Trial Outcomes & Findings for A Long-Term Safety Extension Study of WA19926 in Participants With Rheumatoid Arthritis (NCT NCT01649804)

Last Updated: 2016-11-04

Results Overview

An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Adverse Events of Special Interest for this study were: Serious and/or medically significant infections; myocardial infarction/Acute coronary syndrome; Gastrointestinal perforation; Malignancies; Anaphylaxis/hypersensitivity reactions; Demyelinating disorders; Stroke and Serious and/or medically significant bleeding and hepatic events.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

12 participants

Primary outcome timeframe

End of Study (Week 104 or early withdrawal)

Results posted on

2016-11-04

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab Tocilizumab (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Overall Study STARTED	12
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Tocilizumab (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Overall Study Administrative/Other	8

Baseline Characteristics

A Long-Term Safety Extension Study of WA19926 in Participants With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=12 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Age, Continuous	51.25 years STANDARD_DEVIATION 8.67 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: End of Study (Week 104 or early withdrawal)

Population: Analysis population included all the enrolled participants in the study.

Outcome measures

Outcome measures
Measure	Tocilizumab n=12 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) AEs	75 percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) SAEs	0 percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) AESI	0 percentage of participants

SECONDARY outcome

Timeframe: Screening and End of Study (Week 104 or early withdrawal)

Population: Analysis population included all the enrolled participants in the study.

The DAS28 (ESR) score is a measure of the participant's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), erythrocyte sedimentation rate (ESR) and general health status. The DAS28-ESR scale ranges from 0 to 10, where higher scores represent higher disease activity. DAS28 \<=3.2 implied low disease activity, DAS \>3.2 to 5.1 implied moderate disease activity, DAS \>5.1 implied high disease activity, and DAS28 \<2.6 = clinical remission.

Outcome measures

Outcome measures
Measure	Tocilizumab n=12 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Remission (Baseline)	5 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity (Baseline)	1 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Moderate Disease Activity (Baseline)	4 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) High Disease Activity (Baseline)	2 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Remission (End of Study)	10 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity (End of Study)	1 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Moderate Disease Activity (End of Study)	0 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) High Disease Activity (End of Study)	1 participants

SECONDARY outcome

Timeframe: Screening and End of Study (Week 104 or early withdrawal)

Population: Analysis population included all the enrolled participants in the study.

The SDAI was defined as the numerical sum of 5 outcome parameters: tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity on a 100 millimeter (mm) Visual analogue scale (VAS) (VAS; 0 = no disease activity and 100 = worst disease activity) and level of C-reactive protein (CRP) (milligram per deciliter \[mg/dl\], normal \< 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=12 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Remission (End of Study)	3 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Low Disease Activity (End of Study)	7 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Moderate Disease Activity (End of Study)	1 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) High Disease Activity (End of Study)	1 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Remission (Baseline)	0 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Low Disease Activity (Baseline)	6 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) Moderate Disease Activity (Baseline)	3 participants
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) High Disease Activity (Baseline)	3 participants

SECONDARY outcome

Timeframe: Week 12 and Week 104

Population: Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.

Tender joint count was performed by a skilled assessor, evaluating 68 joints for tenderness.

Outcome measures

Outcome measures
Measure	Tocilizumab n=11 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Decreased (Week 12; n=11)	5 participants
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Unchanged (Week 12; n=11)	4 participants
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Increased (Week 12;n=11)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Decreased (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Unchanged (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) Increased (Week 104;n=4)	0 participants

SECONDARY outcome

Timeframe: Week 12 and Week 104

Population: Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.

Swollen joint count was performed by a skilled assessor, evaluating 66 joints for swelling.

Outcome measures

Outcome measures
Measure	Tocilizumab n=11 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Decreased (Week 12; n=11)	3 participants
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Unchanged (Week 12; n=11)	7 participants
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Increased (Week 12;n=11)	1 participants
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Decreased (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Unchanged (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) Increased (Week 104;n=4)	0 participants

SECONDARY outcome

Timeframe: End of Study (Week 104 or early withdrawal)

Population: This outcome could not be evaluated as there were no participants who had achieved drug-free remission, per protocol definition.

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 included restarting of the study drug treatment. Time to RA flare was defined as the period of drug-free remission until documentation of RA flare. Drug-free remission was defined as clinical remission (based on DAS28-ESR \< 2.6 and /or SDAI ≤ 3.3) for two consecutive assessment visits, followed by discontinuation of tocilizumab, at the Investigator's discretion, at the second assessment visit.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 12 and Week 104

Population: Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.

The participant global assessment of disease activity was measured using a 100 mm VAS ranging from 0=very good to 100=very bad.

Outcome measures

Outcome measures
Measure	Tocilizumab n=11 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Decreased (Week 12; n=11)	6 participants
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Unchanged (Week 12; n=11)	0 participants
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Increased (Week 12;n=11)	5 participants
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Decreased (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Unchanged (Week 104;n=4)	0 participants
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity Increased (Week 104;n=4)	2 participants

SECONDARY outcome

Timeframe: Week 12 and Week 104

Population: Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.

A participant's overall assessment of pain on a VAS was assessed with a question concerning the amount of pain due to arthritis. Pain was assessed on a 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm).

Outcome measures

Outcome measures
Measure	Tocilizumab n=11 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Decreased (Week 12; n=11)	7 participants
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Unchanged (Week 12; n=11)	4 participants
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Increased (Week 12;n=11)	0 participants
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Decreased (Week 104;n=4)	2 participants
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Unchanged (Week 104;n=4)	0 participants
Number of Participants With Decreased, Unchanged, and Increased Participant Global Assessment of Pain Increased (Week 104;n=4)	2 participants

SECONDARY outcome

Timeframe: End of Study (Week 104 or early withdrawal)

Population: Analysis population included all the enrolled participants in the study.

The Health Assessment Questionnaire Disability Index (HAQ-DI) is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible scores range from 0 to 3, where 0=least difficulty, and 3=extreme difficulty.

Outcome measures

Outcome measures
Measure	Tocilizumab n=12 Participants Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Health Assessment Questionnaire Disability Index (HAQ-DI)	1.18 units on a scale Standard Deviation 0.953

Adverse Events

Tocilizumab

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tocilizumab n=12 participants at risk Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
Gastrointestinal disorders Diarrhoea	16.7% 2/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Gastrointestinal disorders Ranula	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Cystitis	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Influenza	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Nasopharyngitis	25.0% 3/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Otitis externa	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Otitis media	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Infections and infestations Respiratory tract infection	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Injury, poisoning and procedural complications Arthropod bite	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Investigations White blood cell count decreased	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Nervous system disorders Sciatica	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Psychiatric disorders Depression	8.3% 1/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
Skin and subcutaneous tissue disorders Dermatitis	16.7% 2/12 • End of Study (Week 104 or early withdrawal) An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.

Additional Information

Medical Communications

Hoffmann-La Roche

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 only after the first publication or presentation that involves the Overall Study. The 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