Tocilizumab Real-Life Human Factors (RLHFs) Validation Study

Study Overview
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Brief Summary
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This study is designed to evaluate RLHFs concerning administration of the tocilizumab autoinjector AI-1000 G2 in adults with rheumatoid arthritis (RA) who have been receiving subcutaneous (SC) tocilizumab using the commercially available prefilled syringe and needle safety device (PFS-NSD). The study will enroll participants with RA, a subset of whom will be assigned to perform self-injection with the AI-1000 G2. Enrolled caregivers (CGs) and healthcare professionals (HCPs) will administer the AI-1000 G2 injection to the remaining study participants.

Official Title
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Tocilizumab Real-Life Human Factors Validation Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Device: AI-1000 G2
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with RA for greater than or equal to (>/=6) months receiving 162 mg tocilizumab PFS-NSD for >/=8 weeks and who are suitable for continued treatment at their currently prescribed dose CGs and professionally qualified HCPs who are able and willing to administer the injection Exclusion Criteria: RA: Functional status Class IV RA: Neuropathies or other conditions that might interfere with pain evaluation RA: Pregnant or breastfeeding RA: Low neutrophil or platelet count at last laboratory assessment RA: Elevated liver enzymes at last laboratory assessment Current participation in another interventional clinical trial Criteria that might give the participant/CG/HCP an advantage in injection tasks such as employment in the pharmaceutical industry, etc.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caregivers<br>CGs will perform injection of SC tocilizumab to a subset of participants with RA using the AI-1000 G2 device. Visit 1 (Day 0) will be conducted for administration training, while Visits 2 and 3 (Days 14 and 28) will be conducted for use/performance evaluation. | Device: AI-1000 G2<br>* Tocilizumab will be administered using the AI-1000 G2.<br>Drug: Tocilizumab<br>* Participants will receive three doses of SC tocilizumab using the AI-1000 G2 device at Visits 1, 2, and 3 (Days 0, 14, and 28). The dose will remain at 162 milligrams (mg) unless changes are required per protocol for safety or efficacy reasons.<br>* Other names: Actemra/RoActemra, RO4877533;|
| Experimental: Healthcare Professionals<br>HCPs will perform injection of SC tocilizumab to a subset of participants with RA using the AI-1000 G2 device. Because enrolled HCPs are to be professionally qualified to deliver SC injections, no administration training will be provided. Visits 2 and 3 (Days 14 and 28) will be conducted for use/performance evaluation. | Device: AI-1000 G2<br>* Tocilizumab will be administered using the AI-1000 G2.<br>Drug: Tocilizumab<br>* Participants will receive three doses of SC tocilizumab using the AI-1000 G2 device at Visits 1, 2, and 3 (Days 0, 14, and 28). The dose will remain at 162 milligrams (mg) unless changes are required per protocol for safety or efficacy reasons.<br>* Other names: Actemra/RoActemra, RO4877533;|
| Experimental: RA Group 1 (Self-Administration)<br>Participants with RA will perform self-injection of SC tocilizumab with the AI-1000 G2 device. Visit 1 (Day 0) will be conducted for administration training, while Visits 2 and 3 (Days 14 and 28) will be conducted for use/performance evaluation. | Device: AI-1000 G2<br>* Tocilizumab will be administered using the AI-1000 G2.<br>Drug: Tocilizumab<br>* Participants will receive three doses of SC tocilizumab using the AI-1000 G2 device at Visits 1, 2, and 3 (Days 0, 14, and 28). The dose will remain at 162 milligrams (mg) unless changes are required per protocol for safety or efficacy reasons.<br>* Other names: Actemra/RoActemra, RO4877533;|
| Other: RA Group 2 (Administration by CG)<br>CGs will perform injection of SC tocilizumab to participants with RA using the AI-1000 G2 device. Visit 1 (Day 0) will be conducted for administration training, while Visits 2 and 3 (Days 14 and 28) will be conducted for use/performance evaluation. | Device: AI-1000 G2<br>* Tocilizumab will be administered using the AI-1000 G2.<br>Drug: Tocilizumab<br>* Participants will receive three doses of SC tocilizumab using the AI-1000 G2 device at Visits 1, 2, and 3 (Days 0, 14, and 28). The dose will remain at 162 milligrams (mg) unless changes are required per protocol for safety or efficacy reasons.<br>* Other names: Actemra/RoActemra, RO4877533;|
| Other: RA Group 3 (Administration by HCP)<br>HCPs will perform injection of SC tocilizumab to participants with RA using the AI-1000 G2 device. Because enrolled HCPs are to be professionally qualified to deliver SC injections, no administration training will be provided. Visit 1 (Day 0) will be performed by the study nurse. Visits 2 and 3 (Days 14 and 28) will be conducted by the HCP for use/performance evaluation. | Device: AI-1000 G2<br>* Tocilizumab will be administered using the AI-1000 G2.<br>Drug: Tocilizumab<br>* Participants will receive three doses of SC tocilizumab using the AI-1000 G2 device at Visits 1, 2, and 3 (Days 0, 14, and 28). The dose will remain at 162 milligrams (mg) unless changes are required per protocol for safety or efficacy reasons.<br>* Other names: Actemra/RoActemra, RO4877533;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Successfully Performed Safety-Critical and Essential Tasks During First Unassisted Use | Safety-critical tasks included those tasks where errors would have a reasonably foreseeable potential for clinical impact/harm, potentially resulting in direct physical injury to the user and/or conditions that require medical intervention. Safety-critical tasks included the following: release activation button; check the expiry date; inspect device prior to use; and inspect medication prior to use. Essential tasks included those essential to the execution of the injection. Essential tasks included the following: open the carton, remove the device and associated documents; remove cap; start an injection by depressing the needle-shield at the injection site and pressing the activation button; and hold the autoinjector until the complete dose has been delivered. The percentage of participants who successfully performed safety-critical and essential tasks during the first unassisted use (Day 14) was reported. | Day 14 | 
| Percentage of Participants Who Successfully Performed Safety-Critical and Essential Tasks During Second Unassisted Use | Safety-critical tasks included those tasks where errors would have a reasonably foreseeable potential for clinical impact/harm, potentially resulting in direct physical injury to the user and/or conditions that require medical intervention. Safety-critical tasks included the following: release activation button; check the expiry date; inspect device prior to use; and inspect medication prior to use. Essential tasks included those essential to the execution of the injection. Essential tasks included the following: open the carton, remove the device and associated documents; remove cap; start an injection by depressing the needle-shield at the injection site and pressing the activation button; and hold the autoinjector until the complete dose has been delivered. The percentage of participants who successfully performed safety-critical and essential tasks during the second unassisted use (Day 28) was reported. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Successfully Performed Ancillary Tasks During First and Second Unassisted Use | Ancillary tasks included those tasks where the potential harm resulting from use error would be minor in severity, or the resultant harms were estimated to occur at sufficiently low levels. Ancillary tasks included the following: wash hands; clean the injection site with alcohol swab; wait for the alcohol to dry; dispose of the autoinjector cap; inspect full dose delivered after use; dispose of the autoinjector; and treatment of injection site after injection. The percentage of participants who succesffully performed ancillary tasks during the first (Day 14) and second unassisted use (Day 28) was reported. | Days 14, 28 | 
| Visual Analog Scale (VAS) Score for Injection Pain Among Participants With RA | Injection pain was assessed on a continuous 100-millimeter (mm) VAS, where 0 mm represents no pain and 100 mm represents unbearable pain. The mean VAS response at each assessment timepoint was reported among participants with RA. | 0 and 15 minutes after injection on Days 0, 14, 28 | 
| Percentage of Participants by Response to Categorical Scale of Injection Pain Among Participants With RA | Injection pain was assessed on a categorical 6-point Likert scale, ranging from no pain to severe and intolerable. The percentage of participants was reported by response at each assessment timepoint among participants with RA. | 0 and 15 minutes after injection on Days 0, 14, 28 | 
| Percentage of Participants by Response to Device Satisfaction Questionnaire | Device satisfaction was assessed using twelve questions on a categorical 5-point Likert scale, ranging from strongly agree to strongly disagree. Question (Q) 1 (felt the autoinjection was easy to use), Q2 (felt comfortable while using the autoinjector), Q3 (felt the autoinjector was easy to hold), Q4 (able to tell when injection had completed), Q5 (felt he/she can inject properly with the autoinjector), Q6 (felt he/she had control over the injection process), Q7 (felt confident that he/she injected successfully), Q8 (felt it is easy to dispose of the autoinjector), Q9 (autoinjector would help to manage his/her injection schedule), Q10 (liked the look/feel of the autoinjector), Q11 (would recommend the autoinjector to someone else who needed to inject), Q12 (would continue having injections with the autoinjector). The percentage of participants was reported by response at each assessment among participants with RA, CGs, and HCPs. | Days 0, 14, 28 | 
| Tender Joint Count (TJC) Among Participants With RA | Sixty-eight joints were assessed for tenderness among participants with RA. The number of tender joints at Baseline was reported. | Baseline (Day 0) | 
| Swollen Joint Count (SJC) Among Participants With RA | Sixty-six joints were assessed for swelling among participants with RA. The number of swollen joints at Baseline was reported. | Baseline (Day 0) | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Among Participants With RA | Ability to perform daily living activities was assessed across eight component sets including dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common activities. Twenty questions were scored on a 4-point Likert scale from 0 meaning without any difficulty to 3 meaning unable to do. The overall score was computed as the sum of domain scores divided by the number of domains answered. Therefore, the score range for HAQ-DI was the same as that of the individual questions, that is, from 0 to 3, where 0 indicates least difficulty and 3 indicates extreme difficulty. The mean change from baseline in HAQ-DI at each assessment was reported among participants with RA. | Days 0, 14, 28 |