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

• ClinicalTrials.gov Identifier: NCT01772316
• Recruitment Status: Completed
• First Posted: January 21, 2013
• Results First Posted: August 29, 2016
• Last Update Posted: November 6, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: December 2012
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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 Name: Roactemra

Outcome Measures

Primary Outcome Measures :

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 Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response [ Time Frame: Baseline up to follow-up (Week 104) ]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

Secondary Outcome Measures :

1. Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96 [ Time Frame: Week 48, Week 96 ]
2. 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) ]
3. Patient Global Visual Analog Score (VAS) at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ]
   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.
4. Patient Pain VAS Score at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ]
   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.
5. Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points [ Time Frame: Baseline, Week 48, Week 96 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: ML28488; 2012-002632-87 ( EudraCT Number )
• First Posted: January 21, 2013
• Results First Posted: August 29, 2016
• Last Update Posted: November 6, 2016
• Last Verified: September 2016

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases