA25220 core study. Participants will receive RoActemra/Actemra 162 milligram (mg) subcutaneously weekly (for participants entering from WA22762) or every two weeks (for participants entering from NA25220) for 96 weeks, with telephone call follow-up visits at Weeks 100 and 104.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Long-term Extension Study of WA22762 and NA25220 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With an Adverse Event (AE) [ Time Frame: Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months) ] [ Designated as safety issue: No ]
    An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.

  • Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response [ Time Frame: Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months) ] [ Designated as safety issue: No ]
  • Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included swollen joint count (SJC), tender joint count (TJC), acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status (GH). For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC 28]) + (0.28 × √[SJC 28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 48 - DAS28-ESR at Baseline.

  • Change From Baseline in DAS28-ESR at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included SJC, TJC, acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status. For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC28]) + (0.28 × √[SJC28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 96 - DAS28-ESR at Baseline.

  • Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The SDAI was the numerical sum of five outcome parameter: SJC and TJC, Patient Global Assessment of Disease Activity (PGA) and Investigator Global Assessment of Disease Activity (IGA), and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 48 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. Here, n signifies the number of subjects evaluable at the specified time points.

  • Change From Baseline in SDAI at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    The SDAI was the numerical sum of five outcome parameter: SJC and TJC, PGA and IGA, and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 96 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.

  • Change From Baseline in Total Tender Joint Count (TJC) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement. Here, 'n' represents the number of participants with a measure at specified time point.

  • Change From Baseline in Total TJC at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement.

  • Change From Baseline in Swollen Joint Count (SJC) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A negative number indicated improvement.

  • Change From Baseline in SJC at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. Change in SJC = SJC at Week 96 - SJC at Baseline. A negative number indicated improvement.


Secondary Outcome Measures:
  • Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation [ Time Frame: Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months) ] [ Designated as safety issue: No ]
  • Patient Global Visual Analog Score (VAS) at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    This assessment represents the patient's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity.

  • Patient Pain VAS Score at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    This assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain.

  • Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Minimum score was 0, maximum score was 3. A smaller score indicated improvement.


Enrollment: 47
Study Start Date: December 2012
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab Subcutaneous (SC)
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
Drug: tocilizumab
162 mg subcutaneously weekly or every two weeks, 96 weeks
Other Name: Roactemra

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult participants, >/= 18 years of age
  • Participants who have completed the 97-week WA22762 or 96-week NA25220 core study on subcutaneous or intravenous RoActemra/Actemra and based on the investigator's judgment may continue to benefit from RoActemra/Actemra treatment in this study investigating the subcutaneous formulation
  • Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the maximum recommended dose are permitted if on a stable dose regimen for >/= 4 weeks prior to baseline
  • Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
  • Receiving treatment on an outpatient basis
  • Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception

Exclusion Criteria:

  • Participants who have prematurely withdrawn from the WA22762 or NA25220 core studies for any reason
  • Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
  • History of severe allergic or anaphylactic reactions to human, humanized or mural monoclonal antibodies
  • Evidence of serious uncontrolled concomitant disease
  • Current liver disease as determined by the principal investigator
  • History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
  • Known active current or history of recurrent infections
  • Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  • Active tuberculosis requiring treatment within the previous 3 years
  • Primary or secondary immunodeficiency (history of or currently active)
  • Pregnant or breast feeding women
  • Body weight > 150 kilogram (kg)
  • Inadequate renal, hepatic or hematologic function
  • Positive for hepatitis B or hepatitis C
  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: NCT01772316

Locations
Spain
Merida, Badajoz, Spain, 06800
Santander, Cantabria, Spain, 39008
La Coruna, La Coruña, Spain, 15006
Santiago De Compostela, La Coruña, Spain, 15706
La Laguna, Tenerife, Spain, 38320
Valenica, Valencia, Spain, 46009
Barakaldo, Vizcaya, Spain, 48903
Bilbao, Vizcaya, Spain, 48013
Madrid, Spain, 28007
Madrid, Spain, 28046
Malaga, Spain, 29009
Sevilla, Spain, 41009
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01772316     History of Changes
Other Study ID Numbers: ML28488  2012-002632-87 
Study First Received: January 17, 2013
Results First Received: July 18, 2016
Last Updated: July 18, 2016
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

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

ClinicalTrials.gov processed this record on August 28, 2016