Effect of SAR153191 (REGN88) With Methotrexate in Patients With Active Rheumatoid Arthritis Who Failed TNF-α Blockers
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Purpose
Primary Objective:
- Demonstrate that sarilumab (SAR153191/REGN88) on top of methotrexate [MTX] is superior in efficacy to placebo for the relief of signs and symptoms of Rheumatoid Arthritis [RA], in patients with active RA who have failed up to 2 Tumor Necrosis Factor α [TNF-α] antagonists.
Secondary Objectives:
- Assess the safety of sarilumab;
- Document the pharmacokinetic profile of sarilumab.
| Condition | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Drug: Sarilumab Drug: Placebo Drug: Golimumab Drug: methotrexate [MTX] Drug: Folic/folinic acid |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomized, Double-blind, Parallel-group, Placebo- and Active Calibrator-controlled Study Assessing the Clinical Benefit of SAR153191 Subcutaneous (SC) on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis (RA) Who Have Failed Previous TNF-α Antagonists |
- Percentage of participants who achieve 20% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR20] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Percentage of participants who achieve 50% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR50] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Percentage of participants who achieve 70% improvement from baseline according to the American College of Rheumatology core set disease activity index [ACR70] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Disease Activity Score [DAS28] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- European League Against Rheumatism [EULAR] response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Percentage of participants with DAS28 remission (DAS28 < 2.6) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Incidence of Adverse Events [ Time Frame: up to 18 weeks ] [ Designated as safety issue: Yes ]
- Serum concentration of functional and bound sarilumab [ Time Frame: up to 18 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 16 |
| Study Start Date: | November 2010 |
| Study Completion Date: | September 2011 |
| Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Sarilumab 150 mg + MTX
Sarilumab 75 mg/mL, 2 ml once a week for 12 weeks, plus placebo (for golimumab), 0.5 ml every 4 weeks to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week. Folic/folinic acid continued according to local standard. |
Drug: Sarilumab
Pharmaceutical form: solution for injection Route of administration: subcutaneous Other Names:
Drug: Placebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution) Pharmaceutical form: tablet Route of administration: oral |
|
Placebo Comparator: Placebo + MTX
Placebo (for sarilumab), 2 ml once a week for 12 weeks, plus placebo (for golimumab), 0.5 ml every 4 weeks to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week. Folic/folinic acid continued according to local standard. |
Drug: Placebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution) Pharmaceutical form: tablet Route of administration: oral |
|
Active Comparator: Golimumab 50 mg + MTX
Golimumab 50 mg/0.5 ml, 0.5 ml every 4 weeks for 12 weeks, plus placebo (for sarilumab), 2 ml once a week to maintain the blind, in addition to methotrexate [MTX], 15 to 25 mg once a week. Folic/folinic acid continued according to local standard. |
Drug: Placebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous Pharmaceutical form: solution for injection Route of administration: subcutaneous Other Name: Simponi®
Drug: methotrexate [MTX]
Pharmaceutical form: tablet or solution for injection Route of administration: Oral (tablet) or subcutaneous, intramuscular (solution) Pharmaceutical form: tablet Route of administration: oral |
Detailed Description:
The duration of the study period for each participant was approximately 22 weeks; including up to 4 weeks screening period, 12-week double-blind treatment period and 6-week safety follow-up period.
Participants who completed the 12-week treatment period were offered enrollment in a separate long-term extension study (LTS11210/NCT01146652).
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Diagnosis of rheumatoid arthritis ≥6 months duration and American College of Rheumatology [ACR] Class I-III functional status at screening and baseline visits;
-
Active disease defined as:
- At least 6 of 68 tender joints and 6 of 66 swollen joints at screening and baseline visits, and
- hs-C-Reactive Protein [hs-CRP] >10 g/L or Erythrocyte Sedimentation Rate [ESR] >28 mm/hr at screening visit;
- Continuous treatment with Methotrexate for at least 12 weeks and on stable dose (minimum 10 mg/week) for at least 6 weeks prior to the screening visit;
-
Patient considered as Primary TNF-α blocker nonresponder. i.e.:
- Appropriate for previous TNF-α blocker therapy
- Lack of adequate clinical response after at least 3 months TNF-α blocker therapy (up to 2 agents) with Methotrexate or other synthetic disease modifying anti-rheumatic drug [DMARD] co-therapy.
Exclusion criteria:
- Age <18 years or >75 years;
- Pregnant or breastfeeding woman or woman of childbearing potential, unwilling to utilize adequate contraception or not to become pregnant during the entire study;
- Fever (>38°C), or chronic, persistent, or recurring infection(s);
- History of demyelinating disease;
- Current underlying hepatobiliary disease.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01217814
| United States, New Jersey | |
| Investigational Site Number 840026 | |
| Freehold, New Jersey, United States, 07728 | |
| United States, New York | |
| Investigational Site Number 840043 | |
| New York, New York, United States, 11201 | |
| United States, Tennessee | |
| Investigational Site Number 840025 | |
| Jackson, Tennessee, United States, 38305 | |
| United States, Texas | |
| Investigational Site Number 840038 | |
| Austin, Texas, United States, 78705 | |
| Colombia | |
| Investigational Site Number 170004 | |
| Barranquilla, Colombia | |
| Investigational Site Number 170005 | |
| Barranquilla, Colombia | |
| Investigational Site Number 170007 | |
| Bucaramanga, Colombia | |
| Czech Republic | |
| Investigational Site Number 203002 | |
| Uherske Hradiste, Czech Republic, 68601 | |
| Italy | |
| Investigational Site Number 380002 | |
| Firenze, Italy, 50141 | |
| Investigational Site Number 380005 | |
| Genova, Italy, 16132 | |
| Mexico | |
| Investigational Site Number 484008 | |
| Durango, Mexico, 34270 | |
| Investigational Site Number 484002 | |
| Guadalajara, Mexico, 44690 | |
| Spain | |
| Investigational Site Number 724004 | |
| Oviedo, Spain, 33006 | |
| Investigational Site Number 724002 | |
| Valencia, Spain, 46009 | |
| Study Director: | Clinical Sciences & Operations | Sanofi |
More Information
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT01217814 History of Changes |
| Other Study ID Numbers: | ACT11575 2010-021020-94 U1111-1115-3763 |
| Study First Received: | October 7, 2010 |
| Last Updated: | November 9, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Methotrexate Antibodies, Monoclonal Leucovorin Levoleucovorin Folic Acid 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 Antidotes Protective Agents |
ClinicalTrials.gov processed this record on September 23, 2016