A Randomized Open Label, Phase 1b/2 Study to Evaluate Intravenous Administration With Long Dosing Interval Regimens of Sarilumab in Adult Participants With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 140
- 试验地点
- 4
- 主要终点
- Part A: Assessment of Pharmacokinetic (PK) parameters of sarilumab in serum: area under the concentration-time curve [AUClast] for IV doses
研究概览
简要总结
This is a Phase 1/Phase 2 study with:
- 5-arms design for Part A;
- and a single arm for Part B.
The purpose of this study is to measure PK parameters and safety with sarilumab intravenous (IV) with or without concomitant oral conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) in male and female participants with moderately to severely active rheumatoid arthritis aged 18 years of age or older.
Study details include:
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The study duration will be up to 64 weeks.
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The treatment duration will be up to 6 months for each study phase.
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Part A has 10 visits, including a post-treatment end of study (EOS) follow-up visit.
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For participants entering the open label extension to receive the approved 200 mg sarilumab every two weeks (Q2W) dose, there will be 3 additional study visits.
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For the intra-study sarilumab 200 mg Q2W subcutaneous (SC) arm, participants will be evaluated over the course of 24 weeks plus post-treatment EOS follow-up visit following the schedule of activities (SoA) of Part A from Day -1 to Day 29 (total of 8 visits) and the SoA of Part B from Week 4 to Week 24 (total of 8 visits) and a post-treatment end of study (EOS) follow-up visit at Week 30 (Part B) for a total of 17 visits, including a post-treatment EOS follow-up visit.
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Part B has 13 visits, including a post-treatment EOS follow-up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 18 years old or the legal age of consent in the jurisdiction in which the study is taking place or older, at the time of signing the informed consent.
- •Diagnosis of RA, according to the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2010 RA Classification Criteria with ≥3 months disease duration.
- •ACR Class I to III functional status, based on the 1991 revised criteria
- •Moderate-to-severely active RA, defined as: DAS28-ESR>3.
- •Inability to continue treatment with a RA DMARD approved for first line use because of intolerance or inadequate response.
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Any prior (within the defined periods below) or concurrent use of immunosuppressive:
- •Janus kinase (JAK) inhibitor (eg, tofacitinib) within 4 weeks of baseline.
- •Cell-depletion agents (eg, anti CD20) without evidence of recovery of B cells to baseline level.
- •Anakinra within 1 week of baseline.
- •Abatacept within 8 weeks of baseline.
- •Tumor necrosis factor (TNF) inhibitors within 2 to 8 weeks.
- •Alkylating agents including cyclophosphamide (CYC) within 6 months of baseline.
- •Cyclosporine (CsA), azathioprine (AZA) or mycophenolate mofetil (MMF) or leflunomide within 4 weeks of baseline.
- •Therapeutic failure, including inadequate response or intolerance, or contraindication, to biological IL-6 antagonist (prior IL-6 antagonist treatment that was terminated for reasons unrelated to therapeutic failure at least 3 months before baseline is not exclusionary).
- •Unstable methotrexate (MTX) dose (if participant is on concomitant MTX).
- •Concurrent use of systemic corticosteroids (CS) of more than 10 mg/day.
- •Pregnant or breastfeeding woman.
- •Exclusion related to tuberculosis (TB): active TB or a history of incompletely treated TB regardless of screening Quantiferon® result.
- •History of invasive opportunistic infections, including but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, aspergillosis despite resolution or John Cunningham virus (progressive multifocal leukoencephalopathy).
- •Uncontrolled diabetes mellitus.
- •History of prior articular or prosthetic joint infection.
- •Prior or current history of malignancy, including lymphoproliferative diseases, 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 baseline visit.
- •History of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation.
- •History of juvenile idiopathic arthritis or arthritis onset prior to age
- •Severe systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Sarilumab Dose Level 4 (DL4) IV - Part A
Participants will receive Sarilumab DL4 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 IV (Drug)
Sarilumab Dose Level 1 (DL1) IV - Part A
Participants will receive Sarilumab DL1 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 SC (Drug)
Sarilumab Dose Level 3 (DL3) IV - Part A
Participants will receive Sarilumab DL3 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 SC (Drug)
Sarilumab Dose Level 3 (DL3) IV - Part A
Participants will receive Sarilumab DL3 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 IV (Drug)
Sarilumab 200 mg Q2W SC - Part A
Participants will receive Sarilumab 200 mg Q2W SC on Day 1 every 2 weeks for 24 weeks.
干预措施: Sarilumab, SAR153191 SC (Drug)
Sarilumab Dose Level 1 (DL1) IV - Part A
Participants will receive Sarilumab DL1 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 IV (Drug)
Sarilumab Dose Level 2 (DL2) IV - Part A
Participants will receive Sarilumab DL2 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 SC (Drug)
Sarilumab Dose Level 2 (DL2) IV - Part A
Participants will receive Sarilumab DL2 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 IV (Drug)
Sarilumab Dose Level 4 (DL4) IV - Part A
Participants will receive Sarilumab DL4 IV. Participants continuing in the open label extension (OLE) arm will receive Sarilumab 200 mg SC Q2W for an additional 20 weeks.
干预措施: Sarilumab, SAR153191 SC (Drug)
Selected Sarilumab IV Dose - Part B
Participants will receive Sarilumab selected dose IV.
干预措施: Sarilumab, SAR153191 IV (Drug)
结局指标
主要结局
Part A: Assessment of Pharmacokinetic (PK) parameters of sarilumab in serum: area under the concentration-time curve [AUClast] for IV doses
时间窗: from Baseline up to Week 6
Area under the concentration versus time curve from time zero to time corresponding to the last measurable concentration, tlast.
Part A: Assessment of PK parameters of sarilumab in serum: maximum concentration [Cmax] for IV doses
时间窗: from Baseline up to Week 6
Maximum concentration observed.
Part B: Assessment of PK parameters of sarilumab in serum: plasma concentration at steady state (Ctrough ss)
时间窗: from Baseline up to Week 30
Concentration observed before treatment administration during repeated dosing at steady state.
次要结局
- Part A: Proportion of participants who experienced adverse events (AEs): treatment-emergent adverse events (TEAEs) up to the post-treatment EOS follow-up visit included(From Baseline up to Week 32)
- Part A: Proportion of participants who experienced potentially clinically significant abnormalities (PCSA) in clinical laboratory evaluations, vital signs, and electrocardiogram (ECG) parameters(From Baseline up to Week 32)
- Part A: Proportion of participants with injection site reactions (local tolerability assessments)(From Baseline up to Week 26)
- Part B: Assessment of PK parameters of sarilumab in serum: maximum peak plasma drug concentration at steady state (Cmax ss)(from Baseline up to Week 30)
- Part B: Area under the curve for the defined interval between doses (TAU) at steady state (AUC0-tau ss)(from Baseline up to Week 30)
- Part B: Proportion of participants who experienced adverse events (AEs): treatment-emergent adverse events (TEAEs) up to the post-treatment EOS follow-up visit included(From Baseline up to Week 30)
- Part B: Proportion of participants who experienced potentially clinically significant abnormalities (PCSA) in clinical laboratory test evaluations, vital signs, and electrocardiogram (ECG) parameters(From Baseline up to Week 30)
- Part B: Proportion of participants with injection site reactions (local tolerability assessments)(From Baseline up to Week 24)