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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
  • Madrid, Spain, 28007
  • Malaga, Spain, 29009
  • Sevilla, Spain, 41009
  • Badajoz
    • Merida, Badajoz, Spain, 06800
  • Cantabria
    • Santander, Cantabria, Spain, 39008
  • La Coruña
    • La Coruna, La Coruña, Spain, 15006
    • Santiago De Compostela, La Coruña, Spain, 15706
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
  • Valencia
    • Valenica, Valencia, Spain, 46009
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
    • Bilbao, Vizcaya, Spain, 48013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Roactemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.	Baseline up to follow-up (Week 104)
Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response		Baseline up to follow-up (Week 104)
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48	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.	Baseline, Week 48
Change From Baseline in DAS28-ESR at Week 96	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.	Baseline, Week 96
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48	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.	Baseline, Week 48
Change From Baseline in SDAI at Week 96	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.	Baseline, Week 96
Change From Baseline in Total Tender Joint Count (TJC) at Week 48	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.	Baseline, Week 48
Change From Baseline in Total TJC at Week 96	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.	Baseline, Week 96
Change From Baseline in Swollen Joint Count (SJC) at Week 48	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.	Baseline, Week 48
Change From Baseline in SJC at Week 96	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.	Baseline, Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96		Week 48, Week 96
Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation		Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months)
Patient Global Visual Analog Score (VAS) at Specified Time Points	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.	Baseline, Week 48, Week 96
Patient Pain VAS Score at Specified Time Points	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.	Baseline, Week 48, Week 96
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points	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.	Baseline, Week 48, Week 96

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (Estimate): January 21, 2013

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: September 29, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML28488; 2012-002632-87 (EudraCT Number)