An Extension Study of WA19926 of the Long-Term Safety of Tocilizumab (RoActemra/Actemra) in Patients 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: Completed

Administrative data

• NCT number: NCT01664598
• Other study ID #: ML28124
• Status: Completed
• Phase: Phase 3
• Start date: May 2012
• Est. completion date: June 2015

Study information

• Verified date: March 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult participants, >/= 18 years of age
• Participants who complete their last WA19926 core study visit (Week 104) 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 RoActemra/Actemra 8 mg/kg at baseline visit
• Women of childbearing potential must agree to use adequate contraception as defined by protocol during the treatment period

Exclusion Criteria:

• Pregnant females
• Participants who have withdrawn prematurely from the WA19926 core study for any reason
• Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926
• Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926
• Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926
• Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis
• Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
• Evidence of severe uncontrolled concomitant disease or disorder
• Known active or history of recurrent infections
• Active tuberculosis requiring treatment in the previous 3 years
• History of alcohol, drug or chemical abuse since inclusion in the WA19926 study

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
8 mg/kg administered intravenously (IV) every 4 weeks for 104 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESIs)	An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. AESIs included serious infections (including opportunistic infections) and abnormal liver function tests.	Up to 112 weeks
Primary	Percentage of Adverse Events (AEs) Leading to Dose Modification and AEs Leading to Study Withdrawal	An AE is any untoward medical occurrence in a study participant given administered a pharmaceutical product, regardless of the cause of the AE.	Up to 112 weeks
Primary	Percentage of Adverse Events With Severity as Mild, Moderate, and Severe		Up to 112 weeks
Secondary	Percent Change From Baseline in the Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Over Time	The DAS28-ESR Scale is a measure of a participant's disease activity. It is based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and erythrocyte sedimentation rate. DAS28-ESR is expressed as a score on a scale with a minimum score of 0 (low disease activity ) to a maximum score of 10 (high disease activity). A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Percent Change From Baseline in the Simplified Disease Activity Index (SDAI) Over Time	The Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC), based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter (cm) visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). 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. A negative mean percent change from baseline indicates a decrease in disease activity, and a positive mean percent change from baseline indicates an increase in disease activity.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Change From Baseline in Tender Joint Count 66 (TJC 66) Over Time	Number of tender joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Change From Baseline in Swollen Joint Count 66 (SJC 66) Over Time	Number of swollen joints was determined by examination of 66 joints, as assessed through pressure and passive joint motion during physical examination.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Percentage of Participants With Treatment-Free Remission According to DAS28-ESR/SDAI Remission Criteria	Treatment-free remission is remission at two consecutive assessment visits (every 12 weeks) after discontinuing study drug on the second assessment visit. Clinical remission is DAS28-ESR score <2.6 and/or SDAI score =3.3. The DAS28-ESR scale is a measure of a participant's disease activity based on tender joint count (28 joints), swollen joint count (28 joints), a participant's assessment of disease activity, and ESR. DAS28-ESR scored on a scale with a minimum score of 0 (low disease activity) to a maximum score of 10 (high disease activity). The SDAI is sum of TJC and SJC, based on a 28-joint assessment, patient and physician global assessment assessed on 0-10 centimeter visual analogue scale (VAS), where 0 = no disease activity and 10 = worst disease activity, and level of C-reactive protein (CRP, mg/dL). 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.	Up to 104 weeks
Secondary	Time to Rheumatoid Arthritis Recurrence in Participants Who Achieved Treatment-Free Remission	Time to rheumatoid arthritis (RA) recurrence = period from treatment-free remission to RA recurrence. RA recurrence was worsening of disease activity with treatment beyond supportive therapy.	Up to 104 weeks
Secondary	Percent Change in Participant's General Assessment of Disease Activity (Severity of Disease) VAS Over Time	The participant's overall assessment of their current disease activity was displayed on a 100-millimeter (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.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Percent Change in Participant's Assessment of Pain (VAS) Over Time	Participants' pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104
Secondary	Change From Baseline in Health Assessment Questionnaire (HAQ-DI) Score Over Time	The HAQ-DI 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 overall score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability.	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92 and 104