To Evaluate The Safety of SAR153191 (REGN88) and Tocilizumab Added to Other RA Drugs in Patients With RA Who Are Not Responding to or Intolerant of Anti-TNF Therapy (SARIL-RA-ASCERTAIN)
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| ClinicalTrials.gov Identifier: NCT01768572 |
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Recruitment Status :
Completed
First Posted : January 15, 2013
Results First Posted : June 26, 2017
Last Update Posted : June 26, 2017
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Primary Objective:
To assess, in the same study, the safety of sarilumab and tocilizumab in participants with rheumatoid arthritis (RA) who were inadequate responders to or intolerant of tumor necrosis factor (TNF) antagonists.
| Condition or disease | Intervention/treatment | Phase |
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| Rheumatoid Arthritis | Drug: sarilumab SAR153191 (REGN88) Drug: tocilizumab Drug: hydroxychloroquine Drug: methotrexate Drug: sulfasalazine Drug: leflunomide Drug: subcutaneous placebo Drug: intravenous placebo | Phase 3 |
Total study duration was up to 34 weeks: Screening up to 28 days, treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks.
After completion of the treatment phase of this study, participants were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 202 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists |
| Study Start Date : | March 2013 |
| Actual Primary Completion Date : | October 2014 |
| Actual Study Completion Date : | October 2014 |
| Arm | Intervention/treatment |
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Experimental: Sarilumab 150 mg q2w
Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (q2w) and placebo intravenous (IV) infusion once every 4 weeks (q4w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD), hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.
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Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form: solution Route of administration: subcutaneous Drug: hydroxychloroquine Dispensed according to local practice. Drug: methotrexate Dispensed according to local practice. Drug: sulfasalazine Dispensed according to local practice. Drug: leflunomide Dispensed according to local practice. Drug: intravenous placebo Pharmaceutical form: solution Route of administration: intravenous |
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Experimental: Sarilumab 200 mg q2w
Sarilumab 200 mg SC injection q2w and placebo IV infusion q4w was added to one or a combination of the nonbiologic DMARD, hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.
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Drug: sarilumab SAR153191 (REGN88)
Pharmaceutical form: solution Route of administration: subcutaneous Drug: hydroxychloroquine Dispensed according to local practice. Drug: methotrexate Dispensed according to local practice. Drug: sulfasalazine Dispensed according to local practice. Drug: leflunomide Dispensed according to local practice. Drug: intravenous placebo Pharmaceutical form: solution Route of administration: intravenous |
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Active Comparator: Tocilizumab q4w
Tocilizumab 4 mg/kg or 8 mg/kg IV infusion q4w and placebo SC injection q2w was added to one or a combination of the nonbiologic DMARD, hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.
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Drug: tocilizumab
Pharmaceutical form: solution Route of administration: intravenous Drug: hydroxychloroquine Dispensed according to local practice. Drug: methotrexate Dispensed according to local practice. Drug: sulfasalazine Dispensed according to local practice. Drug: leflunomide Dispensed according to local practice. Drug: subcutaneous placebo Pharmaceutical form: solution Route of administration: subcutaneous |
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 211 days ]Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment. All adverse events that occurred from the first dose of the study drug administration up to 60 days after the end of treatment visit were considered as TEAEs. Serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. A summary of SAEs, all other non-serious AEs, regardless of causality, are reported in AE section.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
Diagnosis of RA was, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ≥ 3 months disease duration
ACR Class I-III functional status, was based on the 1991 revised criteria. Moderate-to-severely active RA. Anti-TNF therapy failures, was defined as participants with an inadequate clinical response was defined by the investigator, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 TNF-antagonist, resulting in or requiring their discontinuation. TNF-antagonists were include, but were not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab pegol
Continuous treatment with one or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) for at least 12 consecutive weeks prior to screening and on a stable dose(s) for at least 6 consecutive weeks prior to screening:
- Methotrexate - 10 to 25 milligram/week orally or parenteral (or per local labelling requirements if the dose range differs)
- Leflunomide - 10 to 20 mg orally daily
- Sulfasalazine (SSZ) - 1000 to 3000 mg orally daily
- Hydroxychloroquine (HCQ) - 200 to 400 mg orally daily
Exclusion criteria:
Participants <18 years of age. Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening
Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks prior to screening
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 systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome
Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the Screening Visit, whichever was longer
Participants with active tuberculosis or latent tuberculosis infection. Prior or current history of interstitial lung disease. Prior treatment with anti-interleukin (IL) -6 or anti-IL-6R therapies, including but not limited to tocilizumab or sarilumab
Treatment with anti-TNF agents, as follows:
- Etanercept: within 28 days prior to randomization
- Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to randomization
Treatment with RA-directed biologic agents with non- TNF-α antagonist mechanisms without adequate washout as follows:
- Anakinra: within 28 days prior to randomization
- Abatacept: within 42 days prior to randomization
- Rituximab or other cell depleting agent: Within 6 months prior to randomization or until total lymphocyte count and CD 19+ lymphocyte count were normalized, or whichever was longer
Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib). Participants with a history of invasive opportunistic infection. Prior or current history of malignancy, including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization (baseline) visit
Prior or current history of other significant concomitant illness(es) that, according to Investigator's judgement, was adversely affect the participant's participation in the study.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01768572
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| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT01768572 |
| Other Study ID Numbers: |
SFY13370 2012-003536-23 U1111-1133-7839 ( Other Identifier: UTN ) |
| First Posted: | January 15, 2013 Key Record Dates |
| Results First Posted: | June 26, 2017 |
| Last Update Posted: | June 26, 2017 |
| Last Verified: | June 2017 |
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Hydroxychloroquine Sulfasalazine Methotrexate Leflunomide Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents |
Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Antimalarials Antiprotozoal Agents Antiparasitic Agents |