Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Drug: PlaceboDrug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)
- Registration Number
- NCT03889639
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 2: Placebo Then SAR442168 15 mg Placebo 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. Cohort 2: Placebo Then SAR442168 30 mg Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 1: SAR442168 5 mg Then Placebo Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 2: Placebo Then SAR442168 5 mg SAR442168 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. Cohort 1: SAR442168 60 mg Then Placebo SAR442168 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. Cohort 2: Placebo Then SAR442168 15 mg Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 1: SAR442168 5 mg Then Placebo 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. Cohort 1: SAR442168 30 mg Then Placebo Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 1: SAR442168 60 mg Then Placebo Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 2: Placebo Then SAR442168 30 mg SAR442168 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. Cohort 1: SAR442168 15 mg Then Placebo 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. Cohort 1: SAR442168 15 mg Then Placebo Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 1: SAR442168 30 mg Then Placebo 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. Cohort 1: SAR442168 60 mg Then Placebo 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. Cohort 2: Placebo Then SAR442168 5 mg Placebo 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. Cohort 2: Placebo Then SAR442168 5 mg Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 2: Placebo Then SAR442168 30 mg Placebo 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. Cohort 2: Placebo Then SAR442168 60 mg Placebo 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. Cohort 2: Placebo Then SAR442168 60 mg Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) 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. Cohort 1: SAR442168 5 mg Then Placebo SAR442168 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. Cohort 1: SAR442168 15 mg Then Placebo SAR442168 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. Cohort 1: SAR442168 30 mg Then Placebo SAR442168 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. Cohort 2: Placebo Then SAR442168 15 mg SAR442168 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. Cohort 2: Placebo Then SAR442168 60 mg SAR442168 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.
- Primary Outcome Measures
Name Time Method Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (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 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).
- Secondary Outcome Measures
Name Time Method 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 new and enlarging T2 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).
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 AE was defined as any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug. SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs: AEs that developed, worsened, or became serious during on-treatment period (for this outcome measure defined as "SAR442168 treatment period" which was considered as Weeks 1 to 12 for Cohort 1 and Weeks 4 to 16 for Cohort 2).
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 Total number of 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).
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 Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with use of study drug. Serious AE (SAE) was defined as any untoward medical occurrence that, at any dose resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs were defined as AEs (serious/non-serious) that developed, worsened, or became serious during on-treatment period (for this outcome measure- "Weeks 1 to 4 period": time from 1st administration of study drug to Week 4). Cohorts 1 and 2 received SAR442168 and placebo for first 4 weeks, respectively.
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 Individual clinically relevant abnormalities was defined as potentially clinically significant abnormalities (PCSA) considered as SAEs or TEAEs leading to study treatment discontinuation or study discontinuation during the on-treatment period (time from first study drug administration until Week 16), considering all evaluations performed during the on-treatment period that included unscheduled or repeated evaluations.
Trial Locations
- Locations (48)
Investigational Site Number 8400005
🇺🇸Cullman, Alabama, United States
Investigational Site Number 8400002
🇺🇸Maitland, Florida, United States
Investigational Site Number 8400004
🇺🇸Sunrise, Florida, United States
Investigational Site Number 8400009
🇺🇸Tampa, Florida, United States
Investigational Site Number 8400007
🇺🇸Savannah, Georgia, United States
Investigational Site Number 8400001
🇺🇸Northbrook, Illinois, United States
Investigational Site Number 8400003
🇺🇸Knoxville, Tennessee, United States
Investigational Site Number 8400006
🇺🇸Westerville, Ohio, United States
Investigational Site Number 8400008
🇺🇸Dayton, Ohio, United States
Investigational Site Number 1240002
🇨🇦Gatineau, Canada
Investigational Site Number 1240001
🇨🇦Greenfield Park, Canada
Investigational Site Number 1240003
🇨🇦Vancouver, Canada
Investigational Site Number 2030007
🇨🇿Brno, Czechia
Investigational Site Number 2030004
🇨🇿Hradec Kralove, Czechia
Investigational Site Number 2030003
🇨🇿Jihlava, Czechia
Investigational Site Number 2030005
🇨🇿Ostrava - Poruba, Czechia
Investigational Site Number 2030006
🇨🇿Pardubice, Czechia
Investigational Site Number 2030001
🇨🇿Praha 2, Czechia
Investigational Site Number 2030002
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number 2330001
🇪🇪Tallinn, Estonia
Investigational Site Number 2500001
🇫🇷Nantes Cedex 1, France
Investigational Site Number 2500004
🇫🇷Nancy Cedex, France
Investigational Site Number 5280001
🇳🇱Amsterdam, Netherlands
Investigational Site Number 2500002
🇫🇷Strasbourg Cedex, France
Investigational Site Number 2500003
🇫🇷Toulouse Cedex 9, France
Investigational Site Number 5280002
🇳🇱Sittard-Geleen, Netherlands
Investigational Site Number 6430006
🇷🇺Kazan, Russian Federation
Investigational Site Number 6430003
🇷🇺Moscow, Russian Federation
Investigational Site Number 6430002
🇷🇺Moscow, Russian Federation
Investigational Site Number 6430001
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 6430005
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 6430004
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 7030001
🇸🇰Bratislava, Slovakia
Investigational Site Number 6430007
🇷🇺Tyumen, Russian Federation
Investigational Site Number 7030002
🇸🇰Martin, Slovakia
Investigational Site Number 7240006
🇪🇸Barakaldo, Spain
Investigational Site Number 7240001
🇪🇸Madrid, Spain
Investigational Site Number 7240004
🇪🇸Murcia, Spain
Investigational Site Number 7240002
🇪🇸Barcelona, Spain
Investigational Site Number 7240005
🇪🇸Salt, Spain
Investigational Site Number 7240003
🇪🇸Sevilla, Spain
Investigational Site Number 8040002
🇺🇦Chernivtsi, Ukraine
Investigational Site Number 8040005
🇺🇦Dnipro, Ukraine
Investigational Site Number 8040001
🇺🇦Lviv, Ukraine
Investigational Site Number 8040006
🇺🇦Lviv, Ukraine
Investigational Site Number 8040003
🇺🇦Vinnytsya, Ukraine
Investigational Site Number 8040009
🇺🇦Odesa, Ukraine
Investigational Site Number 8040007
🇺🇦Zhytomyr, Ukraine