Rheumatoid Arthritis
Conditions
Brief summary
Primary Objective: To evaluate the immunogenicity of sarilumab administered as monotherapy. Secondary Objectives: * To evaluate the other safety aspects of sarilumab administered as monotherapy. * To assess the exposure of sarilumab administered as monotherapy.
Detailed description
Total study duration was up to 34 weeks: Up to 4-week screening period, 24-week open-label treatment phase, 6-week post-treatment observation. After completion of the treatment phase of this study, participants were eligible to enter a long term safety study (LTS11210 - SARIL-RA-EXTEND) for continuous treatment with sarilumab (SAR153191 \[REGN88\]).
Interventions
Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous
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 rheumatoid arthritis (RA) ≥ 3 months. * Moderately to severely active rheumatoid arthritis. * Participants who per investigator judgment were incomplete responders to at least 12 weeks of an adequate dose of continuous treatment with or who were intolerant of one or a combination of non-biologic disease modifying anti-rheumatic drugs (DMARDs).
Exclusion criteria
* Participants \< 18 years of age. * Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA. * History of juvenile idiopathic arthritis or arthritis onset prior to age 16. * Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome. * Prior treatment with any biologic anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies. * Treatment with prednisone \> 10 mg or equivalent per day, or change in dosage within 4 weeks prior to randomization. * New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors within 4 weeks prior to randomization, except for the use of low-dose acetylsalicylic acid for cardiovascular diseases. * Use of parenteral glucocorticoids or intra-articular glucocorticoids injection within 4 weeks prior to randomization. * Prior treatment with a Janus kinase (JAK) inhibitor (tofacitinib). * New treatment or dose-adjustment to on-going medication for dyslipidemia, such as statin, within 6 weeks prior to randomization. * Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first dose of study drug administration, whichever is longer. * Participants with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, non-metastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization visit. Non-malignant lymphoproliferative disorders are also excluded. * Participants with active tuberculosis or untreated latent tuberculosis infection. * Pregnant or breast feeding women. The above information is not intended to contain all considerations relevant to a Participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | From Baseline to Week 30 [End of study (EOS)] | ADA to sarilumab and anti-sarilumab neutralizing antibodies in serum samples were determined using a validated electrochemiluminescence immunoassay method. Percentage of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from first dose of investigational medicinal product \[IMP\] to last dose of IMP + 60 days) was determined. Persistent ADA Response: treatment-emergent ADA detected at 2 or more consecutive sampling time points during the TEAE period, where the first and last ADA positive samples were separated by a period of at least 16 weeks or if the last measured sample was positive. ADA samples were collected prior to IMP administration at Week 0 (baseline), Week 2, 4, 12, 24 and 30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Sarilumab Concentration | Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30 | Trough Concentration (Ctrough). |
Countries
Chile, Czechia, Estonia, Hungary, Poland, Russia, United States
Participant flow
Recruitment details
The study was conducted at 27 centers in 7 countries. A total of 201 participants were screened between 03 June 2014 and 20 October 2014.
Pre-assignment details
Of 201 participants, 69 participants were screen failures due to exclusion criteria met and inclusion criteria not met. 132 participants were randomized in 1:1 ratio to either sarilumab 150 mg every two weeks (q2w) or sarilumab 200 mg q2w.
Participants by arm
| Arm | Count |
|---|---|
| Sarilumab 150 mg q2w Sarilumab 150 mg SC injection q2w for 24 weeks. | 65 |
| Sarilumab 200 mg q2w Sarilumab 200 mg SC injection q2w for 24 weeks. | 67 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Other than specified above | 0 | 2 |
Baseline characteristics
| Characteristic | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w | Total |
|---|---|---|---|
| Age, Continuous | 51.1 years STANDARD_DEVIATION 12.7 | 53.6 years STANDARD_DEVIATION 14.1 | 52.4 years STANDARD_DEVIATION 13.4 |
| Sex: Female, Male Female | 49 Participants | 57 Participants | 106 Participants |
| Sex: Female, Male Male | 16 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 65 | 23 / 67 |
| serious Total, serious adverse events | 1 / 65 | 2 / 67 |
Outcome results
Primary
Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
ADA to sarilumab and anti-sarilumab neutralizing antibodies in serum samples were determined using a validated electrochemiluminescence immunoassay method. Percentage of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from first dose of investigational medicinal product \[IMP\] to last dose of IMP + 60 days) was determined. Persistent ADA Response: treatment-emergent ADA detected at 2 or more consecutive sampling time points during the TEAE period, where the first and last ADA positive samples were separated by a period of at least 16 weeks or if the last measured sample was positive. ADA samples were collected prior to IMP administration at Week 0 (baseline), Week 2, 4, 12, 24 and 30.
Time frame: From Baseline to Week 30 [End of study (EOS)]
Population: Analysis was performed on immunogenicity population included all randomized participants who received at least one dose of sarilumab with at least one post-dose, evaluable ADA sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sarilumab 150 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Overall positive | 24.6 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Persistent positive | 12.3 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Persistent neutralizing positive | 10.8 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Overall positive | 18.2 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Persistent positive | 6.1 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | Persistent neutralizing positive | 3.0 Percentage of participants |
Secondary
Serum Sarilumab Concentration
Trough Concentration (Ctrough).
Time frame: Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30
Population: Analysis was performed on pharmacokinetic (PK) population consisted of all randomized population actually received at least one or partial dose of IMP, with at least one post-dose, non-missing serum sarilumab concentration. Number of participants analyzed=participants with serum sarilumab concentration assessment at specified time-points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sarilumab 150 mg q2w | Serum Sarilumab Concentration | 7350 ng/mL | Standard Deviation 8030 |
| Sarilumab 200 mg q2w | Serum Sarilumab Concentration | 17200 ng/mL | Standard Deviation 15900 |