A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.

Rheumatoid Arthritis Clinical Trial

Official title:

Local Open-label Multicenter Study to Evaluate the Quality of Life in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to DMARDs When Adding Tocilizumab (TCZ)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996203
• Other study ID #: ML22665
• Status: Completed
• Phase: Phase 4
• First received: October 15, 2009
• Last updated: February 28, 2018
• Start date: October 31, 2009
• Est. completion date: February 14, 2011

Study information

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

Clinical Trial Summary

This open-label single arm study will evaluate the efficacy and safety of tocilizumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDs. Patients will receive tocilizumab 8 mg/kg by intravenous infusion every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs at stable doses. Anticipated time on study treatment is 24 weeks, and the target sample size is 200.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: February 14, 2011
• Est. primary completion date: February 14, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients, >/= 18 years of age

• moderate to severe active rheumatoid arthritis of >/=6 months duration

• inadequate clinical response to current non-biologic DMARDs

• current DMARDs must be at stable dose for 8 weeks prior to study entry

• oral corticosteroids (</=10mg/day prednisone or equivalent) and NSAIDs must be at stable dose for >/=4 weeks prior to screening

Exclusion Criteria:

• rheumatic autoimmune disease other than RA

• history of or current inflammatory joint disease other than RA

• previous treatment with any biologic DMARD

• functional class IV as defined by the ACR classification

• intra-articular or parenteral corticosteroids within 6 weeks prior to screening

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• tocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks for 24 weeks
• DMARDs (disease-modifying antirheumatic drugs)
stable doses at investigator's prescription

Locations

Country	Name	City	State
Russian Federation	Chelyabinsk Regional Clinical Hospital; Rheumatology	Chelyabinsk
Russian Federation	Republican clinical hospital of Karachai-Cherkess; Rheumatologic Department	Cherkess
Russian Federation	Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"	Ekaterinburg
Russian Federation	Sverdlovsk Regional Clinical Hospital # 1; Rheumatology Dept	Ekaterinburg
Russian Federation	Irkutsk Regional Consulting and Diagnostic Clinical Center; Regional Center of Reumatolodic Deasise	Irkutsk
Russian Federation	Republican Clinicodiagnostic Center	Izhevsk
Russian Federation	Kaliningrad Regional Clinical Hospital; Rheumatologic Department	Kaliningrad
Russian Federation	War Veterans Regional Clinical Hospital;Therapy Department	Kemerovo
Russian Federation	Kirov Regional Clinical Hospital; Reumatology Department	Kirov
Russian Federation	GUZ Regional clinical hospital # 1	Krasnodar
Russian Federation	GMU Kursk regional clinical hospital	Kursk
Russian Federation	FGU Central Clinical Hospital with Polyclinic Administration President RF	Moscow
Russian Federation	FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"	Moscow
Russian Federation	FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences	Moscow
Russian Federation	Head Clinical Hospital of Internal Affair Ministry of Russia	Moscow
Russian Federation	Vladimirskiy Regional Scientific Research Inst.	Moscow
Russian Federation	SIH Nizhny Novgorod Regional Clinical Hospital n.a. Semashko	Nizhny Novgorod
Russian Federation	Republican Hospital Named After V.A. Baranov	Petrozavodsk
Russian Federation	Rostov State Medical University; Cardiorheumatology Department	Rostov-na-Donu
Russian Federation	Clinical hospital #1	Smolensk
Russian Federation	Surgut Region Clinical Hospital	Surgut
Russian Federation	Glpu Tjumen Regional Clinical Hospital #1	Tjumen
Russian Federation	Republican clinical hospital named after G.G. Kuvatov	UFA
Russian Federation	State Institution of Healthcare Ulyanovsk Regional Clinical Hospital	Ulyanovsk
Russian Federation	GUZ "Novgorod Regional Clinical Hospital"; Cardioreumatological	Veliky Novgorod
Russian Federation	Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"	Voronezh
Russian Federation	Voronezh Regional Clinical Hospital #1	Voronezh
Russian Federation	SHI Yaroslavl Regional Clinical Hospital	Yaroslavl

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	Health Assessment Questionnaire (HAQ) Score	HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.	Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
Primary	Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment	HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.	Weeks 4, 8, 12, 16, 20, and 24
Primary	Change in HAQ Score at Week 24	HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.	Baseline and Week 24
Secondary	Pain Score as Assessed by Visual Analogue Scale (VAS)	Participant's global assessment of pain was assessed using a 100-millimeter (mm) horizontal VAS (0 to 100 mm) with 0=pain absent and 100=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	European Quality of Life - 5 Dimensions (EQ-5D) Score	EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Change in EQ-5D Score at Week 24 From Baseline	EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Minimum clinically significant change in EQ-5D corresponds to the parameter differences before and after treatment = 0.10. Graduations of assessment of the therapy efficacy by EQ-5D are: Difference (?) EQ-5D less than (<)0.10 points: none; 0.10 less than or equal to (=)? EQ-5D =0.24: minimal effect; 0.24= ? EQ-5D <0.31: satisfactory effect; ? EQ-5D greater than or equal to (=)0.31 points: pronounced effect.	Baseline and Week 24
Secondary	General Health Score as Assessed by EQ-5D VAS	Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D	Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality. Positive response was defined as an increase of EQ-5D score by 0.1 or more i.e. it is a clinically significant increase.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Change in General Health Assessed by VAS	Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.	Baseline and Week 24
Secondary	Disease Activity Score Based on 28-Joint Count (DAS28)	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Change in DAS28 Score From Baseline to Week 24		Baseline and Week 24
Secondary	Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment	DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR mm/hour, and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Disease activity: 0=remission (DAS28 less than [<] 2.6), I=low (DAS28 less than or equal to [=]2.6 to <3.2), II=moderate (DAS28=3.2 to 5.1), III=high (DAS28 greater than [>]5.1).	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	ACR20/50/70 response: =20%, =50%, or =70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) and in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase response: C-reactive protein (CRP) or ESR.	Weeks 0, 4, 8, 12, 16, 20, and 24
Secondary	Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	The DAS28-based EULAR response criteria were used to measure individual response as no effect, good effect, and moderate effect, depending on the extent of change from baseline and the level of disease activity reached. Good effect: change from baseline >1.2 with DAS28 score =3.2; moderate effect: change from baseline >1.2 with DAS28 score 3.2 to 5.1 or change from baseline >0.6 to <1.2 with DAS28 score <3.2; no effect: change from baseline =0.6 or change from baseline >0.6 and =1.2 with DAS28 score >5.1.	Weeks 4, 8, 12, 16, 20, and 24
Secondary	C-Reactive Protein	CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.	Weeks 4, 8, 12, 16, 20, and 24
Secondary	Erythrocyte Sedimentation Rate	ESR (mm/hr) is used to determine the acute phase response.	Weeks 4, 8, 12, 16, 20, and 24