NCT00773461

A Study of Tocilizumab in Combination With DMARD Therapy in Patients With Active Rheumatoid Arthritis.

Completed Phase 3 Results posted Last updated 1 August 2017

What this trial tests

Phase 3 trial testing tocilizumab [RoActemra/Actemra] in Rheumatoid Arthritis in 209 participants. Completed in 22 July 2010.

Timeline

31 October 2008

Primary endpoint
22 July 2010

22 July 2010

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	209
Start date	31 October 2008
Primary completion	22 July 2010
Estimated completion	22 July 2010
Sites	9 locations across China

Drugs / interventions tested

• tocilizumab [RoActemra/Actemra] — full drug profile →
• Placebo

Conditions studied

• Rheumatoid Arthritis — all drugs for Rheumatoid Arthritis →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 70, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 Primary · Week 24

To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was car

ITT Population

Group	Value	95% CI
Placebo + DMARDs	24.6
Tocilizumab + DMARDs	69.8

ITT Population (Sensitivity)

Group	Value	95% CI
Placebo + DMARDs	24.6
Tocilizumab + DMARDs	73.4

Percentage of Participants With ACR50 and ACR70 Responses at Week 24 Secondary · Week 24

To achieve an ACR50 or ACR 70 response required at least a 50% or 70% improvement, compared with baseline in both TJC and SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, HAQ-DI and CRP. CRP was used primarily for the calculation of the ACR response; if missing, ESR was substituted.

ACR 50

Group	Value	95% CI
Placebo + DMARDs	10.1
Tocilizumab + DMARDs	38.8

ACR 70

Group	Value	95% CI
Placebo + DMARDs	2.9
Tocilizumab + DMARDs	12.9

Number of Participants Who Received Escape Therapy Secondary · 24 Weeks

Participants who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 could, if requested and deemed necessary by the investigator, receive escape therapy, comprising adjustment of the background DMARD dose and/or treatment with a different traditional DMARD.

Group	Value	95% CI
Placebo + DMARDs	4
Tocilizumab + DMARDs	0

Change in Tender and Swollen Joint Counts From Baseline to Week 24 Secondary · Baseline and Week 24

68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. 66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

Swollen Joint Count

Group	Value	95% CI
Placebo + DMARDs	-4.5	± 11.61
Tocilizumab + DMARDs	-9.9	± 9.26

Tender Joint Count

Group	Value	95% CI
Placebo + DMARDs	-6.2	± 12.31
Tocilizumab + DMARDs	-16.5	± 12.06

Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24 Secondary · Baseline and Week 24

The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Group	Value	95% CI
Placebo + DMARDs	-8.7	± 26.27
Tocilizumab + DMARDs	-26.4	± 24.69

Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24 Secondary · Baseline and Week 24

The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

Group	Value	95% CI
Placebo + DMARDs	-9.9	± 22.61
Tocilizumab + DMARDs	-29.1	± 22.43

Change in Participant's Global Assessment of Pain From Baseline to Week 24 Secondary · Baseline and Week 24

The participants assessed their pain on a 0 to 100 mm VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

Group	Value	95% CI
Placebo + DMARDs	-5.9	± 23.97
Tocilizumab + DMARDs	-23.5	± 25.78

Change in C-Reactive Protein From Baseline to Week 24 Secondary · Baseline and Week 24

The serum concentration of CRP an acute phase inflammatory marker, is measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

Group	Value	95% CI
Placebo + DMARDs	-0.083	± 2.310
Tocilizumab + DMARDs	-1.865	± 2.152

Change in ESR From Baseline to Week 24 Secondary · Baseline and Week 24

The ESR was measured in mm/hour. A reduction in the level is considered an improvement.

Group	Value	95% CI
Placebo + DMARDs	-4.4	± 22.46
Tocilizumab + DMARDs	-42.7	± 26.23

Percentage of Participants With Low Disease Activity and in Clinical Remission Secondary · Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, ESR 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. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Baseline Low Disease Activity (n= 69,139)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	0

Baseline Remission (n=69, 139)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	0

Baseline Remission first achieved (n=69, 139)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	0

Week 2 Low Disease Activity (n= 67,138)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	2.2

Week 2 Remission (n= 67,138)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	0.7

Week 2 Remission first achieved (n= 67,138)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	0.7

Week 4 Low Disease Activity (n= 67,139)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	12.9

Week 4 Remission (n=67,139)

Group	Value	95% CI
Placebo+DMARD	0
Tocilizumab + DMARDs	5.0

Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Secondary · Baseline and Week 24

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in health status.

Group	Value	95% CI
Placebo + DMARDs	2.08	± 7.684
Tocilizumab + DMARDs	6.51	± 9.244

Mean Rheumatoid Factor at Baseline and Week 24 Secondary · Baseline and 24 Weeks

Rheumatoid factor (RF) is a disease characteristic and more than 85% of the participants studied were positive for the factor. These data are from patients who were RF positive. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL.

Baseline, n = 61, 125

Group	Value	95% CI
Placebo + DMARDs	179.5	± 199.57
Tocilizumab + DMARDs	262.2	± 360.39

Week 24, n = 57, 118

Group	Value	95% CI
Placebo + DMARDs	198.6	± 277.06
Tocilizumab + DMARDs	204.6	± 365.25

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were monitored and recorded throughout the study.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo + DMARDs

Serious: 4/68 (6%)

Deaths: —

Tocilizumab + DMARDs

Serious: 1/139 (1%)

Deaths: —

Serious adverse events (5 terms)

Reaction	System	Placebo + DMARDs	Tocilizumab + DMARDs
Abscess Limb	Infections and infestations	—	—
Herpes Zoster	Infections and infestations	—	—
Uterine Infection	Infections and infestations	—	—
Pyrexia	General disorders	—	—
Neutrophil Count Decreased	Investigations	—	—

Other adverse events (55 terms — click to expand)

Reaction	System	Placebo + DMARDs	Tocilizumab + DMARDs
Upper respiratory tract infection	Infections and infestations	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Nasopharyngitis	Infections and infestations	—	—
White blood cell count decreased	Investigations	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Influenza	Infections and infestations	—	—
Neutrophil count decreased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Aphthous stomatitis	Gastrointestinal disorders	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—
Vision blurred	Eye disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Pyrexia	General disorders	—	—
Dizziness	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Abscess limb	Infections and infestations	—	—
Cystitis	Infections and infestations	—	—
Helicobacter infection	Infections and infestations	—	—
Herpes zoster	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Pharyngitis	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Uterine infection	Infections and infestations	—	—
Transaminases increased	Investigations	—	—
Blood bilirubin unconjugated increased	Investigations	—	—
Blood creatinine increased	Investigations	—	—
Hepatic enzyme increased	Investigations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Cheilitis	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Gingival ulceration	Gastrointestinal disorders	—	—
Mouth ulceration	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Toothache	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—

Most-reported serious reactions: Abscess Limb, Herpes Zoster, Uterine Infection, Pyrexia, Neutrophil Count Decreased.

Data from ClinicalTrials.gov NCT00773461 adverse events section.

Sponsor's own description

This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Mudano AS, Tanjong Ghogomu E, et al · · 2017 · cited 44× · PMID 28481462 · DOI 10.1002/14651858.cd012657
2. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, et al · · 2017 · cited 38× · PMID 28282491 · DOI 10.1002/14651858.cd012591