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Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis

Primary Purpose

Relapsing Multiple Sclerosis

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tolebrutinib
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Participants must have completed treatment in the DRI15928 study
  • Female participants must continue to use an acceptable effective contraception method of birth control from inclusion and until the last dose of study drug, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. Menopause is defined as being amenorrheic for ≥12 months with plasma follicle stimulating hormone (FSH) level >30 UI/L.
  • The participant must have given written informed consent prior to undertaking any study related procedure.

Exclusion criteria:

  • The participant has a confirmed concomitant laboratory or ECG abnormality or medical condition deemed by the investigator incompatible with continuation of SAR442168 treatment.
  • The participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) between the last DRI15928 visit and the first treatment visit in the LTS16004 study.
  • The participant has received a non-study MS disease modifying treatment between the last IMP treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement of the Investigator may add unjustified risk to switching back and continuing treatment with SAR442168. Washout periods after treatment with non-study DMTs should be respected except for interferons or glatiramer acetate treatment.
  • The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes.

  • The participant is receiving anticoagulant/antiplatelet therapies, including:

    • Acetylsalicylic acid (aspirin)
    • Antiplatelet drugs (eg, clopidogrel)
    • Warfarin (vitamin K antagonist)
    • Heparin, including low molecular weight heparin (antithrombin agents)
    • Dabigatran (direct thrombin inhibitor)
    • Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors)

Note: All above drugs need to be stopped at least 5 half-lives before study drug administration except for aspirin, which needs to be stopped at least 8 days beforehand.

  • Prior/concurrent clinical study experience. The participant is taking part in another interventional clinical trial of another drug substance.
  • Uncooperative behavior or any condition that could make the participant potentially non-adherent with the study procedures
  • The participant is pregnant or is a breastfeeding woman.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sites / Locations

  • Investigational Site Number 8400005
  • Investigational Site Number 8400002
  • Investigational Site Number 8400009
  • Investigational Site Number 8400007
  • Investigational Site Number 8400001
  • Investigational Site Number 8400008
  • Investigational Site Number 8400006
  • Investigational Site Number 8400003
  • Investigational Site Number 1240001
  • Investigational Site Number 1240003
  • Investigational Site Number 2030007
  • Investigational Site Number 2030004
  • Investigational Site Number 2030003
  • Investigational Site Number 2030005
  • Investigational Site Number 2030006
  • Investigational Site Number 2030001
  • Investigational Site Number 2030002
  • Investigational Site Number 2330001
  • Investigational Site Number 2500004
  • Investigational Site Number 5280001
  • Investigational Site Number 6430006
  • Investigational Site Number 6430003
  • Investigational Site Number 6430001
  • Investigational Site Number 6430005
  • Investigational Site Number 6430007
  • Investigational Site Number 7240002
  • Investigational Site Number 7240001
  • Investigational Site Number 7240004
  • Investigational Site Number 7240005
  • Investigational Site Number 7240003
  • Investigational Site Number 8040002
  • Investigational Site Number 8040005
  • Investigational Site Number 8040001
  • Investigational Site Number 8040006
  • Investigational Site Number 8040009
  • Investigational Site Number 8040003
  • Investigational Site Number 8040007

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SAR442168

Arm Description

SAR442168 : Experimental - Part A: Double-blind period of continued treatment with the respective SAR442168 dose administered in the DRI15928 study until selection of Phase 3 dose. Part B: Open-label period of a single-group treatment with SAR442168 selected Phase 3 dose of 60 mg. All participants will be switched to this 60 mg dose.

Outcomes

Primary Outcome Measures

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants with Potentially Clinically Significant Abnormalities
Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs during the study period.

Secondary Outcome Measures

Number of new gadolinium (Gd)-enhancing T1 hyperintense lesions
New gadolinium (Gd)-enhancing T1 hyperintense lesions determined by brain Magnetic Resonance Imaging (MRI)
Number of new or enlarging T2 lesions
T2 lesions, a marker of inflammatory activity and brain tissue destruction in RMS will be evaluated by MRI
Total number of Gd-enhancing T1-hyperintense lesions
Total number of Gd-enhancing T1-hyperintense lesions
Number of participants wih relapse (Annualized Relapse rate)
Annualized Relapse rate is defined as the number of participants with relapse during the study period.
Change in Expanded Disability Status Scale (EDSS) from baseline over time
Standard EDSS assessments of neurological symptoms in each of 7 functional domains (visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral and bowel/bladder) will be performed. Ambulation will also be scored as part of the evaluation.

Full Information

First Posted
June 20, 2019
Last Updated
April 21, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT03996291
Brief Title
Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis
Official Title
Long-term Extension Safety and Efficacy Study of SAR442168 in Participants With Relapsing Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 23, 2019 (Actual)
Primary Completion Date
November 29, 2024 (Anticipated)
Study Completion Date
November 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Objective: To determine the long-term safety and tolerability of SAR442168 in RMS participants Secondary Objective: To evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods
Detailed Description
Approximately 62 months including the 8 weeks post-treatment visit

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR442168
Arm Type
Experimental
Arm Description
SAR442168 : Experimental - Part A: Double-blind period of continued treatment with the respective SAR442168 dose administered in the DRI15928 study until selection of Phase 3 dose. Part B: Open-label period of a single-group treatment with SAR442168 selected Phase 3 dose of 60 mg. All participants will be switched to this 60 mg dose.
Intervention Type
Drug
Intervention Name(s)
Tolebrutinib
Other Intervention Name(s)
SAR442168
Intervention Description
Pharmaceutical form: Film coated tablet Route of administration: Oral
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)
Title
Number of Participants with Potentially Clinically Significant Abnormalities
Description
Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs during the study period.
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)
Secondary Outcome Measure Information:
Title
Number of new gadolinium (Gd)-enhancing T1 hyperintense lesions
Description
New gadolinium (Gd)-enhancing T1 hyperintense lesions determined by brain Magnetic Resonance Imaging (MRI)
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)
Title
Number of new or enlarging T2 lesions
Description
T2 lesions, a marker of inflammatory activity and brain tissue destruction in RMS will be evaluated by MRI
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)
Title
Total number of Gd-enhancing T1-hyperintense lesions
Description
Total number of Gd-enhancing T1-hyperintense lesions
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)
Title
Number of participants wih relapse (Annualized Relapse rate)
Description
Annualized Relapse rate is defined as the number of participants with relapse during the study period.
Time Frame
Baseline to Month 60
Title
Change in Expanded Disability Status Scale (EDSS) from baseline over time
Description
Standard EDSS assessments of neurological symptoms in each of 7 functional domains (visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral and bowel/bladder) will be performed. Ambulation will also be scored as part of the evaluation.
Time Frame
Baseline to final follow-up visit ( Month 60 plus 8 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Participants must have completed treatment in the DRI15928 study Female participants must continue to use an acceptable effective contraception method of birth control from inclusion and until the last dose of study drug, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. Menopause is defined as being amenorrheic for ≥12 months with plasma follicle stimulating hormone (FSH) level >30 UI/L. The participant must have given written informed consent prior to undertaking any study related procedure. Exclusion criteria: The participant has a confirmed concomitant laboratory or ECG abnormality or medical condition deemed by the investigator incompatible with continuation of SAR442168 treatment. The participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) between the last DRI15928 visit and the first treatment visit in the LTS16004 study. The participant has received a non-study MS disease modifying treatment between the last IMP treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement of the Investigator may add unjustified risk to switching back and continuing treatment with SAR442168. Washout periods after treatment with non-study DMTs should be respected except for interferons or glatiramer acetate treatment. The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes. The participant is receiving anticoagulant/antiplatelet therapies, including: Acetylsalicylic acid (aspirin) Antiplatelet drugs (eg, clopidogrel) Warfarin (vitamin K antagonist) Heparin, including low molecular weight heparin (antithrombin agents) Dabigatran (direct thrombin inhibitor) Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors) Note: All above drugs need to be stopped at least 5 half-lives before study drug administration except for aspirin, which needs to be stopped at least 8 days beforehand. Prior/concurrent clinical study experience. The participant is taking part in another interventional clinical trial of another drug substance. Uncooperative behavior or any condition that could make the participant potentially non-adherent with the study procedures The participant is pregnant or is a breastfeeding woman. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400005
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35058
Country
United States
Facility Name
Investigational Site Number 8400002
City
Maitland
State/Province
Florida
ZIP/Postal Code
32761
Country
United States
Facility Name
Investigational Site Number 8400009
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Investigational Site Number 8400007
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31406
Country
United States
Facility Name
Investigational Site Number 8400001
City
Northbrook
State/Province
Illinois
ZIP/Postal Code
60062
Country
United States
Facility Name
Investigational Site Number 8400008
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Investigational Site Number 8400006
City
Westerville
State/Province
Ohio
ZIP/Postal Code
43081
Country
United States
Facility Name
Investigational Site Number 8400003
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Facility Name
Investigational Site Number 1240001
City
Greenfield Park
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
Investigational Site Number 1240003
City
Vancouver
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
Investigational Site Number 2030007
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Investigational Site Number 2030004
City
Hradec Kralove
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Investigational Site Number 2030003
City
Jihlava
ZIP/Postal Code
58633
Country
Czechia
Facility Name
Investigational Site Number 2030005
City
Ostrava - Poruba
ZIP/Postal Code
70852
Country
Czechia
Facility Name
Investigational Site Number 2030006
City
Pardubice
ZIP/Postal Code
53203
Country
Czechia
Facility Name
Investigational Site Number 2030001
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Investigational Site Number 2030002
City
Praha 5 - Motol
ZIP/Postal Code
15006
Country
Czechia
Facility Name
Investigational Site Number 2330001
City
Tallinn
ZIP/Postal Code
11315
Country
Estonia
Facility Name
Investigational Site Number 2500004
City
Nancy Cedex
ZIP/Postal Code
54035
Country
France
Facility Name
Investigational Site Number 5280001
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Investigational Site Number 6430006
City
Kazan
ZIP/Postal Code
420021
Country
Russian Federation
Facility Name
Investigational Site Number 6430003
City
Moscow
ZIP/Postal Code
125367
Country
Russian Federation
Facility Name
Investigational Site Number 6430001
City
Saint-Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
Facility Name
Investigational Site Number 6430005
City
St-Petersburg
ZIP/Postal Code
194044
Country
Russian Federation
Facility Name
Investigational Site Number 6430007
City
Tyumen
ZIP/Postal Code
625000
Country
Russian Federation
Facility Name
Investigational Site Number 7240002
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number 7240001
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Investigational Site Number 7240004
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Investigational Site Number 7240005
City
Salt
ZIP/Postal Code
17190
Country
Spain
Facility Name
Investigational Site Number 7240003
City
Sevilla
ZIP/Postal Code
41071
Country
Spain
Facility Name
Investigational Site Number 8040002
City
Chernivtsi
ZIP/Postal Code
58018
Country
Ukraine
Facility Name
Investigational Site Number 8040005
City
Dnipro
ZIP/Postal Code
49005
Country
Ukraine
Facility Name
Investigational Site Number 8040001
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
Investigational Site Number 8040006
City
Lviv
ZIP/Postal Code
79013
Country
Ukraine
Facility Name
Investigational Site Number 8040009
City
Odesa
ZIP/Postal Code
65025
Country
Ukraine
Facility Name
Investigational Site Number 8040003
City
Vinnytsya
ZIP/Postal Code
21005
Country
Ukraine
Facility Name
Investigational Site Number 8040007
City
Zhytomyr
ZIP/Postal Code
10002
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Learn more about this trial

Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis

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