RA
Conditions
Brief summary
Primary Objective: To collect real-use data of the sarilumab auto-injector device (AID) used by rheumatoid arthritis (RA) participants. Secondary Objective: To compare the pharmacokinetic (PK) exposure of sarilumab administered by AID versus prefilled syringes (PFS).
Detailed description
Total study duration up to 74 weeks: screening up to 4 weeks, AID assessment phase of 12 weeks, extension phase of 52 weeks and post-treatment follow-up of 6 weeks. For participants not entering the extension phase, total study duration up to 22 weeks (screening, AID assessment phase and follow-up).
Interventions
DRUGSarilumab
Pharmaceutical form: Solution Route of administration: Subcutaneous
DEVICEAuto-Injector Device (AID)
DEVICEPre-filled Syringe (PFS)
DRUGMethotrexate
Dispensed according to local practice.
DRUGSulfasalazine
Dispensed according to local practice.
DRUGLeflunomide
Dispensed according to local practice.
DRUGHydroxychloroquine
Dispensed according to local practice.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RA, ≥3 months disease duration; * Participant willing and able to self-inject; * Continuous treatment with 1 or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) (except leflunomide in combination with methotrexate); * Moderate-to-severely active RA.
Exclusion criteria
* Participants \<18 years; * Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonists; * Treatment with tumor necrosis factor (TNF) antagonists; * Treatment with RA-directed biologic agents other than with a TNF-α antagonist mechanism as follows: Anakinra, Abatacept, Rituximab or other cell-depleting agent; * Prior treatment with a Janus kinase inhibitor. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Validated AID Associated Product Technical Failures (PTFs) | Baseline up to Week 12 | A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each participant was given a diary having questions related to participant's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Participants were asked to answer the questions each time they self-inject the sarilumab. If the response was no to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85 | AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). |
Countries
Chile, Mexico, Poland, Russia, South Africa, United States
Participant flow
Recruitment details
The study was conducted at 53 centers in 6 countries. A total of 419 participants were screened between 18 March 2014 and 14 October 2014, out of which 217 participants were enrolled and treated.
Pre-assignment details
Participants were randomized in 1:1:1:1 ratio to Sarilumab 150 mg administered by auto-injector device (AID) or prefilled syringe (PFS) or Sarilumab 200 mg administered by AID or PFS. Participants who completed 12-week AID assessment phase, were treated in open-label extension phase for 52 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks. | 56 |
| Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks. | 53 |
| Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks. | 52 |
| Sarilumab 200 mg by PFS (AID Assessment Phase) Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks. | 56 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| AID Assessment Phase | Adverse Event | 3 | 2 | 6 | 1 | 0 |
| AID Assessment Phase | Other than specified above | 1 | 1 | 1 | 1 | 0 |
| Extension Phase | Adverse Event | 0 | 0 | 0 | 0 | 15 |
| Extension Phase | Entered in this period but not treated | 0 | 0 | 0 | 0 | 4 |
| Extension Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 10 |
| Extension Phase | Other than specified above | 0 | 0 | 0 | 0 | 7 |
Baseline characteristics
| Characteristic | Sarilumab 150 mg by AID (AID Assessment Phase) | Sarilumab 150 mg by PFS (AID Assessment Phase) | Sarilumab 200 mg by AID (AID Assessment Phase) | Sarilumab 200 mg by PFS (AID Assessment Phase) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 13.8 | 54.2 years STANDARD_DEVIATION 14.2 | 55.9 years STANDARD_DEVIATION 12.3 | 50.3 years STANDARD_DEVIATION 12.8 | 53.5 years STANDARD_DEVIATION 13.4 |
| Sex: Female, Male Female | 45 Participants | 43 Participants | 44 Participants | 49 Participants | 181 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 8 Participants | 7 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 56 | 21 / 53 | 24 / 52 | 23 / 56 | 83 / 188 |
| serious Total, serious adverse events | 1 / 56 | 0 / 53 | 3 / 52 | 4 / 56 | 19 / 188 |
Outcome results
Primary
Number of Validated AID Associated Product Technical Failures (PTFs)
A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each participant was given a diary having questions related to participant's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Participants were asked to answer the questions each time they self-inject the sarilumab. If the response was no to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF.
Time frame: Baseline up to Week 12
Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least 1 dose of investigational medicinal product (IMP) with AID and attended at least 1 post-baseline visit during AID assessment phase of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sarilumab 150 mg by AID (AID Assessment Phase) | Number of Validated AID Associated Product Technical Failures (PTFs) | 0 PTFs |
| Sarilumab 200 mg by AID (AID Assessment Phase) | Number of Validated AID Associated Product Technical Failures (PTFs) | 0 PTFs |
Secondary
Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab
AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85
Population: Pharmacokinetic(PK) population included all randomized participants who received at least 1 dose of IMP and have least 1 PK parameter calculated using non compartmental methods following the first (Day 1) or sixth administration (Day 71). Here, Number Analyzed = participants with available data for specified category for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sarilumab 150 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 0-2 | 131 mg*day/L | Standard Deviation 54.5 |
| Sarilumab 150 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 10-12 | 205 mg*day/L | Standard Deviation 126 |
| Sarilumab 200 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 10-12 | 220 mg*day/L | Standard Deviation 130 |
| Sarilumab 200 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 0-2 | 152 mg*day/L | Standard Deviation 76.7 |
| Sarilumab 200 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 0-2 | 235 mg*day/L | Standard Deviation 117 |
| Sarilumab 200 mg by AID (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 10-12 | 455 mg*day/L | Standard Deviation 294 |
| Sarilumab 200 mg by PFS (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 0-2 | 227 mg*day/L | Standard Deviation 94.9 |
| Sarilumab 200 mg by PFS (AID Assessment Phase) | Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab | Week 10-12 | 405 mg*day/L | Standard Deviation 244 |