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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01665430

Enrollment

Registered

2012-08-15

Start date

2012-07-31

Completion date

2015-02-28

Last updated

2018-02-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief 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.

Interventions

DRUGTocilizumab

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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* Pregnant women * Participants who have prematurely withdrawn from the WA19926 study for any reason * Treatment with any investigational agent or cell depleting therapies since last administration of study drug in the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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)	Baseline up to 112 weeks	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Total Tender Joint Counts (28 Joints)	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)	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.
Change From Baseline in Total Swollen Joint Counts (28 Joints)	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)	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.
Percentage of Participants With Drug-Free Remission	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])	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.
Percentage of Participants With Clinical Remission	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])	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.
Change From Baseline in Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Score	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)	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.
Change From Baseline in Physician's Global Assessment (PGA) of Disease Activity Using Visual Analog Scale (VAS)	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)	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.
Change From Baseline in PtGA of Disease Activity Using VAS	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)	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.
Change From Baseline in Participant Assessment of Pain Using VAS	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)	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.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)	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.
Time to Rheumatoid Arthritis (RA) Flare in Participants Who Had Entered Drug-Free Remission	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])	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.

Countries

Poland

Participant flow

Recruitment details

The study included participants with early, moderate to severe rheumatoid arthritis (RA) who had completed WA19926 (NCT01007435) core study and who may have benefited from tocilizumab treatment based on the Investigator's judgment.

Pre-assignment details

43 participants were initially screened but only 38 participants were enrolled, and started the study.

Participants by arm

Arm	Count
Tocilizumab Participants received tocilizumab 8 mg/kg IV infusion q4w up to 104 weeks.	38
Total	38

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Other Unspecified	2
Overall Study	Withdrawal by Subject	6

Baseline characteristics

Characteristic	Tocilizumab
Age, Continuous	52.3 years STANDARD_DEVIATION 12.12
Sex: Female, Male Female	32 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	22 / 38
serious Total, serious adverse events	3 / 38

Outcome results

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.

Time frame: Baseline up to 112 weeks

Population: ITT population

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)	AE	65.8 percentage of participants
Tocilizumab	Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)	AEs of Special Interest	34.2 percentage of participants
Tocilizumab	Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)	SAE	7.9 percentage of participants

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.

Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)