A Phase 2b Dose-finding Study for SAR442168, a Bruton's Tyrosine Kinase Inhibitor, in Participants With Relapsing Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 130
- 试验地点
- 48
- 主要终点
- Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions
研究概览
简要总结
Primary Objective:
To determine the dose-response relationship for SAR442168 to reduce the number of new active brain lesions.
Secondary Objectives:
- To evaluate efficacy of SAR442168 on disease activity as assessed by imaging measures.
- To evaluate the safety and tolerability of SAR442168.
详细描述
The total study duration was 24 weeks which included a screening period of 4 weeks, a treatment period of 16 weeks, and a follow-up period of up to 4 weeks. Participants who completed the Week 16 visit were proposed to be enrolled in a long-term extension safety and efficacy study to assess safety, tolerability and efficacy of SAR442168.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: SAR442168 5 mg Then Placebo
Participants received SAR442168 5 milligrams (mg), orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 1: SAR442168 5 mg Then Placebo
Participants received SAR442168 5 milligrams (mg), orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 1: SAR442168 5 mg Then Placebo
Participants received SAR442168 5 milligrams (mg), orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 1: SAR442168 15 mg Then Placebo
Participants received SAR442168 15 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 1: SAR442168 15 mg Then Placebo
Participants received SAR442168 15 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 1: SAR442168 15 mg Then Placebo
Participants received SAR442168 15 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 1: SAR442168 30 mg Then Placebo
Participants received SAR442168 30 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 1: SAR442168 30 mg Then Placebo
Participants received SAR442168 30 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 1: SAR442168 30 mg Then Placebo
Participants received SAR442168 30 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 1: SAR442168 60 mg Then Placebo
Participants received SAR442168 60 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 1: SAR442168 60 mg Then Placebo
Participants received SAR442168 60 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 1: SAR442168 60 mg Then Placebo
Participants received SAR442168 60 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 2: Placebo Then SAR442168 5 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 5 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 2: Placebo Then SAR442168 5 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 5 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 2: Placebo Then SAR442168 5 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 5 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 2: Placebo Then SAR442168 15 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 15 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 2: Placebo Then SAR442168 15 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 15 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 2: Placebo Then SAR442168 15 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 15 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 2: Placebo Then SAR442168 30 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 30 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 2: Placebo Then SAR442168 30 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 30 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 2: Placebo Then SAR442168 30 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 30 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
Cohort 2: Placebo Then SAR442168 60 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 60 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: SAR442168 (Drug)
Cohort 2: Placebo Then SAR442168 60 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 60 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Placebo (Drug)
Cohort 2: Placebo Then SAR442168 60 mg
Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 60 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.
干预措施: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) (Drug)
结局指标
主要结局
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions
时间窗: After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants) and at Week 4 for Cohort 2 placebo
Number of new Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants). Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to collected during placebo administration in Cohort 1 (Weeks 12 to 16).
次要结局
- Number of New or Enlarging T2 Lesions(After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo)
- Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period(Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants)
- Total Number of Gd-enhancing T1-hyperintense Lesions(After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period(From Baseline up to Week 4)
- Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG)(Baseline up to Week 12 for Cohort 1 participants; Baseline up to Week 4 for Cohort 2 Placebo and from Weeks 4 to 16 for Cohort 2 SAR442168 receiving participants)