Trial Outcomes & Findings for A Study to Assess the Effect of Tocilizumab on Signs and Symptoms in Patients With Rheumatoid Arthritis (NCT NCT00848120)

Last Updated: 2017-08-03

Results Overview

ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

29 participants

Primary outcome timeframe

Week 24

Results posted on

2017-08-03

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab 8 Milligrams Per Kilogram (mg/kg) Participants received tocilizumab 8 mg/kg intravenously (IV) once every 4 weeks for 24 weeks.
Overall Study STARTED	29
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab 8 Milligrams Per Kilogram (mg/kg) Participants received tocilizumab 8 mg/kg intravenously (IV) once every 4 weeks for 24 weeks.
Overall Study Adverse Event	1

Baseline Characteristics

A Study to Assess the Effect of Tocilizumab on Signs and Symptoms in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Age, Continuous	47 years STANDARD_DEVIATION 14.1 • n=99 Participants
Sex: Female, Male Female	28 Participants n=99 Participants
Sex: Female, Male Male	1 Participants n=99 Participants

PRIMARY outcome

Timeframe: Week 24

Population: ITT population

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20 Response) at Week 24	86 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population

ACR50 response: ≥50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (VAS), 4) participant assessment of functional disability via a HAQ, and 5) ESR at each visit.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) at Week 24	66 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population

ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (VAS), 4) participant assessment of functional disability via a HAQ, and 5) ESR at each visit.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) at Week 24	48 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To calculate HAQ-DI the participant must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst).

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
HAQ Disability Index (HAQ-DI) Score at Baseline and Week 24 Week 24	0.23 units on a scale Standard Deviation 0.31
HAQ Disability Index (HAQ-DI) Score at Baseline and Week 24 Baseline	0.75 units on a scale Standard Deviation 0.53

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the 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 participants 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 the health status.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline and Week 24 Baseline	1.93 units on a scale Standard Deviation 0.61
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline and Week 24 Week 24	1.03 units on a scale Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

DAS28-ESR calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (millimeters per hour \[mm/hour\]) and Patient's Global Assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Disease Activity Score Based on 28 Joint Count - Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline and Week 24 Baseline	6.94 units on a scale Standard Deviation 0.53
Disease Activity Score Based on 28 Joint Count - Erythrocyte Sedimentation Rate (DAS28-ESR) at Baseline and Week 24 Week 24	2.73 units on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population

DAS28-ESR calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hour) and Patient's Global Assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 \<2.6=remission.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Percentage of Participants With Disease Remission at Week 24 Assessed Using DAS28-ESR	34 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Percentage of Participants With Low Disease Activity at Week 24 Assessed Using DAS28-ESR	45 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, and 24

Population: ITT Population

Time to onset of ACR 20/50/70 response was calculated as the number of weeks from the administration of the first dose of study drug until the date of first achievement of ACR 20/50/70 per criteria.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg n=29 Participants Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Time to Onset of ACR20/50/70 Response ACR20	4 weeks Interval 4.0 to 8.0
Time to Onset of ACR20/50/70 Response ACR50	12 weeks Interval 8.0 to 24.0
Time to Onset of ACR20/50/70 Response ACR70	24 weeks Interval 16.0 to The 3rd quartile range could not be estimated because less than 75% of participants achieved ACR70.

Adverse Events

Tocilizumab 8 mg/kg

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab 8 mg/kg n=29 participants at risk Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Pregnancy, puerperium and perinatal conditions Pregnancy	3.4% 1/29 • Number of events 1 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.

Other adverse events

Other adverse events
Measure	Tocilizumab 8 mg/kg n=29 participants at risk Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 24 weeks.
Metabolism and nutrition disorders Elevated AST/SGOT level	82.8% 24/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Metabolism and nutrition disorders Elevated ALT/SGPT level	69.0% 20/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Metabolism and nutrition disorders Elevated AST ad ALT levels	10.3% 3/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Infections and infestations Urinary tract infection (UTI)	10.3% 3/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Infections and infestations Upper respiratory tract infection	6.9% 2/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Infections and infestations Ear infection	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Infections and infestations Systemic viral infection	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Metabolism and nutrition disorders Hypercholesterolemia	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Hepatobiliary disorders Fatty liver	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Gastrointestinal disorders Abdominal pain	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Gastrointestinal disorders Colonic diverticulitis	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Gastrointestinal disorders Internal hemorrhoids, grade 1	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Gastrointestinal disorders Non ulcer dyspepsia	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Pruritic back	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Pruritic, erythematous scaly plaques over interdigital areas (right foot, first-third toes)	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Rashes on chest: back	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Rashes on toes	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Erythematous, pruritic maculopapular rash	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Skin and subcutaneous tissue disorders Contact dermatitis	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Nervous system disorders Carpal tunnel syndrome (R)	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Musculoskeletal and connective tissue disorders Trigger finger 4th digit left hand	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine myoma with nabothian cysts	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Nervous system disorders Headache	6.9% 2/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Nervous system disorders Paresthesia at the palm of infusion	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Musculoskeletal and connective tissue disorders Knee effusion	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
General disorders Chills and increased pain	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
General disorders Headache/back pain	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
General disorders Fever and headache	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Respiratory, thoracic and mediastinal disorders Cough productive due to infection	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Respiratory, thoracic and mediastinal disorders Acute pharyngitis probably viral etiology	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Respiratory, thoracic and mediastinal disorders Sore throat	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Infections and infestations Dengue	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.
Ear and labyrinth disorders Folliculitis left ear	3.4% 1/29 • Adverse events were recorded from the date of screening until 4 weeks after the last infusion.

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER