A Long-Term Extension Study to WA19926 (NCT01007435) of Tocilizumab in Participants With Early, Moderate to Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

A Multicenter, Open-Label, Single Arm, Long-Term Extension Study of WA19926 to Describe Safety During Treatment With Tocilizumab in Patients With Early, Moderate to Severe Rheumatoid Arthritis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01665430
• Other study ID #: ML28175
• Secondary ID: 2012-000172-42
• Status: Terminated
• Phase: Phase 3
• First received: August 13, 2012
• Last updated: February 7, 2018
• Start date: July 2012
• Est. completion date: February 2015

Study information

• Verified date: February 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, open-label, single arm long-term extension of study WA19926 will evaluate the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with early, moderate to severe rheumatoid arthritis who have completed the WA19926 core study. Eligible participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks for up to 104 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants who complete WA19926 core study (visit at Week 104 and two follow-up telephone visits) and who may benefit from study drug treatment according to the Investigator's assessment

• No current or recent adverse event or laboratory finding preventing the use of the study drug dose of tocilizumab 8 mg/kg at baseline visit

• Receiving treatment on an outpatient basis

• Females of child-bearing potential must agree to use at least one adequate method of contraception as defined by protocol during the treatment period

Exclusion Criteria:

• Pregnant women

• Participants who have prematurely withdrawn from the WA19926 study for any reason

• Treatment with any investigational agent or cell depleting therapies since last administration of study drug in the WA19926 core study

• Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL)1 agent, or a T-cell co-stimulation modulator since the last administration of the study drug in the WA19926 core study

• Immunization with a live/attenuated vaccine since the last administration of study drug in the WA19926 core study

• Diagnosis since visit at Week 104 of the core WA19926 study of rheumatic autoimmune disease other than rheumatoid arthritis

• Diagnosis since visit at Week 104 of the core WA19926 study of inflammatory joint disease other than rheumatoid arthritis

• Evidence of serious uncontrolled concomitant disease or disorder

• Known active or history of recurrent infection

• Current liver disease as determined by Investigator

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
Tocilizumab will be administered at 8 mg/kg intravenous infusion every 4 weeks, up to 104 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs include serious as well as non-serious AEs. AEs of special interest included: Infections including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives; Myocardial infarction/acute coronary syndrome; Gastrointestinal perforations and related events; Malignancies; Anaphylaxis/Hypersensitivity reactions; Demyelinating disorders; Stroke; Bleeding events; and Hepatic events.	Baseline up to 112 weeks
Secondary	Change From Baseline in Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Score	DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, erythrocyte sedimentation rate (ESR, in millimeters per hour [mm/hour]) and patient global assessment (PtGA) of disease activity (participant rated arthritis activity assessment on a 0 to 100 millimeter [mm] visual analog scale [VAS]; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Secondary	Change From Baseline in Total Tender Joint Counts (28 Joints)	The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 28 joints and joints were classified as tender/not tender giving a total possible tender joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Secondary	Change From Baseline in Total Swollen Joint Counts (28 Joints)	The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 28 joints and were classified as swollen/not swollen giving a total possible swollen joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Secondary	Percentage of Participants With Drug-Free Remission	Drug-free remission was defined as having clinical remission (defined as DAS28-ESR score <2.6) for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.	Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Secondary	Percentage of Participants With Clinical Remission	Clinical remission was defined as having DAS28-ESR score <2.6 at any point during the study. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.	Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Secondary	Time to Rheumatoid Arthritis (RA) Flare in Participants Who Had Entered Drug-Free Remission	Time to RA flare was defined as the period of drug-free remission (having DAS28-ESR score <2.6 for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit) until documented RA flare. RA flare was defined as any worsening of the participant's disease activity that, in the opinion of the Investigator, required treatment intensification beyond supportive therapy which could include restarting the study drug.	Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Secondary	Change From Baseline in Physician's Global Assessment (PGA) of Disease Activity Using Visual Analog Scale (VAS)	The PGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Secondary	Change From Baseline in PtGA of Disease Activity Using VAS	The PtGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Secondary	Change From Baseline in Participant Assessment of Pain Using VAS	Severity of pain was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the severity of pain that they had experienced because of their RA, ranging from 0 mm (no pain) to 100 mm (unbearable pain). Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Secondary	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	The HAQ-DI was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ-DI scale was an average of all the scores from all questions and ranged from 0 to 3, where higher scores represented higher disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from study for reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)