A Study of Tocilizumab in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic DMARDs

An Open Label Study to Evaluate the Safety and Effect on Disease Activity of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARDs.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00810277

Enrollment

Registered

2008-12-18

Start date

2008-11-30

Completion date

2010-05-26

Last updated

2017-08-03

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 single arm study will assess the safety and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis who have an inadequate response to current non-biologic DMARDs. Patients will receive iv infusions of tocilizumab 8mg/kg every 4 weeks for a total of 6 infusions, either as monotherapy or in combination with their current non-biologic DMARDs.

Interventions

DRUGtocilizumab [RoActemra/Actemra]

8mg/kg iv every 4 weeks for 24 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

* adult patients, \>=18 years of age; * moderate to severe rheumatoid arthritis; * inadequate response to current non-biologic DMARDs

Exclusion criteria

* rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis; * previous treatment with other biologics.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	Baseline up to Week 24	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 included both serious as well as non-serious AEs.

Secondary

Measure	Time frame	Description
Disease Activity Score (DAS28)	Baseline, Weeks 4, 8, 12, 16, 20, and 24	DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR) (mm/hour) or C-reactive protein (CRP) (mg/dL), and general health (GH) status (measured on a 0 to 100 mm Visual Analogue Scale \[VAS\] where 0=no disease activity and 100=worst disease activity). DAS28 was calculated using following formulas: DAS28-ESR = 0.56\square root (sqrt) (TJC28) + 0.28\sqrt(SJC28) + 0.70\natural logarithm (ln) (ESR) + 0.014\GH of disease activity; DAS28-CRP = 0.56\sqrt(TJC28) + 0.28\sqrt(SJC28) + 0.36\ln(10\CRP+1) + 0.014\*GH of disease activity. DAS28-ESR was adopted to calculate DAS28 if effective ESR data was available; otherwise DAS28-CRP was adopted to calculate DAS28. Total score range: 0-10, higher score=more disease activity. DAS28 \<=3.2 implied low disease activity, DAS \>3.2 to 5.1 implied moderate disease activity and DAS \>5.1 implied high disease activity, and DAS28 \<2.6 = clinical remission.
Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6)	Weeks 4, 8, 12, 16, 20, and 24	DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) or CRP (mg/dL), and general health (GH) status (measured on a 0 to 100 mm Visual Analogue Scale \[VAS\] where 0=no disease activity and 100=worst disease activity). DAS28 was calculated using following formulas: DAS28-ESR = 0.56\square root (sqrt) (TJC28) + 0.28\sqrt(SJC28) + 0.70\natural logarithm (ln) (ESR) + 0.014\GH of disease activity; DAS28-CRP = 0.56\sqrt(TJC28) + 0.28\sqrt(SJC28) + 0.36\ln(10\CRP+1) + 0.014\*GH of disease activity. DAS28-ESR was adopted to calculate DAS28 if effective ESR data was available; otherwise DAS28-CRP was adopted to calculate DAS28. Total score range: 0-10, higher score=more disease activity. DAS28 \<=3.2 implied low disease activity, DAS \>3.2 to 5.1 implied moderate disease activity and DAS \>5.1 implied high disease activity, and DAS28 \<2.6 = clinical remission.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20% (ACR20), ACR50 and ACR70 Response	Weeks 4, 8, 12, 16, 20, and 24	ACR20, ACR50, and ACR70 response: greater than or equal to (\>=) 20 percent (%), 50%, and 70% improvement respectively, in tender or swollen joint counts and in 3 of the following criteria: (1) Participant's assessment of pain (measured on a 0 to 100 mm VAS where 0=no pain and 100=unbearable pain); (2) Participant's assessment of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity); (3) Investigator's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity); (4) Participant's assessment of functional disability via health assessment questionnaire (HAQ) (measured using 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do).
C-Reactive Protein (CRP) Level	Baseline, Weeks 4, 8, 12, 16, 20, and 24	—
Percentage of Participants Who Discontinued the Study	Up to Week 24	—
Percentage of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Level Elevation More Than 1.5 Times Upper Limit of Normal	Up to Week 24	Normal range of ALT is 7 to 56 units per liter (U/L) of serum. Normal range of AST is 5 to 40 units per liter (U/L) of serum.
Percentage of Participants With Lipid Level Elevations	Week 24	Low density lipoprotein (LDL) level was categorized as 'Optimal (less than \[\<\] 100 milligram per deciliter \[mg/dL\])', 'Near Optimal/Above Optimal (100-129 mg/dL)', 'Borderline High (130-159 mg/dL)', 'High (160-189 mg/dL)', and 'Very high (190 mg/dL)'. High density lipoprotein (HDL) level was categorized as 'Acceptable (40-59 mg/dL)', 'High (\>=60 mg/dL)'. Total cholesterol (TC) level was categorized as 'Desirable (\<200 mg/dL)', 'Borderline High (200-239 mg/dL)', 'High (\>=240 mg/dL)'.
Neutrophil Count	Baseline, Weeks 4, 8, and 12	—
Erythrocyte Sedimentation Rate (ESR)	Baseline, Weeks 4, 8, 12, 16, 20, and 24	The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells sediment in a period of one hour.

Countries

Finland

Participant flow

Participants by arm

Arm	Count
Tocilizumab Participants received tocilizumab at a dose of 8 milligram per kilogram (mg/kg) via intravenous infusion every 4 weeks up to 24 weeks.	14
Total	14

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1

Baseline characteristics

Characteristic	Tocilizumab
Age, Continuous	53.86 years STANDARD_DEVIATION 9.662
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	13 / 14
serious Total, serious adverse events	1 / 14

Outcome results

Primary

Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 included both serious as well as non-serious AEs.

Time frame: Baseline up to Week 24

Population: Analysis population included all participants who entered the study.

Arm	Measure	Group	Value (NUMBER)
Tocilizumab	Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	AEs	92.9 percentage of participants
Tocilizumab	Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	SAEs	7.1 percentage of participants

Secondary